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250-510 exam Dumps Source : Administration of SymantecTM Data Loss(R) Prevention 10.5 - BETA
Test Code : 250-510
Test Name : Administration of SymantecTM Data Loss(R) Prevention 10.5 - BETA
Vendor Name : Symantec
: 196 Real Questions
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Symantec, the world’s main cyber protection company, announced email Fraud coverage, an automated solution that helps companies block fraudulent emails from achieving enterprises, guaranteeing comprehensive company attractiveness and sender have faith.
email Fraud insurance policy reduces workload for IT departments and eliminates the should manually manipulate e mail security configurations whereas combatting company email Compromise (BEC) attacks.
e mail is a vulnerable access element for hackers who're continuously constructing new and advanced recommendations to expose essential facts. As such BEC, or impersonation emails from relied on senders, are a big possibility to groups. in keeping with the FBI, BEC attacks grew 136 p.c over the past two years, with mentioned attacks totaling $12.5 billion.
Symantec e mail Fraud insurance policy takes a multi-layered method to stopping fraudulent emails that target personnel, companions and consumers, and maintaining brands’ reputations from hackers who impersonate enterprise management.
not best are e-mail threats expensive, but manually imposing e mail authentication requirements together with SPF, DKIM or DMARC can be time-consuming and require particularly technical elements to precisely establish third-birthday party electronic mail senders without false positives that block essential emails. email Fraud insurance policy eliminates the need for administrators to manually set and preserve email sender parameters, as an alternative e mail authentication requisites are met by means of automatic monitoring of accepted third-party senders.
“It’s now not convenient to find an answer that may stop e mail impersonation via DMARC, principally in a business world the place you have got diverse respectable senders for a site. Symantec email Fraud insurance plan is that solution,” stated James Charlton, IT safety manager at MS Amlin – global strong point Insurer and Reinsurer.
electronic mail Fraud insurance policy integrates with Symantec e-mail safety to guide electronic mail authentication specifications and help block platform threats on-premises or in the cloud, such as spam, malware, and phishing attacks. it may additionally integrate with Symantec electronic mail danger Isolation to lower the possibility of spear phishing, credential theft, account takeover, and ransomware assaults.
“Symantec is focused on delivering business cost to valued clientele via their built-in Cyber protection Platform. e-mail Fraud protection is an excellent addition to Symantec e-mail protection, guaranteeing corporations are fitted with an automated and comprehensive email safety answer,” noted Patrick Gardner, senior vp, e-mail security, Symantec. “Our intention is to give groups and IT departments time and cash again that can also be spent somewhere else in the corporation.”
MOUNTAIN VIEW, Calif.--(enterprise WIRE)--
e mail Fraud coverage now purchasable as a part of Symantec’s e mail safety answer and built-in Cyber protection Platform
Symantec Corp. (SYMC), the world’s leading cyber protection enterprise, these days announced email Fraud insurance policy, an automatic solution that helps organizations block fraudulent emails from accomplishing organisations, making certain complete brand recognition and sender have faith. electronic mail Fraud coverage vastly reduces workload for IT departments and eliminates the need to manually manage electronic mail protection configurations while combatting enterprise e-mail Compromise (BEC) assaults.
e mail is a vulnerable access aspect for hackers who are continually developing new and advanced concepts to show crucial facts. As such BEC, or impersonation emails from relied on senders, are an enormous possibility to companies. in response to the FBI, BEC assaults grew 136 percent during the last two years, with pronounced assaults totaling $12.5 billion. Symantec e mail Fraud coverage takes a multi-layered approach to stopping fraudulent emails that goal employees, companions and customers, and preserving manufacturers’ reputations from hackers who impersonate enterprise management.
not most effective are electronic mail threats expensive, however manually enforcing e-mail authentication requisites including SPF, DKIM or DMARC will also be time-drinking and require enormously technical supplies to accurately establish third-party electronic mail senders devoid of false positives that block essential emails. electronic mail Fraud protection eliminates the want for directors to manually set and retain email sender parameters, as a substitute electronic mail authentication requisites are met via computerized monitoring of accredited third-birthday party senders.
"or not it's no longer easy to find a solution that may cease e mail impersonation through DMARC, principally in a enterprise world the place you have got varied authentic senders for a site. Symantec electronic mail Fraud insurance plan is that solution,” said James Charlton, IT security supervisor at MS Amlin – global area of expertise Insurer and Reinsurer.
e mail Fraud insurance plan integrates with Symantec electronic mail protection to assist email authentication requisites and assist block platform threats on-premises or in the cloud, reminiscent of unsolicited mail, malware, and phishing assaults. it might additionally integrate with Symantec e-mail danger Isolation to cut the possibility of spear phishing, credential theft, account takeover, and ransomware assaults.
“Symantec is focused on providing business price to consumers via their built-in Cyber defense Platform. email Fraud insurance policy is a superb addition to Symantec email safety, making certain businesses are geared up with an automatic and complete electronic mail protection solution,” pointed out Patrick Gardner, senior vice president, e-mail protection, Symantec. “Our intention is to give groups and IT departments time and cash again that may also be spent elsewhere in the company.”
To study more about Symantec e mail Fraud insurance plan, seek advice from: https://www.symantec.com/blogs/product-insights/how-symantecs-e-mail-fraud-insurance policy-continues-your-company-safe-and-comfortable
Symantec business enterprise (SYMC), the world's main cyber security company, helps groups, governments and individuals cozy their most essential facts anywhere it lives. companies the world over appear to Symantec for strategic, built-in options to defend towards refined attacks across endpoints, cloud and infrastructure. Likewise, a world group of more than 50 million americans and households depend on Symantec's Norton and LifeLock product suites to give protection to their digital lives at home and across their devices. Symantec operates one of the crucial world's greatest civilian cyber intelligence networks, enabling it to peer and offer protection to in opposition t probably the most advanced threats. For additional info, please discuss with www.symantec.com or connect with us on fb, Twitter, and LinkedIn.
View supply edition on businesswire.com: https://www.businesswire.com/information/domestic/20190214005245/en/
Symantec Corp. SYMC, -0.sixty nine% the area’s leading cyber security business, introduced today that CRN®, a manufacturer of The Channel enterprise, has named Torjus Gylstorff, Symantec’s vice chairman, global partnersales, to its prestigious list of 2019 Channel Chiefs. The appropriate IT channel leaders covered on this checklist normally try to power increase and salary of their corporation through their channel companions.
each of the 2019 Channel Chiefs has validated awesome leadership, vision, and dedication to their channel partner classes. Channel Chief honorees are chosen by CRN’s editorial team of workers as a result of their knowledgeable achievements, standing in the industry, dedication to the channel companion community, and strategies for riding future increase and innovation.
Torjus Gylstorff leads Symantec's international sales strategy for distributors, cost-added resellers, and answer suppliers. all over his tenure, Symantec has emphasised its channel-first go-to-market method, demonstrating effective growth in channel participation rates throughout the globe. additionally, the group developed the Symantec secure One associate application to ensure a constant associate journey whereas providing access to supplies and advantages certain to each companions’ focus enviornment and company mannequin.
“The individuals on CRN’s 2019 Channel Chiefs list deserve special consciousness for their contribution and guide in the building of sturdy accomplice classes, creative company suggestions, and important influence to the normal health of the IT channel,” talked about Bob Skelley, CEO of The Channel enterprise. “We applaud each Channel Chief’s impressive record of accomplishments and seem forward to following their continued success.”
“As Symantec continues to innovate and expand their choices through their integrated Cyber protection Platform, companions stay a vital part of the way they simply reach, give protection to and service shoppers throughout markets,” mentioned Gylstorff. “I’m honored to be recognized by means of CRN for the astounding work that their team has finished to allow partners and drive sales around the world and across the product portfolio.”
The 2019 CRN Channel Chiefs checklist, together with the 50 Most Influential Channel Chiefs, is featured online at www.crn.com/channelchiefs and should seem in the February 2019 challenge of CRN.
Symantec employer SYMC, -0.sixty nine% the world's main cyber safety company, helps organizations, governments and individuals comfy their most crucial facts anywhere it lives. businesses the world over appear to Symantec for strategic, built-in solutions to shield against subtle attacks across endpoints, cloud and infrastructure. Likewise, a world neighborhood of greater than 50 million individuals and families depend on Symantec's Norton and LifeLock product suites to give protection to their digital lives at domestic and throughout their gadgets. Symantec operates one of the crucial world's largest civilian cyber intelligence networks, allowing it to see and give protection to against essentially the most superior threats. For additional information, please visitwww.symantec.comor connect with us onFacebook,Twitter, andLinkedIn.
in regards to the Channel enterprise
The Channel business makes it possible for leap forward IT channel efficiency with their dominant media, enticing routine, professional consulting and schooling and ingenious advertising and marketing features and platforms. because the channel catalyst, they connect and empower technology suppliers, answer providers and conclusion clients. Backed via greater than 30 years of unrivaled channel experience, they draw from their deep expertise to check imaginitive new options for ever-evolving challenges within the technology industry. www.thechannelco.com
follow The Channel business: Twitter, LinkedIn and facebook
Copyright ©2019. CRN is a registered trademark of The Channel business, LLC. All rights reserved.
View supply version on businesswire.com: https://www.businesswire.com/news/home/20190211005726/en/
source: Symantec Corp.
Nicole MurphySymantec650-527-7800Nicole_Murphy@symantec.comJennifer HoganThe Channel Companyjhogan@thechannelco.com
Copyright enterprise Wire 2019
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Everyone knows how mosquitos can wreck an end-of-summer picnic. But in some climates, these pesky intruders persist and carry a variety of detrimental diseases—some with no preventative vaccines or targeted therapies. One such passenger is dengue virus (DENV), which infects up to 400 million people each year and comes in several serotypes (1 to 4) and disease presentations—from mild infection to severe disease and sometimes death. But to treat or prevent dengue requires that they have a more complete picture of the disease pathology. Now, Modhiran et al. and Beatty et al. describe the results of in vitro and in vivo experiments that point to circulating dengue virus non-structural protein 1 (NS1) and the innate immune Toll-like receptor 4 (TLR4) as a focus for basic scientists as well as vaccine and drug developers.
DENV infection protects a patient from future reinfection with the same DENV serotype as well as producing temporary immune protection from severe dengue disease caused by a different DENV serotype. But unlike diamonds, this immune protection doesn’t last forever, and when the protected period passes, the patient becomes at increased risk of enhanced infection and progression to severe disease if he or she is infected with a second DENV serotype. This severe form of dengue infection is believed to result from immunopathogenic processes that induce cytokine storm and cause vascular leakage that leads to shock. Until now, no dengue viral proteins have been linked to vascular endothelium permeability (that is, vascular leakage).
Beatty et al. show that inoculation of mice with DENV NS1 protein alone induces both vascular leak and secretion of inflammatory cytokines and that administration of NS1 with a sublethal dose of DENV2 leads to lethal vascular leak syndrome. In human endothelial cell monolayers in culture, NS1 from any of the four DENV serotypes triggered endothelial barrier permeability. NS1’s pathogenic effects were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1 (in vivo and in vitro), and immunization of mice with NS1 protected against lethal DENV2 challenge.
In an independent study, Mondrian et al. explore the underlying of NS1’s effects. They show that highly purified NS1 acts as a pathogen-associated molecular pattern (PAMP) that activates mouse macrophages and human peripheral blood mononuclear cells (PBMCs) in culture via TLR4, resulting in release of inflammatory cytokines—an effect that was blocked by either a TLR4 antagonist or an anti-TLR4 antibody. Then, in an in vitro model of vascular leak, the authors found that NS1 fractured the integrity of endothelial cell monolayers through a TLR4-dependent pathway, a finding that was supported by the observation that a TLR4 antagonist quelled capillary leak in a mouse model of dengue virus infection.
Together, these new findings highlight NS1 as an instigator of dengue-associated vascular leak and thus pinpoint a potential target for dengue drugs and component for dengue vaccines.Abstract
The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients’ blood during acute infection; high levels of NS1 are associated with severe disease. They show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. They also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines.INTRODUCTION
Dengue virus (DENV) is a mosquito-borne flavivirus that is estimated to cause up to 390 million infections, 96 million cases of dengue, and ~500,000 hospitalizations annually (1). Infection with any of the four DENV serotypes (DENV1, DENV2, DENV3, and DENV4) results in a range of syndromes from inapparent infection to classic dengue fever (DF) to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), which is characterized by vascular leakage and shock (2). Most primary DENV infections caused by any of the four serotypes are asymptomatic or lead to the self-limiting but debilitating DF; however, secondary infections with a different (heterologous) DENV serotype can lead to increased risk of severe dengue (3). Immune responses after primary DENV infection lead to protective immunity to homologous secondary infection but may either protect against or cause increased disease severity in a subsequent DENV infection with a different serotype. The latter is thought to be mediated by serotype cross-reactive T cells or antibody-dependent enhancement (ADE), whereby cross-reactive antibodies that target viral structural proteins facilitate DENV infection of Fcγ receptor–bearing cells, leading to increased viral load (4, 5). ADE and cross-reactive T cells are thought to trigger an exaggerated and skewed immune response to a previously infecting serotype, resulting in a “cytokine storm”—rapid-onset, high-level production of proinflammatory cytokines, including tumor necrosis factor–α (TNF-α) and interleukin-6 (IL-6), in the blood that leads to endothelial permeability and vascular leak (6). However, the potential role of viral proteins in mediating vascular leakage has not been demonstrated.
The DENV 10.7-kb, positive-strand RNA genome encodes a polyprotein that is posttranslationally cleaved by host and viral proteases into three structural proteins [capsid, membrane, and envelope (E)] and seven nonstructural proteins. DENV nonstructural protein 1 (NS1) is a glycosylated 48-kD protein that plays a role in both viral replication and immune evasion (7, 8). NS1 is initially translated as a monomer that is glycosylated in the endoplasmic reticulum (ER) but rapidly forms a dimer that can have four fates: association with the viral replication complex on the surface of the ER membrane, plasma membrane association via a glycophosphatidylinositol linkage on infected cells, formation of a soluble lipophilic hexamer secreted by infected cells, or binding back of the hexameric NS1 to the surface of uninfected cells via glycosaminoglycan interactions (9, 10).
Secreted soluble DENV NS1 (sNS1) is found in patient serum during acute illness and is used as a diagnostic indicator of acute DENV infection. High levels of sNS1 are associated with increased disease severity, although it is unclear whether this measure has functional significance or is just a marker of higher viremia in severe cases. sNS1 can bind host complement components directly and inhibit complement activation in solution and on the cell surface, whereas sNS1-antibody complexes can consume complement in the context of secondary human DENV infection (11–14). Although sNS1 binds to endothelial cells (12), the functional consequences of this interaction for disease pathogenesis are poorly understood. Antibodies to NS1 cross-react with platelets, endothelial cells, and thrombin and are postulated to contribute to pathogenesis (15–17). However, vaccination with NS1 or passive transfer of monoclonal antibodies to NS1 (anti-NS1 mAbs) can at least partially protect against DENV infection in mice that are injected intracranially (18–21) or intraperitoneally (22) with DENV, indicating that anti-NS1 antibodies can be protective and not pathogenic (23). NS1 is considered a promising vaccine candidate (23–26) because it is highly conserved across DENV serotypes and because it should not generate disease-enhancing antibodies.
Although the levels of sNS1 correlate with disease severity, a direct role for NS1 in triggering endothelial disruption has not yet been established; therefore, they evaluated whether NS1 compromises endothelial cell integrity and contributes to vascular leakage in vitro and in vivo, respectively, and whether the immune response to NS1 after vaccination provides protection in a lethal mouse model of DENV vascular leak syndrome.RESULTS NS1 triggers vascular leak–mediated pathogenesis in vivo
We hypothesized that NS1 might elicit direct pathogenic effects in DENV disease and sought to test its effect in both the absence and presence of viral replication. For all experiments, they used commercially obtained recombinant NS1 produced in human embryonic kidney (HEK) 293 cells or in S2 cells. These NS1 preparations are highly purified (fig. S1A) and reported to be hexameric in structure; they confirmed that almost all the proteins are in the oligomeric form (fig. S1B). The NS1 preparation is reported to be endotoxin-free, which they confirmed using the Limulus Amebocyte Lysate assay [<0.1 EU/ml in 25 μg of NS1 from DENV1 to DENV4 NS1 (HEK 293) or DENV2 NS1 (S2)]. C57BL/6 mice deficient in the interferon-α/β receptor (Ifnar−/−) inoculated with DENV2 NS1 (10 or 20 mg/kg) in the absence of DENV infection exhibited morbidity on days 2 to 4 post-inoculation (p.i.), although they recovered by day 5 p.i. (fig. S2A). Moreover, 100% of naïve mice inoculated intravenously with DENV2 NS1 (10 mg/kg) combined with a sublethal dose [106 plaque-forming units (PFU)] of DENV2 strain D220 (hereafter referred to as DENV2) succumbed 3 to 4 days p.i., equivalent to mice receiving a lethal dose (107 PFU) of DENV2 (Fig. 1A). In contrast, mice receiving a sublethal dose of DENV2 alone or ovalbumin (OVA) (10 mg/kg) with a sublethal dose of DENV2 exhibited 100% survival and little morbidity. Mice injected with less DENV2 NS1 (5 mg/kg) combined with a sublethal dose of DENV2 all exhibited signs of disease starting day 2 p.i., and two of six mice succumbed on day 3 p.i. (Fig. 1A), suggesting a dose-dependent effect of NS1 in mediating severe dengue disease.Fig. 1. NS1 triggers vascular leak–mediated pathogenesis in vivo.
(A) Ifnar−/− mice were infected intravenously with a lethal dose of DENV2 (107 PFU) alone (n = 7), a sublethal dose of DENV2 (106 PFU) with DENV2 NS1 [5 mg/kg (n = 6) or 10 mg/kg (n = 7)], a sublethal dose of DENV2 with OVA [5 mg/kg (n = 6) or 10 mg/kg (n = 7)] as a negative control, or DENV2 NS1 (10 mg/kg) alone (n = 7). A Kaplan-Meier survival curve is shown, with data derived from two independent experiments. Mice given NS1 (10 mg/kg) alone or OVA (5 or 10 mg/kg) + 106 PFU of DENV2 exhibited statistically significant survival using a nonparametric Mantel-Cox log-rank test (P = 0.022) compared to mice given NS1 (10 mg/kg) + 106 PFU of DENV2. (B to D) Evans blue dye was injected intravenously into mice 3 days after treatment with DENV2 NS1 (10 mg/kg) (n = 7), DENV2 NS1 (20 mg/kg) (n = 4), OVA (10 mg/kg) (n = 6), NS1 (10 mg/kg) + 106 PFU of DENV2 (n = 4), OVA + 106 PFU of DENV2 (n = 4), or 106 (n = 4) or 107 PFU of DENV2 alone (n = 7), as indicated. The dye was allowed to circulate for 1 h before mice were euthanized, tissues were harvested, and Evans blue was extracted in formamide and quantified in (B) lung, (C) liver, and (D) small intestine tissue by measuring absorbance at OD610. In all tissues, the mice given NS1 (20 mg/kg) or NS1 (10 mg/kg) alone or NS1 (10 mg/kg) + 106 PFU of DENV2 had significantly higher levels of Evans blue than the OVA controls. (E) Ifnar−/− mice were administered DENV2 NS1 (10 mg/kg) or OVA (10 mg/kg) alone, NS1 or OVA (10 mg/kg) plus 106 PFU of DENV2, or 106 or 107 PFU of DENV2 alone, as indicated (n = 4 per group). Plasma was collected 3 days after treatment, and the levels of NS1 were measured by NS1-specific capture enzyme-linked immunosorbent assay (ELISA). (B to E) Data were derived from two independent experiments and were analyzed by nonparametric Mann-Whitney analysis. *P < 0.05; **P < 0.01.
We performed parallel experiments to measure vascular leakage as detected by tissue-associated Evans blue dye, which quantifies leakage out of the circulatory system when injected intravenously. They evaluated the vascular leakage on day 3 p.i. because this day was when they observed the greatest morbidity in the NS1-injected mice (fig. S2A). Mice receiving NS1 (10 mg/kg) plus a sublethal dose of DENV2 or a lethal dose of DENV2 displayed high levels of Evans blue dye in the lung, liver, spleen, and small and large intestines (Fig. 1, B to D, and fig. S2, B and C), indicating substantial vascular leakage. Mice receiving NS1 (10 or 20 mg/kg) alone contained significantly higher levels of Evans blue in all tissues than mice administered OVA as a negative control, whereas mice receiving sublethal doses of DENV2 (plus or minus OVA) had lower but measurable levels of Evans blue (Fig. 1, B to D, and fig. S2, B and C). These data demonstrate a role for NS1 alone in inducing vascular permeability in vivo.
