Protective and Therapeutic Capacity of Human Single-Chain Fv-Fc Fusion Proteins against West Nile Virus

Gould, L. Hannah; Sui, Jianhua; Foellmer, Harald G.; Oliphant, Theodore; Wang, Tian; Ledizet, Michel; Murakami, Akikazu; Noonan, Kimberly; Lambeth, Cassandra; