West Nile Virus Inhibits the Signal Transduction Pathway of Alpha Interferon

Guo, Ju‐Tao; Hayashi, J.; Seeger, Christoph

doi:10.1128/jvi.79.3.1343-1350.2005

Cited by 201 publications

(181 citation statements)

References 41 publications

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“…The anamnestic response among YF-immune subjects could have great implications for the development of an immunization strategy for a tetravalent vaccine by avoiding the potential interference problem that presenting a single YF-DEN chimeric virus poses to the host. In this instance, the induction of interferon occurs in concert with virus replication and is modulated effectively by the YF nonstructural proteins 18,19 to allow sufficient replication required for immunization. Since the initial immunizing agent (YF) is incapable of sensitizing the subject to DHF, there will be no danger that the first (priming) inoculation would leave the subject vulnerable to this disease if the second injection was delayed or not administered.…”

Section: Discussionmentioning

confidence: 99%

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Guirakhoo

Kitchener²,

Morrison³

et al. 2006

Human Vaccines

187

136

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A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX ® ). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX ® by the subcutaneous route (SC). To determine the effect of YF preimmunity on the ChimeriVax TM -DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX ® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log 10 PFU of ChimeriVax TM -DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX ® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX ® . In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that (1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX ® , and (2) preimmunity to YF virus does not interfere with ChimeriVax TM -DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine.

show abstract

Section: Discussionmentioning

confidence: 99%

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Guirakhoo

Kitchener²,

Morrison³

et al. 2006

Human Vaccines

187

136

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“…There are many circumstances in which the host's immunological environment is altered. These may include various forms of inherent immunodeficiencies; altered immune status due to aging [7][8][9][10][11][12][13][14], as well as results of prior and/or concurrent infections [15][16][17][18][19][20][21][22]. Previously, we have shown that a number of adjuvant formulations differ in their ability to potentiate the immunogenicity of a malaria vaccine under the altered immunological environment created by Interferon-γ and Interleukin-4 knockouts [23].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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The efficacy of vaccine adjuvants can be influenced by the immunological environment of the host, depending on the mechanism(s) by which they exert their immunopotentiating activities. Interleukin-6 is a pleiotropic cytokine that has a broad range of biological activities on immune and non-immune cells. We investigated the role of IL-6 on the ability of nine adjuvant formulations to induce antibody responses to the P. falciparum MSP1-19 malaria vaccine, using IL-6 -/-(KO) mice. Results showed that some adjuvants, ie. MPL-SE, CFA/IFA, ISA720/QS21/MPL, depended on IL-6 for their efficacy, while others exhibited increased potency in its absence. The efficacy of adjuvants in the IL-6 KO environment cannot be solely attributed to their ability to stimulate antigen-specific cellular responses, suggesting that other biological activities of IL-6 are also important. The results further suggest that two adjuvants utilized dissimilar pathways to potentiate the same type of immune response.

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“…Importantly, virulence of the normally nonpathogenic WNV-MAD78 virus was unmasked upon infection of mice lacking a functional α/β IFN receptor. All WNV strains thus far shown by other groups to antagonize α/β IFN receptor signaling were derived from pathogenic isolates of the virus [49,50,53]. These studies demonstrate that the antiviral actions of α/β IFNs are essential for immunity and protection against WNV infection, and define viral suppression of JAK-Stat signaling through the α/β IFN receptor as a major determinant of WNV pathogenesis.…”

Section: Wnv Disruption Of α/β Ifn Receptor Signaling Is a Pathogenesmentioning

confidence: 72%

“…Several groups have recently reported that WNV is capable of inhibiting activation of JAK-STAT signaling components [48][49][50][51]. However, the exact mechanism of this inhibition is not clear, as it has been proposed that the NS2A, NS2B3, NS4A and NS4B viral proteins each have inhibitory activity against IFN signaling.…”

Section: Wnv Disruption Of α/β Ifn Receptor Signaling Is a Pathogenesmentioning

confidence: 99%

Innate immune evasion by hepatitis C virus and West Nile virus

Keller

Johnson

Erickson

et al. 2007

Cytokine & Growth Factor Reviews

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Antiviral immunity in mammals involves several levels of surveillance and effector actions by host factors to detect viral pathogens, trigger α/β interferon production, and to mediate innate defenses within infected cells. Our studies have focused on understanding how these processes are regulated during infection by hepatitis C virus (HCV) and West Nile virus (WNV). Both viruses are members of the Flaviviridae and are human pathogens but they each mediate a very different disease and course of infection. Our results demonstrate common and unique innate immune interactions of each virus that govern antiviral immunity, and demonstrate the central role of α/β interferon immune defenses in controlling the outcome of infection.

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West Nile Virus Inhibits the Signal Transduction Pathway of Alpha Interferon

Cited by 201 publications

References 41 publications

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Innate immune evasion by hepatitis C virus and West Nile virus

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