In a separate set of mice, they evaluated the levels of circulating NS1, viremia, and selected cytokines in serum 3 days p.i., when maximum morbidity and mortality were observed, with or without NS1 or OVA as above. Injection of NS1 (10 mg/kg) alone resulted in ~1 μg/ml circulating NS1 in serum at day 3 p.i., only slightly higher than levels in mice infected with a lethal dose of DENV2 (Fig. 1E). Mice infected with a sublethal dose of DENV2 alone or combined with OVA (10 mg/kg) had ~0.25 μg/ml circulating NS1 at day 3 p.i., whereas mice infected with a sublethal dose of DENV2 and NS1 (10 mg/kg) yielded an average of ~2 μg/ml circulating NS1 at day 3 p.i. (Fig. 1E). They also evaluated the levels of NS1 every 12 h after inoculation with NS1 (10 mg/kg) and found that they decreased from ~15 μg/ml at 12 h p.i. to ~1 μg/ml at 72 h p.i. (fig. S2D); these levels are consistent with the range seen in humans with severe dengue (~1 to >10 μg/ml) (27, 28). Viremia levels were comparable between mice receiving NS1 plus a sublethal dose of DENV2 and mice infected with a lethal dose of DENV2, and both were 10-fold greater than viremia levels in OVA plus a sublethal dose of DENV2 or a sublethal dose of DENV2 alone (fig. S2E). With respect to cytokines often associated with DHF/DSS, they found that inoculation of NS1 alone or addition of NS1 to a sublethal dose of DENV2 significantly increased levels of TNF-α and IL-6 compared to negative controls, to levels similar to those observed in mice experiencing a lethal DENV2 infection (Fig. 2, A and B). In sum, the simultaneous injection of NS1 with a sublethal dose of DENV2 resulted in a lethal infection associated with vascular leakage, and NS1 alone increased vascular leakage in vivo. Furthermore, injection of NS1 in both the presence or absence of viral infection led to increased levels of critical inflammatory cytokines.Fig. 2. NS1 causes increased production of inflammatory cytokines in vivo in the presence or absence of DENV2.
Ifnar−/− mice were administered DENV2 NS1 (10 mg/kg) or OVA (10 mg/kg) alone, NS1 or OVA (10 mg/kg) plus 106 PFU of DENV2, or 106 or 107 PFU of DENV2 alone, as indicated (n = 4 per group). (A and B) Plasma was collected 3 days after treatment, and the levels of (A) IL-6 and (B) TNF-α were measured by ELISA. Mice given NS1 (10 mg/kg) + 106 PFU of DENV2 or NS1 (10 mg/kg) alone had significantly higher levels of both cytokines than controls receiving OVA. Data were derived from two independent experiments and were analyzed by nonparametric Mann-Whitney analysis. *P < 0.05.NS1 causes endothelial permeability in vitro
To directly evaluate a possible role for NS1 in triggering endothelial cell dysfunction, NS1 alone was incubated with cultures of a human pulmonary microvascular endothelial cell (HPMEC) line. HPMECs were grown on Transwell permeable membranes as a model of barrier function in vitro and incubated with DENV2 NS1 (0.2 to 20 μg/ml). Endothelial cell permeability was examined by measuring the transendothelial electrical resistance (TEER) of the HPMECs at different time points after treatment with NS1. TNF-α, known to induce endothelial barrier dysfunction, was used as a positive control and resulted in decreased TEER values (Fig. 3A). DENV2 NS1 induced a significant (P < 0.0001) dose-dependent increase in endothelial permeability compared to TEER baseline values exhibited by untreated controls and treatment with control protein (20 μg/ml OVA), starting ~2 h post-treatment (hpt) and persisting for 12 to 24 hpt depending on the dose (Fig. 3A and fig. S3A). Similar results were observed in primary human umbilical vein endothelial cells (HUVEC; fig. S3B). They then tested NS1 from DENV1, DENV2, DENV3, and DENV4 at 5 or 20 μg/ml on HPMEC monolayers (Fig. 3B and fig. S3C). NS1 from all four serotypes resulted in a significant (P < 0.0001) decrease in TEER; DENV1 and DENV2 NS1 caused the greatest reduction, from 3 to 13 hpt, whereas DENV3 and DENV4 NS1 displayed similar decreases from 9 to 13 hpt. In contrast, NS1 from West Nile virus (WNV), a closely related flavivirus that causes encephalitis but no systemic vascular leak, did not trigger reduction in TEER, nor did another DENV protein (E) when administered at the same concentration (Fig. 3B and fig. S1A). Thus, NS1 alone from all four DENV serotypes, but not WNV, can directly trigger increased endothelial cell permeability.Fig. 3. NS1 induces endothelial permeability in human pulmonary endothelial cells in vitro.
Confluent monolayers of HPMECs grown on Transwell inserts were incubated for 48 h with NS1, and TEER (ohm) was measured at indicated time points. Relative TEER (ratio of resistance values between experimental and untreated cells) was plotted. Data were normalized to inserts containing medium only. (A) Increasing concentrations of DENV2 NS1 (0.5 to 5 μg/ml) or TNF-α (1 ng/ml) were added to HPMEC monolayers, and TEER was measured at the indicated time points. (B) DENV1, DENV2, DENV3, DENV4 NS1, WNV NS1, or DENV2 E protein (5 μg/ml) was added to HPMEC monolayers, and TEER was analyzed at indicated time points. OVA (20 μg/ml) was used as a treatment control. Results are representative of three independent experiments using duplicate Transwells. Error bars indicate SEM. NS1, DENV2 NS1 (5 μg/ml).NS1 vaccination protects against lethal DENV–induced vascular leak syndrome
Given the ability of NS1 to induce vascular leak, they hypothesized that vaccination with NS1 might constitute a strategy for protecting against severe dengue disease. To investigate whether immune responses against NS1 could prevent lethal vascular leak–associated DENV disease, they immunized Ifnar−/− mice three times intraperitoneally with 20 μg of DENV2 NS1 and several different adjuvant systems over a 6-week period (days 1, 14, and 42) and challenged the mice with a lethal DENV2 infection 2 weeks after the last immunization (day 56). Mice immunized with DENV2 NS1 and monophosphoryl lipid A (MPLA)/AddaVax were completely protected against a lethal systemic challenge (Fig. 4A) and exhibited little morbidity. Similarly, NS1/MPLA/AddaVax-immunized mice were protected against antibody-enhanced lethal challenge with DENV2 (29, 30) (Fig. 4A). None of the OVA-immunized mice survived the high-dose or ADE lethal challenge. A low-dose (105 PFU) primary homologous infection with the parental DENV2 strain PL046 provided 100% protection against lethal challenge as a positive control (Fig. 4A). Thus, immune responses to adjuvanted NS1 protein alone were sufficient to provide complete protection, comparable to immunity induced by primary DENV infection. They then immunized mice with NS1, OVA, or DENV2 PL046, subjected them to lethal DENV2 challenge, and evaluated levels of NS1 in the serum. Sera from NS1-immune mice 3 days after the challenge contained almost no detectable NS1 compared to ~0.75 μg/ml in OVA-immunized mice, whereas NS1 levels in DENV2 PL046-immune mice were reduced to a lesser degree (~0.45 μg/ml) (Fig. 4B). NS1-immune and DENV-immune mice also displayed lower viremia in serum and lower viral load in bone marrow, spleen, and small intestine after challenge compared to OVA-immunized mice (Fig. 4, C and D, and fig. S4, A and B). These data suggest that the immune response to NS1 protected against mortality by greatly reducing circulating NS1 as well as decreasing the peripheral viral load.Fig. 4. NS1 vaccination protects against lethal DENV–induced vascular-leak syndrome.
(A) Mice were immunized intraperitoneally with 20 μg of DENV2 NS1 (n = 12) or OVA (n = 8) combined with MPLA/AddaVax adjuvants on days 0, 14, and 42 or infected with a sublethal dose (105 PFU) of DENV2 PL046 (n = 12) at day 0; on day 56, half were challenged intravenously with a lethal dose of 107 PFU of DENV2 and half with lethal antibody-enhanced DENV2 infection. A Kaplan-Meier survival curve is shown. Mice immunized with NS1 were significantly protected compared to OVA controls from both ADE (P = 0.003) and high-dose (hi-dose) (P = 0.001) lethal challenge. (B) NS1 levels in serum were measured by NS1-specific capture ELISA in NS1-immunized (n = 6) or OVA-immunized (n = 6) mice and DENV2 PL046–immune (n = 3) mice 3 days after DENV2 lethal challenge. Circulating NS1 was significantly higher in OVA-immunized compared to NS1-immunized mice after challenge; *P < 0.05; **P < 0.01. (C and D) The viral RNA copy number was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in (C) serum and (D) bone marrow 3 days post-lethal challenge. OVA-immunized mice (n = 6) had higher levels of viral RNA in both tissues compared to NS1-immunized mice (n = 6); *P < 0.05; **P < 0.01. The limit of detection is indicated by a dashed line. GAPDH, glyceraldehyde phosphate dehydrogenase. GE, genome equivalent. (E) Mice were immunized with 20 μg of NS1 from DENV1 (n = 8), DENV2 (n = 8), DENV3 (n = 5), or DENV4 (n = 5) or OVA (n = 10) with MPLA/AddaVax adjuvants as above, or 105 PFU of DENV2 PL046 (n = 10) at day 0 and then challenged intravenously on day 56 with a lethal dose of DENV2. Mice immunized with the four DENV NS1 serotypes separately were significantly protected against lethal challenge compared to OVA-immunized groups (DENV1, P = 0.002; DENV2, P = 0.008; DENV3, P = 0.004; DENV4, P = 0.014). Data were derived from three independent experiments.
Because relatively high homology exists in the amino acid sequence of NS1 within and across the four DENV serotypes (31), they examined whether immunization with NS1 could protect against a heterologous, lethal DENV infection. Mice were immunized as above with DENV1, DENV2, DENV3, or DENV4 NS1, challenged 2 weeks after the third immunization with a lethal dose of DENV2, and monitored for morbidity and mortality. As expected, DENV2 NS1 provided 100% protection against lethal homologous DENV2 challenge (Fig. 4E). Immunization with DENV1 NS1 provided 75% protection, and DENV3 or DENV4 NS1 provided 60% protection against DENV2 lethal challenge (Fig. 4E), demonstrating sufficient immune cross-reactivity to NS1 epitopes to provide partial protection across serotypes. Serum was obtained from mice 1 week after the third immunization with NS1 or OVA, which coincided with 7 weeks after DENV2 PL046 primary infection. They tested the prechallenge immune serum by ELISA for reactivity to NS1 of all four DENV serotypes (fig. S5). DENV NS1-immune sera bound strongly to NS1 from the homologous serotype and also exhibited substantial cross-reactivity to NS1 from the other three serotypes. In addition, the level of anti-NS1 antibody binding and serotype cross-reactivity was greater in NS1-immunized mice than in natural infection with the different DENV serotypes (fig. S5).NS1-immune serum and anti-NS1 mAbs block NS1-induced vascular leak
To determine whether antibodies from NS1-immunized mice could prevent the direct effect of NS1 on endothelial permeability, they tested NS1- or OVA-immune sera from vaccinated mice on HPMEC monolayers using the TEER assay. Intact NS1-immune sera inhibited the NS1-induced decrease in TEER, whereas OVA-immune sera provided no inhibition (Fig. 5A). Heat-inactivated NS1-immune sera also inhibited the NS1-induced decrease in TEER, demonstrating that the inhibition was not dependent on complement. Sera from DENV2 PL046-immune mice partially inhibited the reduction in TEER, consistent with the lower level of anti-NS1 antibodies observed in DENV2-immune sera compared to the level in NS1-immune sera (fig. S5). To further confirm the specificity of the antibody-mediated blocking of NS1 function in vitro, a panel of anti-NS1 mAbs was evaluated, and several anti-NS1 mAbs (for example, 2B7 and 1H7.4) were shown to inhibit the NS1-induced decrease in TEER (Fig. 5B). Several other anti-NS1 mAbs (for example, 2E9.E2) did not inhibit the reduction in TEER (Fig. 5B), demonstrating that blocking certain but not all epitopes leads to the loss of NS1 disruption of endothelial integrity. As expected, mAbs directed to another DENV protein, E (for example, 3H5), did not block NS1 function in the TEER assay, nor did the anti-NS1 mAbs alone have any effect on endothelial permeability (Fig. 5B).Fig. 5. NS1-immune serum and anti-NS1 mAbs block NS1-induced endothelial permeability in vitro.
(A) Monolayers of HPMECs grown on Transwell inserts were incubated for 48 h with both NS1 (5 μg/ml) and anti-NS1 serum (1:10 dilution), NS1 alone, or anti-NS1 serum alone, and TEER (ohm) was measured at indicated time points. OVA (5 μg/ml) was used as a protein control. Anti-OVA and anti-DENV2 PL046 sera were also included as controls. Results are representative of two independent experiments with duplicate Transwells. (B) Monolayers of HPMECs grown on Transwell inserts were incubated for 48 h with both NS1 (5 μg/ml) and NS1-specific mAbs (10 μg/ml) or either NS1 or anti-NS1 mAbs alone, and TEER (ohm) was measured at indicated time points. A mAb specific to DENV E protein (3H5) was used as an isotype control. Results are representative of three experiments, each with duplicate Transwells. Error bars indicate SEM.
To investigate the role of anti-NS1 antibodies in the protective immunity observed against NS1 toxicity in vivo, they passively transferred sera from NS1- or OVA-immunized mice (both in combination with MPLA/AddaVax) concurrently with a lethal challenge of NS1 plus a sublethal dose of DENV2. The passive transfer of 300 μl of anti–NS1-immune serum provided 100% protection from lethality, whereas mice receiving 300 μl of anti-OVA sera succumbed (Fig. 6A). Therefore, antibodies from NS1-vaccinated mice were sufficient to inhibit NS1-mediated toxicity, suggesting that anti-NS1 antibodies provide a critical component of immune protection against lethal DENV2 challenge observed in NS1-vaccinated mice.Fig. 6. NS1-immune serum and anti-NS1 mAb block NS1-induced lethality in vivo.
(A) Pooled serum (300 μl) from NS1-immunized (n = 7), OVA-immunized (n = 7), or DENV2 PL046–immune (n = 4) mice was transferred intraperitoneally to naïve Ifnar−/− mice before intravenous injection of NS1 (10 mg/kg) + 106 PFU of DENV2. Anti-NS1 or anti-OVA serum was transferred to naïve mice before injection of OVA (10 mg/kg) + 106 PFU of DENV2 (n = 4 per group) as controls (ctrl). Mice were followed for survival for 14 days p.i. Mice administered NS1-immune serum followed by NS1 + 106 PFU of DENV2 were significantly protected (P = 0.014) against lethality compared to mice given OVA-immune serum (n = 7), using the log-rank Mantel-Cox test. Data were derived from two independent experiments. (B) Ifnar−/− mice were infected intravenously with 107 PFU of DENV2 alone (n = 3), 106 PFU of DENV2 alone (n = 3), 106 PFU of DENV2 with DENV2 NS1 (10 mg/kg), or 106 PFU of DENV2 with OVA (10 mg/kg), as indicated. Mice injected with DENV2 combined with DENV2 NS1 or OVA were concomitantly injected intraperitoneally with 200 μg of isotype control mAb or anti-NS1 mAb (1H7.4) (n = 4 for all groups). Kaplan-Meier survival curves are shown, where mice were monitored for morbidity and survival for 10 days p.i. Mice given anti-NS1 mAbs were significantly protected (P = 0.0069) against lethality compared to mice given the isotype control mAbs by log-rank Mantel-Cox test.
Finally, they tested the ability of an anti-NS1 mAb that blocked TEER function in vitro (Fig. 5B) to protect against NS1-induced toxicity in vivo. The anti-NS1 mAb was administered to mice immediately after inoculation with a sublethal viral dose plus NS1 (10 mg/kg), and the mice were monitored for morbidity and mortality for 10 days. Mice receiving the lethal virus inoculum as a positive control and the mice receiving a sublethal viral dose plus NS1 (10 mg/kg) and the isotype control succumbed to the vascular leak disease; however, the mice receiving the sublethal viral dose plus NS1 (10 mg/kg) and the anti-NS1 mAb demonstrated 100% survival (Fig. 6B). Therefore, both polyclonal and monoclonal anti-NS1 antibodies can inhibit lethal vascular permeability in vivo and can block the ability of NS1 to trigger endothelial cell dysfunction in vitro.DISCUSSION
We have established that DENV NS1 causes vascular leak in vivo and induces increased permeability of human endothelial cells in vitro, both of which can be specifically blocked with NS1-immune polyclonal mouse sera or anti-NS1 mAbs. These results suggest that NS1 can cause endothelial dysfunction leading to vascular leakage during severe dengue disease. In addition, they demonstrated that immune responses elicited by vaccination with DENV2 NS1 protect against lethal challenge with high-dose or antibody-enhanced DENV2 infection, comparable to immunization with a primary sublethal DENV2 infection. Furthermore, vaccination with DENV1, DENV3, or DENV4 NS1 provided substantial protection against a heterologous DENV2 lethal challenge. Their findings, along with those in the accompanying paper by Modhiran et al. (32), add an important and previously overlooked component to the induction of vascular leak in severe dengue.
NS1 levels have been shown to correlate with disease severity (11, 28), and although NS1 antigenemia peaks concurrently with viremia early in disease, cumulative effects of NS1 on the endothelium might occur after several days of antigenemia, during the “critical phase” on days 4 to 6 post-symptom onset when hypovolemic shock is observed. This would be consistent with their finding that mice displayed the greatest vascular leak and morbidity 3 days after injection with NS1 alone and experienced the most severe disease 3 days after inoculation with NS1 combined with a sublethal dose of DENV. They found evidence of vascular leak in the lung, liver, spleen, and lymph nodes of mice, which parallels the finding that most of the histopathological damage identified in fatal human cases of dengue disease occurs in these tissues as well (33, 34). In terms of the physiological relevance of their findings, the in vitro and in vivo effects of NS1 occurred at concentrations similar to those reported in patients with DHF/DSS (27, 28). They also observed a correlation between the amount of circulating NS1, the degree of vascular leak, and production of inflammatory cytokines (IL-6 and TNF-α) in vivo. This is consistent with NS1 triggering increased production of vasoactive cytokines by monocytes and macrophages, as shown in the accompanying paper (32). Finally, they studied the effects of NS1 on human endothelial cell monolayers (HPMECs and HUVECs) and demonstrated that DENV, but not WNV, NS1 can disrupt endothelial cell permeability in a dose- and time-dependent manner. These in vitro results indicate that NS1 can act directly on the endothelial barrier to increase vascular permeability. These findings are consistent with those of Modhiran et al. (32), which showed that NS1 triggers endothelial permeability directly in human dermal microvascular endothelial cells within several hours of addition. Several possible mechanisms could explain the direct contribution of NS1 to vascular leak, including disruption of components of the endothelial glycocalyx layer and extracellular matrix and mislocalization or degradation of intercellular-junction proteins triggered by activation of intracellular signaling pathways (35, 36).
We show here that vaccination with NS1 protects against homologous and heterologous lethal challenge in Ifnar−/− mice, currently the in vivo model that best mimics features of severe human dengue (30). Previous studies using intracranial challenge demonstrated that immunization with DENV2 NS1 protected against homologous but not heterologous DENV serotypes (18). Earlier work also demonstrated that the passive transfer of NS1-specific mouse polyclonal antibodies or mAbs protected against intracranial homologous challenge with DENV2 (20, 21). More recent work has shown that an NS1 DNA vaccine as well as NS1 combined with a heat-labile toxin adjuvant can protect against intracranial challenge (23, 25, 26) in BALB/c mice. Their data show that vaccination with NS1 protects against lethal DENV–induced vascular leakage syndrome in mice and that anti–NS1-immune sera or anti-NS1 mAbs can prevent NS1-mediated vascular leakage both in vivo and in vitro. The antibody-derived immunity to NS1 could be mediated via an Fc-dependent pathway, complement-dependent pathways (37), or inhibition of the pathogenic effects of NS1. They suggest that antibodies to NS1 generated from vaccination can increase virus clearance as well as neutralize the vasoactive effects of NS1. Together, their data indicate that immunization with NS1 could provide critical protection against severe DENV disease without the risk of ADE and argue for the inclusion of DENV NS1 in dengue vaccines.
Although anti-NS1 antibodies can have a potential pathogenic effect because of cross-reactivity with human endothelial cells, platelets, or thrombin (15–17), they observed a protective rather than a pathogenic effect of anti-NS1 polyclonal antibodies or mAbs on endothelial cells. Heat-inactivated anti-NS1 sera lacking active complement components blocked NS1-mediated endothelial permeability, as did anti-NS1 mAbs added to HPMECs in the absence of complement. Their results demonstrate that DENV NS1 has a direct effect on endothelial cells and suggest that NS1 triggers vascular leakage in the absence of antibodies or complement. Finally, although antibodies to NS1 are reported more frequently after secondary DENV infection (38), it is possible that the repertoire of anti-NS1 antibodies and the amount of free NS1 (27, 28) may differ in patients who develop severe as compared to mild disease, a topic of future investigation.
In addition, they found that exogenous NS1 resulted in increased viral burden in vivo, which may also exacerbate disease. This is consistent with data showing increased viral output in DENV-infected cells exposed to exogenous NS1 (39). It also could result from the ability of NS1 to antagonize activation of complement pathways (8, 13), which can directly neutralize DENV in plasma (13, 14, 40) and control virus replication in vivo. They also noted that mice receiving a lethal dose of DENV2 alone displayed high levels of vascular leakage and inflammatory cytokines with only a partial increase in circulating NS1. This suggests that the increase in vascular leakage leading to mortality in the high-dose infection with DENV2 is partially attributable to virus-induced damage in addition to the pathogenic effects of NS1. This is consistent with a report by Watanabe et al. (41), which demonstrated differences among DENV2 strains in relation to mortality that were independent of the NS1 levels in a mouse model of DENV infection. It is also possible that strain-related differences in NS1 can modulate the pathogenic properties of NS1.
One of the limitations of this study was their ability to explore different kinetics of NS1 delivery in vivo. They delivered the NS1 in vivo in a single dose, which resulted in circulating levels initially 15 μg/ml at 12 h (on the high end of what has been seen in humans) that decrease to ~1 μg/ml at 72 h (more often the range seen in severe dengue cases); the rapid decline in NS1 levels may be attributable to protein degradation or clearance from the bloodstream. However, another paper that examined levels of NS1 in a mouse model of DENV2 infection reported circulating levels of NS1 in mice of 8 to 30 μg/ml (41). It will be interesting to explore different kinetics of delivery of NS1 in vivo. This study was also limited by their ability to differentiate, in the mouse model, between NS1 triggering endothelial permeability directly versus NS1 triggering mediators that may be acting on endothelial cells. Evaluating the precise role of signaling molecules and inflammatory mediators, including cytokines, in the mechanisms of NS1-induced vascular leak in vivo requires study in genetically deficient mice and the use of various inhibitors and/or antibodies; these studies are currently underway. In separate in vitro experiments, they have identified cytokine-independent, endothelial cell–intrinsic mechanisms through which NS1 leads to increased endothelial permeability, in addition to the cytokine-dependent pathways triggered by NS1 described by Modhiran et al. (32).
To date, the dominant theory to explain dengue shock invokes immunopathogenic processes thought to lead to endothelial dysfunction; here, they propose that DENV NS1 protein by itself is a key component in triggering the severe vascular leakage associated with life-threatening dengue. This work opens the door to evaluating potential drug therapeutics that can inhibit NS1-mediated disease. Likewise, their NS1 vaccination data showing protection against DENV lethal vascular leak syndrome points to the importance of including NS1 in dengue vaccine formulations.MATERIALS AND METHODS Study design
We designed these studies to show that DENV NS1 plays a role in causing vascular leakage and that immunization with NS1 could prevent DENV-induced systemic disease. They first showed that recombinant NS1 as a vaccine could protect against lethal DENV–induced vascular leak syndrome and then followed this with studies of NS1 alone or NS1 combined with a sublethal DENV infection to characterize disease due to increased levels of NS1. Mice infected with DENV with and without NS1 were evaluated on a morbidity scale from 1 to 5 (30). Mice were monitored every 12 h after infection, followed every 6 h when displaying a score of >3, and euthanized immediately when they became moribund (score of 5). NS1 immunization experiments included negative controls consisting of OVA-immunized or unimmunized mice that were not protected and DENV2 PL046-immunized mice as positive controls that were protected against lethal challenge. In NS1 vascular leak experiments, OVA-injected mice were used as negative controls in comparison to NS1-injected mice, and sublethal DENV infection plus OVA was included as a negative control compared to sublethal DENV infection plus NS1. Mouse experiments testing mortality or protection from lethal DENV challenge had endpoints 10 days after infection, and no NS1-immunized, NS1-injected, or DENV-infected mice were excluded from the study. Mouse experiments were performed in duplicate, with numbers totaling four or greater in each group. They then hypothesized that DENV NS1 directly induces endothelial permeability and used in vitro TEER experiments with cultured human endothelial cell lines to evaluate this effect. Each TEER experiment was performed two to three times, with each condition including two replicate wells that were each read twice. Each experiment contained the following controls: (i) Transwell inserts containing only medium to determine transient resistance values of the permeable membrane, (ii) Transwell inserts with cultured human endothelial cells to obtain resistance values of the endothelial cell monolayer alone, and (iii) a positive control consisting of vasoactive molecules such as TNF-α, which is known to increase endothelial permeability. In addition, as an irrelevant protein control, OVA was included in each experiment. For the protection experiments using sera obtained from NS1-vaccinated mice or anti-NS1 mAbs, Transwells containing only sera or anti-NS1 mAbs were included to exclude any effect on endothelial permeability induced by these components. TEER values were collected every 2 h for 12 h and at 24 h, then the medium was replaced to reestablish the integrity of the monolayer, and the TEER values were read at 26 and 48 h. No blinding or randomization was performed for either the mouse studies or the TEER experiments.Mice
Six- to eight-week old Ifnar−/− C57BL/6 mice were bred and maintained under specific pathogen–free conditions at the University of California, Berkeley, Animal Facility. Experiments were performed strictly following guidelines of the American Veterinary Medical Association and the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The Animal Care and Use Committee of the University of California, Berkeley, approved all experiments (protocol R252-1012B).Cell cultures and viruses
All viruses were propagated in the Aedes albopictus C6/36 cell line [American Type Culture Collection (ATCC)] and titered by plaque assay on baby hamster kidney cells (BHK21, clone 15). DENV2 PL046 was obtained originally from H.-Y. Lei (National Cheng Kung University, Taiwan). DENV2 D220 was produced in their laboratory from the parental strain DENV2 PL046 (42). An HPMEC line (HPMEC.ST1.6R) was donated by J. C. Kirkpatrick (Institute of Pathology, Johannes Gutenberg University, Germany), propagated (passages 5 to 8), and maintained at 37°C in humidified air with 5% CO2 in endothelial cell basal medium-2 supplemented with growth factors, antibiotics, and fetal bovine serum as per the manufacturer’s specifications (Clonetics, Lonza). HUVECs (passage 3) were donated by M. Lodoen (University of California, Irvine) and maintained as described above.Recombinant NS1 proteins and anti-NS1 mAbs
Recombinant NS1 proteins from DENV1, DENV2, DENV3, and DENV4 and WNV, greater than 95% purity and certified to be free of endotoxin contaminants, were produced by Native Antigen in HEK 293 cells; recombinant DENV2 NS1 produced in S2 cells was obtained from Merck. The recombinant DENV2 envelope (recE), expressed in a baculovirus expression vector system (GenScript) using High Five insect cells, was purified by an immune-affinity protein G column coupled to 4G2 (anti-E mAb). The NS1 and recE working stocks were also tested using the Endpoint Chromogenic Limulus Amebocyte Lysate (LAL) QCL-1000TM kit (Lonza) and confirmed to be bacterial endotoxin-free (<0.1 EU/ml per 25 μg of protein). Anti-NS1 mAbs were obtained as follows: 2B7 and 2E9.E2 were generated in the Harris laboratory (P.R.B. and E.H., unpublished), and 1H7.4 was a gift from P. Young (University of Queensland, Brisbane, Australia). mAb 3H5 (anti-DENV2 E) was obtained from ATCC. Hybridomas were propagated in CELLine culture flasks (Sigma); supernatants were collected, and the mAbs were affinity-purified using a Protein G Sepharose column. The mAbs were eluted from the column, concentrated, sterile-filtered, and titered before use.Mouse experiments of NS1-induced vascular leak and NS1 vaccination
For studies of NS1-induced vascular leak, Ifnar−/− mice were injected intravenously with NS1 (5 to 20 μg/kg) or OVA protein (10 μg/kg) alone or NS1 (5 to 10 μg/kg) or OVA (10 μg/kg) in combination with a sublethal dose of 106 PFU of DENV2 D220. Separate groups of mice were administered 106 PFU of DENV2 D220 alone as a sublethal control or 107 PFU of DENV2 D220 as a lethal control. Mice were observed every 12 h for morbidity using a scoring system on a scale of 1 to 5 as follows: 1 = healthy; 2 = ruffled fur and mild signs of lethargy; 3 = hunched posture, ruffled fur, and intermediate level of lethargy and failure to groom; 4 = very lethargic, limited mobility, ruffled fur, and hunched posture; and 5 = moribund with limited to no mobility and inability to reach food or water. Mice were euthanized immediately when they became moribund. For vascular leak studies and measurement of cytokines and levels of sNS1 and viral RNA, mice were euthanized 72 h after injection, blood was collected via cardiac puncture, and tissues were harvested. For mortality studies, mice were monitored for 10 days after injection. For vaccination studies, Ifnar−/− mice were injected intraperitoneally three times (days 0, 14, and 42) with 20 μg of NS1 or 20 μg of OVA with 1 μg of MPLA (InvivoGen) and AddaVax (0.5% sorbitan trioleate, 5% squalene, and 0.5% Tween 80 in 10 mM sodium citrate buffer; InvivoGen). Two weeks after the third immunization (day 56), mice were challenged with 107 PFU of DENV2 D220 intravenously or 5 μg of 4G2 (anti-E mAb) 24 h before 105 PFU of D220 (ADE). To test the effects of the anti–NS1-immune serum on NS1-induced vascular leak, Ifnar−/− mice were injected with 10 μg of NS1 or 10 μg of OVA in combination with 106 PFU of DENV2 D220, immediately administered 300 μl of polyclonal anti-NS1, anti-OVA, or anti–PL046-immune serum intraperitoneally, and then followed for morbidity and mortality for 10 days. The immune serum used for passive transfer was collected from NS1- or OVA-immunized mice or DENV PL046–infected mice 6 weeks after initial immunization or infection. To test the effects of anti-NS1 mAb on NS1-induced vascular leak, Ifnar−/− mice were injected with 10 μg of NS1 or 10 μg of OVA in combination with 106 PFU of DENV2 D220, immediately given 200 μg of anti-NS1 mAb (1H7.4) or isotype control antibody intraperitoneally, and then followed for morbidity and mortality for 10 days. Separate groups of mice were given 106 PFU of DENV2 D220 alone as a sublethal control or 107 PFU of DENV2 D220 as a lethal control.Enzyme-linked immunosorbent assays
Serum was collected 3 days after the intravenous injection of NS1 with or without DENV infection. Serum was analyzed by NS1-specific capture ELISA using mAb 7E11 (5 μg/ml; a gift from R. Putnak, Walter Reed Army Institute of Research) as a coating antibody, 50 μl of a 1:100 dilution of each mouse serum sample, followed by detection using 100 μl of a biotinylated NS1-specific mAb, 2B7 (4 μg/ml) (P.R.B. and E.H., unpublished). A standard curve of NS1 (7 to 2000 ng/ml) was run in parallel to quantify NS1 concentration in all samples. Absorbance [optical density at 405 nm (OD405)] was measured using an Applied Biosystems 7200 microplate reader. To determine levels of NS1-specific antibodies in immunized mice before challenge, serum was obtained 1 week after the third immunization via submandibular bleed. For the ELISA, 50 μl of NS1 (0.5 μg/ml) was coated onto a Nunc Immulon polystyrene plate; after blocking with 5% nonfat dry milk in phosphate-buffered saline (PBS) + 0.05% Tween 20 (PBS-T), 50 μl of a 1:100 dilution of each test serum was added and incubated for 24 h. After washing with PBS-T, biotinylated goat anti-mouse immunoglobulin G (Jackson ImmunoResearch) was added, followed by washing and addition of streptavidin–alkaline phosphatase (Life Technologies) and para-Nitrophenylphosphate (Sigma-Aldrich) substrate, which was read at OD405 as above. Capture ELISAs were performed to quantitate the levels of TNF-α or IL-6 in citrated plasma. Mouse TNF-α and IL-6 ELISA Ready-SET-Go! kits (eBioscience) were used according to the manufacturer’s instructions. The OD405 of each sample was measured, and cytokine levels in serum were expressed in picograms per milliliter.Quantitation of virus by qRT-PCR
Samples of all tissues were stored in RNA later (Ambion), and RNA was extracted using an RNeasy Mini kit (Qiagen). Serum was generated from whole blood by centrifugation, and RNA was extracted using a QIAamp Viral Recovery RNA kit (Qiagen). Serum viremia levels and tissue viral load were measured by qRT-PCR as described previously (29). Viral load was expressed as either glyceraldehyde phosphate dehydrogenase in genome equivalents per microgram (tissue) or genome equivalents per millilter (serum).Quantitation of Evans blue vascular leakage
Vascular leakage was quantified by Evans blue dye as previously described (42). Briefly, 200 μl of 0.5% Evans blue dye was injected intravenously 3 days after treatment and allowed to circulate for 1 h before mice were euthanized and cardiac puncture was performed. Tissues were collected in preweighed tubes containing 1 ml of formamide and incubated at 37°C and 5% CO2 for 24 h. Evans blue concentration in extracts was quantified by measuring OD610 in samples and comparing to a standard curve. Data were expressed as nanograms of Evans blue dye per milligram of tissue weight.Transendothelial electrical resistance
To evaluate the effect of sNS1 on the integrity of the endothelium, HPMEC or HUVEC monolayers grown on a 24-well Transwell polycarbonate membrane system (Transwell permeable support, 0.4 μM, 6.5-mm insert; Corning Inc.) were incubated with NS1 (0.2 to 20 μg/ml) or OVA (1 to 20 μg/ml) as a negative control. Endothelial permeability was evaluated by measuring TEER in ohms at sequential 2-h time points after the addition of test proteins. TEER was measured using an epithelial voltohmmeter with “chopstick” electrodes (World Precision Instruments). Transwell inserts containing untreated HPMEC cells were used as a negative control, and inserts with medium alone were used for blank resistance measurements. Relative TEER was expressed as the ratio of resistance value as follows: [ohm (experimental condition) − ohm (medium alone)]/[ohm (nontreated endothelial cells) − ohm (medium alone)]. After 24 h of treatment, 50% of upper and lower chamber media was replaced by fresh endothelial cell medium.Statistical analysis
Statistical analysis was performed using GraphPad Prism 6 software, and all graphs were generated using Prism 6. Comparison between ELISA and qRT-PCR titers was conducted using a nonparametric Mann-Whitney test. Comparison of survival rates was conducted using a nonparametric log-rank (Mantel-Cox) test and graphed as Kaplan-Meier survival curves. For TEER experiments, statistical significance was determined using a two-way analysis of variance (ANOVA), and differences in treatment were considered significant for P values <0.05.SUPPLEMENTARY MATERIALS
Fig. S1. Recombinant NS1 from DENV1, DENV2, DENV3, DENV4, and WNV is highly purified and oligomeric.
Fig. S2. Morbidity and vascular leakage are induced by NS1.
Fig. S3. NS1 increases endothelial cell permeability in two different endothelial cell lines, HUVEC and HPMEC.
Fig. S4. Viremia after lethal DENV challenge is reduced by immunization with DENV2 NS1.
Fig. S5. Immunization with DENV NS1 and DENV infection induces serotype cross-reactive anti-NS1 antibodies.REFERENCES AND NOTES
Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control (World Health Organization, Geneva, ed. 2, 1997), pp. 12–23.
Despite the wide selection of vendor-specific information technology security certifications, identifying which...
ones best suit your educational or career needs is fairly straightforward.
This guide to vendor-specific IT security certifications includes an alphabetized table of security certification programs from various vendors, a brief description of each certification and advice for further details.Introduction: Choosing vendor-specific information technology security certifications
The process of choosing the right vendor-specific information technology security certifications is much simpler than choosing vendor-neutral ones. In the vendor-neutral landscape, you must evaluate the pros and cons of various programs to select the best option. On the vendor-specific side, it's only necessary to follow these three steps:
In an environment where qualified IT security professionals can choose from numerous job openings, the benefits of individual training and certifications can be hard to appraise.
Many employers pay certification costs to develop and retain their employees, as well as to boost the organization's in-house expertise. Most see this as a win-win for employers and employees alike, though employers often require full or partial reimbursement for the related costs incurred if employees leave their jobs sooner than some specified payback period after certification.
There have been quite a few changes since the last survey update in 2015. The Basic category saw a substantial jump in the number of available IT security certifications due to the addition of several Brainbench certifications, in addition to the Cisco Certified Network Associate (CCNA) Cyber Ops certification, the Fortinet Network Security Expert Program and new IBM certifications.
Certifications from AccessData, Check Point, IBM and Oracle were added to the Intermediate category, increasing the total number of certifications in that category, as well. However, the number of certifications in the Advanced category decreased, due to several IBM certifications being retired.Basic information technology security certifications
Brainbench basic security certificationsBrainbench offers several basic-level information technology security certifications, each requiring the candidate to pass one exam. Brainbench security-related certifications include:
Source: Brainbench Information Security Administrator certifications
CCNA Cyber OpsPrerequisites: None required; training is recommended.
This associate-level certification prepares cybersecurity professionals for work as cybersecurity analysts responding to security incidents as part of a security operations center team in a large organization.
The CCNA Cyber Ops certification requires candidates to pass two written exams.
Source: Cisco Systems CCNA Cyber Ops
CCNA SecurityPrerequisites: A valid Cisco CCNA Routing and Switching, Cisco Certified Entry Networking Technician or Cisco Certified Internetwork Expert (CCIE) certification.
This credential validates that associate-level professionals are able to install, troubleshoot and monitor Cisco-routed and switched network devices for the purpose of protecting both the devices and networked data.
A person with a CCNA Security certification can be expected to understand core security concepts, endpoint security, web and email content security, the management of secure access, and more. He should also be able to demonstrate skills for building a security infrastructure, identifying threats and vulnerabilities to networks, and mitigating security threats. CCNA credential holders also possess the technical skills and expertise necessary to manage protection mechanisms such as firewalls and intrusion prevention systems, network access, endpoint security solutions, and web and email security.
The successful completion of one exam is required to obtain this credential.
Source: Cisco Systems CCNA Security
Check Point Certified Security Administrator (CCSA) R80Prerequisites: Basic knowledge of networking; CCSA training and six months to one year of experience with Check Point products are recommended.
Check Point's foundation-level credential prepares individuals to install, configure and manage Check Point security system products and technologies, such as security gateways, firewalls and virtual private networks (VPNs). Credential holders also possess the skills necessary to secure network and internet communications, upgrade products, troubleshoot network connections, configure security policies, protect email and message content, defend networks from intrusions and other threats, analyze attacks, manage user access in a corporate LAN environment, and configure tunnels for remote access to corporate resources.
Candidates must pass a single exam to obtain this credential.
Source: Check Point CCSA Certification
IBM Certified Associate -- Endpoint Manager V9.0Prerequisites: IBM suggests that candidates be highly familiar with the IBM Endpoint Manager V9.0 console. They should have experience taking actions; activating analyses; and using Fixlets, tasks and baselines in the environment. They should also understand patching, component services, client log files and troubleshooting within IBM Endpoint Manager.
This credential recognizes professionals who use IBM Endpoint Manager V9.0 daily. Candidates for this certification should know the key concepts of Endpoint Manager, be able to describe the system's components and be able to use the console to perform routine tasks.
Successful completion of one exam is required.
Editor's note: IBM is retiring this certification as of May 31, 2017; there will be a follow-on test available as of April 2017 for IBM BigFix Compliance V9.5 Fundamental Administration, Test C2150-627.
Source: IBM Certified Associate -- Endpoint Manager V9.0
IBM Certified Associate -- Security Trusteer Fraud ProtectionPrerequisites: IBM recommends that candidates have experience with network data communications, network security, and the Windows and Mac operating systems.
This credential pertains mainly to sales engineers who support the Trusteer Fraud product portfolio for web fraud management, and who can implement a Trusteer Fraud solution. Candidates must understand Trusteer product functionality, know how to deploy the product, and be able to troubleshoot the product and analyze the results.
To obtain this certification, candidates must pass one exam.
Source: IBM Certified Associate -- Security Trusteer Fraud Protection
McAfee Product SpecialistPrerequisites: None required; completion of an associated training course is highly recommended.
McAfee information technology security certification holders possess the knowledge and technical skills necessary to install, configure, manage and troubleshoot specific McAfee products, or, in some cases, a suite of products.
Candidates should possess one to three years of direct experience with one of the specific product areas.
The current products targeted by this credential include:
All credentials require passing one exam.
Source: McAfee Certification Program
Microsoft Technology Associate (MTA)Prerequisites: None; training recommended.
This credential started as an academic-only credential for students, but Microsoft made it available to the general public in 2012.
There are 10 different MTA credentials across three tracks (IT Infrastructure with five certs, Database with one and Development with four). The IT Infrastructure track includes a Security Fundamentals credential, and some of the other credentials include security components or topic areas.
To earn each MTA certification, candidates must pass the corresponding exam.
Source: Microsoft MTA Certifications
Fortinet Network Security Expert (NSE)Prerequisites: Vary by credential.
The Fortinet NSE program has eight levels, each of which corresponds to a separate network security credential within the program. The credentials are:
NSE 1 is open to anyone, but is not required. The NSE 2 and NSE 3 information technology security certifications are available only to Fortinet employees and partners. Candidates for NSE 4 through NSE 8 should take the exams through Pearson VUE.
Source: Fortinet NSE
Symantec Certified Specialist (SCS)This security certification program focuses on data protection, high availability and security skills involving Symantec products.
To become an SCS, candidates must select an area of focus and pass an exam. All the exams cover core elements, such as installation, configuration, product administration, day-to-day operation and troubleshooting for the selected focus area.
As of this writing, the following exams are available:
Source: Symantec CertificationIntermediate information technology security certifications
AccessData Certified Examiner (ACE)Prerequisites: None required; the AccessData BootCamp and Advanced Forensic Toolkit (FTK) courses are recommended.
This credential recognizes a professional's proficiency using AccessData's FTK, FTK Imager, Registry Viewer and Password Recovery Toolkit. However, candidates for the certification must also have moderate digital forensic knowledge and be able to interpret results gathered from AccessData tools.
To obtain this certification, candidates must pass one online exam (which is free). Although a boot camp and advanced courses are available for a fee, AccessData provides a set of free exam preparation videos to help candidates who prefer to self-study.
The certification is valid for two years, after which credential holders must take the current exam to maintain their certification.
Source: Syntricate ACE Training
Cisco Certified Network Professional (CCNP) Security Prerequisites: CCNA Security or any CCIE certification.
This Cisco credential recognizes professionals who are responsible for router, switch, networking device and appliance security. Candidates must also know how to select, deploy, support and troubleshoot firewalls, VPNs and intrusion detection system/intrusion prevention system products in a networking environment.
Successful completion of four exams is required.
Source: Cisco Systems CCNP Security
Check Point Certified Security Expert (CCSE)Prerequisite: CCSA certification R70 or later.
This is an intermediate-level credential for security professionals seeking to demonstrate skills at maximizing the performance of security networks.
A CCSE demonstrates a knowledge of strategies and advanced troubleshooting for Check Point's GAiA operating system, including installing and managing VPN implementations, advanced user management and firewall concepts, policies, and backing up and migrating security gateway and management servers, among other tasks. The CCSE focuses on Check Point's VPN, Security Gateway and Management Server systems.
To acquire this credential, candidates must pass one exam.
Source: Check Point CCSE program
Cisco Cybersecurity SpecialistPrerequisites: None required; CCNA Security certification and an understanding of TCP/IP are strongly recommended.
This Cisco credential targets IT security professionals who possess in-depth technical skills and knowledge in the field of threat detection and mitigation. The certification focuses on areas such as event monitoring, event analysis (traffic, alarm, security events) and incident response.
One exam is required.
Source: Cisco Systems Cybersecurity Specialist
Certified SonicWall Security Administrator (CSSA)Prerequisites: None required; training is recommended.
The CSSA exam covers basic administration of SonicWall appliances and the network and system security behind such appliances.
Classroom training is available, but not required to earn the CSSA. Candidates must pass one exam to become certified.
Source: SonicWall Certification programs
EnCase Certified Examiner (EnCE)Prerequisites: Candidates must attend 64 hours of authorized training or have 12 months of computer forensic work experience. Completion of a formal application process is also required.
Aimed at both private- and public-sector computer forensic specialists, this certification permits individuals to become certified in the use of Guidance Software's EnCase computer forensics tools and software.
Individuals can gain this certification by passing a two-phase exam: a computer-based component and a practical component.
Source: Guidance Software EnCE
EnCase Certified eDiscovery Practitioner (EnCEP)Prerequisites: Candidates must attend one of two authorized training courses and have three months of experience in eDiscovery collection, processing and project management. A formal application process is also required.
Aimed at both private- and public-sector computer forensic specialists, this certification permits individuals to become certified in the use of Guidance Software's EnCase eDiscovery software, and it recognizes their proficiency in eDiscovery planning, project management and best practices, from legal hold to file creation.
EnCEP-certified professionals possess the technical skills necessary to manage e-discovery, including the search, collection, preservation and processing of electronically stored information in accordance with the Federal Rules of Civil Procedure.
Individuals can gain this certification by passing a two-phase exam: a computer-based component and a scenario component.
Source: Guidance Software EnCEP Certification Program
IBM Certified Administrator -- Security Guardium V10.0Prerequisites: IBM recommends basic knowledge of operating systems and databases, hardware or virtual machines, networking and protocols, auditing and compliance, and information security guidelines.
IBM Security Guardium is a suite of protection and monitoring tools designed to protect databases and big data sets. The IBM Certified Administrator -- Security Guardium credential is aimed at administrators who plan, install, configure and manage Guardium implementations. This may include monitoring the environment, including data; defining policy rules; and generating reports.
Successful completion of one exam is required.
Source: IBM Security Guardium Certification
IBM Certified Administrator -- Security QRadar Risk Manager V7.2.6Prerequisites: IBM recommends a working knowledge of IBM Security QRadar SIEM Administration and IBM Security QRadar Risk Manager, as well as general knowledge of networking, risk management, system administration and network topology.
QRadar Risk Manager automates the risk management process in enterprises by monitoring network device configurations and compliance. The IBM Certified Administrator -- Security QRadar Risk Manager V7.2.6 credential certifies administrators who use QRadar to manage security risks in their organization. Certification candidates must know how to review device configurations, manage devices, monitor policies, schedule tasks and generate reports.
Successful completion of one exam is required.
Source: IBM Security QRadar Risk Manager Certification
IBM Certified Analyst -- Security SiteProtector System V3.1.1Prerequisites: IBM recommends a basic knowledge of the IBM Security Network Intrusion Prevention System (GX) V4.6.2, IBM Security Network Protection (XGS) V5.3.1, Microsoft SQL Server, Windows Server operating system administration and network security.
The Security SiteProtector System enables organizations to centrally manage their network, server and endpoint security agents and appliances. The IBM Certified Analyst -- Security SiteProtector System V3.1.1 credential is designed to certify security analysts who use the SiteProtector System to monitor and manage events, monitor system health, optimize SiteProtector and generate reports.
To obtain this certification, candidates must pass one exam.
Source: IBM Security SiteProtector Certification
Oracle Certified Expert, Oracle Solaris 10 Certified Security AdministratorPrerequisite: Oracle Certified Professional, Oracle Solaris 10 System Administrator.
This credential aims to certify experienced Solaris 10 administrators with security interest and experience. It's a midrange credential that focuses on general security principles and features, installing systems securely, application and network security, principle of least privilege, cryptographic features, auditing, and zone security.
A single exam -- geared toward the Solaris 10 operating system or the OpenSolaris environment -- is required to obtain this credential.
Source: Oracle Solaris Certification
Oracle Mobile SecurityPrerequisites: Oracle recommends that candidates understand enterprise mobility, mobile application management and mobile device management; have two years of experience implementing Oracle Access Management Suite Plus 11g; and have experience in at least one other Oracle product family.
This credential recognizes professionals who create configuration designs and implement the Oracle Mobile Security Suite. Candidates must have a working knowledge of Oracle Mobile Security Suite Access Server, Oracle Mobile Security Suite Administrative Console, Oracle Mobile Security Suite Notification Server, Oracle Mobile Security Suite Containerization and Oracle Mobile Security Suite Provisioning and Policies. They must also know how to deploy the Oracle Mobile Security Suite.
Although the certification is designed for Oracle PartnerNetwork members, it is available to any candidate. Successful completion of one exam is required.
Source: Oracle Mobile Security Certification
RSA Archer Certified Administrator (CA)Prerequisites: None required; Dell EMC highly recommends RSA training and two years of product experience as preparation for the RSA certification exams.
Dell EMC offers this certification, which is designed for security professionals who manage, administer, maintain and troubleshoot the RSA Archer Governance, Risk and Compliance (GRC) platform.
Candidates must pass one exam, which focuses on integration and configuration management, security administration, and the data presentation and communication features of the RSA Archer GRC product.
Source: Dell EMC RSA Archer Certification
RSA SecurID Certified Administrator (RSA Authentication Manager 8.0)Prerequisites: None required; Dell EMC highly recommends RSA training and two years of product experience as preparation for the RSA certification exams.
Dell EMC offers this certification, which is designed for security professionals who manage, maintain and administer enterprise security systems based on RSA SecurID system products and RSA Authentication Manager 8.0.
RSA SecurID CAs can operate and maintain RSA SecurID components within the context of their operational systems and environments; troubleshoot security and implementation problems; and work with updates, patches and fixes. They can also perform administrative functions and populate and manage users, set up and use software authenticators, and understand the configuration required for RSA Authentication Manager 8.0 system operations.
Source: Dell EMC RSA Authentication Manager Certification
RSA Security Analytics CAPrerequisites: None required; Dell EMC highly recommends RSA training and two years of product experience as preparation for the RSA certification exams.
This Dell EMC certification is aimed at security professionals who configure, manage, administer and troubleshoot the RSA Security Analytics product. Knowledge of the product's features, as well the ability to use the product to identify security concerns, are required.
Candidates must pass one exam, which focuses on RSA Security Analytics functions and capabilities, configuration, management, monitoring and troubleshooting.
Source: Dell EMC RSA Security AnalyticsAdvanced information technology security certifications
CCIE SecurityPrerequisites: None required; three to five years of professional working experience recommended.
Arguably one of the most coveted certifications around, the CCIE is in a league of its own. Having been around since 2002, the CCIE Security track is unrivaled for those interested in dealing with information security topics, tools and technologies in networks built using or around Cisco products and platforms.
The CCIE certifies that candidates possess expert technical skills and knowledge of security and VPN products; an understanding of Windows, Unix, Linux, network protocols and domain name systems; an understanding of identity management; an in-depth understanding of Layer 2 and 3 network infrastructures; and the ability to configure end-to-end secure networks, as well as to perform troubleshooting and threat mitigation.
To achieve this certification, candidates must pass both a written and lab exam. The lab exam must be passed within 18 months of the successful completion of the written exam.
Source: Cisco Systems CCIE Security Certification
Check Point Certified Managed Security Expert (CCMSE)Prerequisites: CCSE certification R75 or later and 6 months to 1 year of experience with Check Point products.
This advanced-level credential is aimed at those seeking to learn how to install, configure and troubleshoot Check Point's Multi-Domain Security Management with Virtual System Extension.
Professionals are expected to know how to migrate physical firewalls to a virtualized environment, install and manage an MDM environment, configure high availability, implement global policies and perform troubleshooting.
Source: Check Point CCMSE
Check Point Certified Security Master (CCSM)Prerequisites: CCSE R70 or later and experience with Windows Server, Unix, TCP/IP, and networking and internet technologies.
The CCSM is the most advanced Check Point certification available. This credential is aimed at security professionals who implement, manage and troubleshoot Check Point security products. Candidates are expected to be experts in perimeter, internal, web and endpoint security systems.
To acquire this credential, candidates must pass a written exam.
Source: Check Point CCSM Certification
Certified SonicWall Security Professional (CCSP)Prerequisites: Attendance at an advanced administration training course.
Those who achieve this certification have attained a high level of mastery of SonicWall products. In addition, credential holders should be able to deploy, optimize and troubleshoot all the associated product features.
Earning a CSSP requires taking an advanced administration course that focuses on either network security or secure mobile access, and passing the associated certification exam.
Source: SonicWall CSSP certification
IBM Certified Administrator -- Tivoli Monitoring V6.3Prerequisites: Security-related requirements include basic knowledge of SSL, data encryption and system user accounts.
Those who attain this certification are expected to be capable of planning, installing, configuring, upgrading and customizing workspaces, policies and more. In addition, credential holders should be able to troubleshoot, administer and maintain an IBM Tivoli Monitoring V6.3 environment.
Candidates must successfully pass one exam.
Source: IBM Tivoli Certified Administrator
Master Certified SonicWall Security Administrator (CSSA)The Master CSSA is an intermediate between the base-level CSSA credential (itself an intermediate certification) and the CSSP.
To qualify for Master CSSA, candidates must pass three (or more) CSSA exams, and then email firstname.lastname@example.org to request the designation. There are no other charges or requirements involved.
Source: SonicWall Master CSSAConclusion
Remember, when it comes to selecting vendor-specific information technology security certifications, your organization's existing or planned security product purchases should dictate your options. If your security infrastructure includes products from vendors not mentioned here, be sure to check with them to determine if training or certifications on such products are available.
About the author:Ed Tittel is a 30-plus year IT veteran who's worked as a developer, networking consultant, technical trainer, writer and expert witness. Perhaps best known for creating the Exam Cram series, Ed has contributed to more than 100 books on many computing topics, including titles on information security, Windows OSes and HTML. Ed also blogs regularly for TechTarget (Windows Enterprise Desktop), Tom's IT Pro and GoCertify.
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Altiris [3 Certification Exam(s) ]
Amazon [2 Certification Exam(s) ]
American-College [2 Certification Exam(s) ]
Android [4 Certification Exam(s) ]
APA [1 Certification Exam(s) ]
APC [2 Certification Exam(s) ]
APICS [2 Certification Exam(s) ]
Apple [69 Certification Exam(s) ]
AppSense [1 Certification Exam(s) ]
APTUSC [1 Certification Exam(s) ]
Arizona-Education [1 Certification Exam(s) ]
ARM [1 Certification Exam(s) ]
Aruba [6 Certification Exam(s) ]
ASIS [2 Certification Exam(s) ]
ASQ [3 Certification Exam(s) ]
ASTQB [8 Certification Exam(s) ]
Autodesk [2 Certification Exam(s) ]
Avaya [96 Certification Exam(s) ]
AXELOS [1 Certification Exam(s) ]
Axis [1 Certification Exam(s) ]
Banking [1 Certification Exam(s) ]
BEA [5 Certification Exam(s) ]
BICSI [2 Certification Exam(s) ]
BlackBerry [17 Certification Exam(s) ]
BlueCoat [2 Certification Exam(s) ]
Brocade [4 Certification Exam(s) ]
Business-Objects [11 Certification Exam(s) ]
Business-Tests [4 Certification Exam(s) ]
CA-Technologies [21 Certification Exam(s) ]
Certification-Board [10 Certification Exam(s) ]
Certiport [3 Certification Exam(s) ]
CheckPoint [41 Certification Exam(s) ]
CIDQ [1 Certification Exam(s) ]
CIPS [4 Certification Exam(s) ]
Cisco [318 Certification Exam(s) ]
Citrix [48 Certification Exam(s) ]
CIW [18 Certification Exam(s) ]
Cloudera [10 Certification Exam(s) ]
Cognos [19 Certification Exam(s) ]
College-Board [2 Certification Exam(s) ]
CompTIA [76 Certification Exam(s) ]
ComputerAssociates [6 Certification Exam(s) ]
Consultant [2 Certification Exam(s) ]
Counselor [4 Certification Exam(s) ]
CPP-Institue [2 Certification Exam(s) ]
CPP-Institute [1 Certification Exam(s) ]
CSP [1 Certification Exam(s) ]
CWNA [1 Certification Exam(s) ]
CWNP [13 Certification Exam(s) ]
Dassault [2 Certification Exam(s) ]
DELL [9 Certification Exam(s) ]
DMI [1 Certification Exam(s) ]
DRI [1 Certification Exam(s) ]
ECCouncil [21 Certification Exam(s) ]
ECDL [1 Certification Exam(s) ]
EMC [129 Certification Exam(s) ]
Enterasys [13 Certification Exam(s) ]
Ericsson [5 Certification Exam(s) ]
ESPA [1 Certification Exam(s) ]
Esri [2 Certification Exam(s) ]
ExamExpress [15 Certification Exam(s) ]
Exin [40 Certification Exam(s) ]
ExtremeNetworks [3 Certification Exam(s) ]
F5-Networks [20 Certification Exam(s) ]
FCTC [2 Certification Exam(s) ]
Filemaker [9 Certification Exam(s) ]
Financial [36 Certification Exam(s) ]
Food [4 Certification Exam(s) ]
Fortinet [13 Certification Exam(s) ]
Foundry [6 Certification Exam(s) ]
FSMTB [1 Certification Exam(s) ]
Fujitsu [2 Certification Exam(s) ]
GAQM [9 Certification Exam(s) ]
Genesys [4 Certification Exam(s) ]
GIAC [15 Certification Exam(s) ]
Google [4 Certification Exam(s) ]
GuidanceSoftware [2 Certification Exam(s) ]
H3C [1 Certification Exam(s) ]
HDI [9 Certification Exam(s) ]
Healthcare [3 Certification Exam(s) ]
HIPAA [2 Certification Exam(s) ]
Hitachi [30 Certification Exam(s) ]
Hortonworks [4 Certification Exam(s) ]
Hospitality [2 Certification Exam(s) ]
HP [750 Certification Exam(s) ]
HR [4 Certification Exam(s) ]
HRCI [1 Certification Exam(s) ]
Huawei [21 Certification Exam(s) ]
Hyperion [10 Certification Exam(s) ]
IAAP [1 Certification Exam(s) ]
IAHCSMM [1 Certification Exam(s) ]
IBM [1532 Certification Exam(s) ]
IBQH [1 Certification Exam(s) ]
ICAI [1 Certification Exam(s) ]
ICDL [6 Certification Exam(s) ]
IEEE [1 Certification Exam(s) ]
IELTS [1 Certification Exam(s) ]
IFPUG [1 Certification Exam(s) ]
IIA [3 Certification Exam(s) ]
IIBA [2 Certification Exam(s) ]
IISFA [1 Certification Exam(s) ]
Intel [2 Certification Exam(s) ]
IQN [1 Certification Exam(s) ]
IRS [1 Certification Exam(s) ]
ISA [1 Certification Exam(s) ]
ISACA [4 Certification Exam(s) ]
ISC2 [6 Certification Exam(s) ]
ISEB [24 Certification Exam(s) ]
Isilon [4 Certification Exam(s) ]
ISM [6 Certification Exam(s) ]
iSQI [7 Certification Exam(s) ]
ITEC [1 Certification Exam(s) ]
Juniper [64 Certification Exam(s) ]
LEED [1 Certification Exam(s) ]
Legato [5 Certification Exam(s) ]
Liferay [1 Certification Exam(s) ]
Logical-Operations [1 Certification Exam(s) ]
Lotus [66 Certification Exam(s) ]
LPI [24 Certification Exam(s) ]
LSI [3 Certification Exam(s) ]
Magento [3 Certification Exam(s) ]
Maintenance [2 Certification Exam(s) ]
McAfee [8 Certification Exam(s) ]
McData [3 Certification Exam(s) ]
Medical [69 Certification Exam(s) ]
Microsoft [374 Certification Exam(s) ]
Mile2 [3 Certification Exam(s) ]
Military [1 Certification Exam(s) ]
Misc [1 Certification Exam(s) ]
Motorola [7 Certification Exam(s) ]
mySQL [4 Certification Exam(s) ]
NBSTSA [1 Certification Exam(s) ]
NCEES [2 Certification Exam(s) ]
NCIDQ [1 Certification Exam(s) ]
NCLEX [2 Certification Exam(s) ]
Network-General [12 Certification Exam(s) ]
NetworkAppliance [39 Certification Exam(s) ]
NI [1 Certification Exam(s) ]
NIELIT [1 Certification Exam(s) ]
Nokia [6 Certification Exam(s) ]
Nortel [130 Certification Exam(s) ]
Novell [37 Certification Exam(s) ]
OMG [10 Certification Exam(s) ]
Oracle [279 Certification Exam(s) ]
P&C [2 Certification Exam(s) ]
Palo-Alto [4 Certification Exam(s) ]
PARCC [1 Certification Exam(s) ]
PayPal [1 Certification Exam(s) ]
Pegasystems [12 Certification Exam(s) ]
PEOPLECERT [4 Certification Exam(s) ]
PMI [15 Certification Exam(s) ]
Polycom [2 Certification Exam(s) ]
PostgreSQL-CE [1 Certification Exam(s) ]
Prince2 [6 Certification Exam(s) ]
PRMIA [1 Certification Exam(s) ]
PsychCorp [1 Certification Exam(s) ]
PTCB [2 Certification Exam(s) ]
QAI [1 Certification Exam(s) ]
QlikView [1 Certification Exam(s) ]
Quality-Assurance [7 Certification Exam(s) ]
RACC [1 Certification Exam(s) ]
Real-Estate [1 Certification Exam(s) ]
RedHat [8 Certification Exam(s) ]
RES [5 Certification Exam(s) ]
Riverbed [8 Certification Exam(s) ]
RSA [15 Certification Exam(s) ]
Sair [8 Certification Exam(s) ]
Salesforce [5 Certification Exam(s) ]
SANS [1 Certification Exam(s) ]
SAP [98 Certification Exam(s) ]
SASInstitute [15 Certification Exam(s) ]
SAT [1 Certification Exam(s) ]
SCO [10 Certification Exam(s) ]
SCP [6 Certification Exam(s) ]
SDI [3 Certification Exam(s) ]
See-Beyond [1 Certification Exam(s) ]
Siemens [1 Certification Exam(s) ]
Snia [7 Certification Exam(s) ]
SOA [15 Certification Exam(s) ]
Social-Work-Board [4 Certification Exam(s) ]
SpringSource [1 Certification Exam(s) ]
SUN [63 Certification Exam(s) ]
SUSE [1 Certification Exam(s) ]
Sybase [17 Certification Exam(s) ]
Symantec [134 Certification Exam(s) ]
Teacher-Certification [4 Certification Exam(s) ]
The-Open-Group [8 Certification Exam(s) ]
TIA [3 Certification Exam(s) ]
Tibco [18 Certification Exam(s) ]
Trainers [3 Certification Exam(s) ]
Trend [1 Certification Exam(s) ]
TruSecure [1 Certification Exam(s) ]
USMLE [1 Certification Exam(s) ]
VCE [6 Certification Exam(s) ]
Veeam [2 Certification Exam(s) ]
Veritas [33 Certification Exam(s) ]
Vmware [58 Certification Exam(s) ]
Wonderlic [2 Certification Exam(s) ]
Worldatwork [2 Certification Exam(s) ]
XML-Master [3 Certification Exam(s) ]
Zend [6 Certification Exam(s) ]
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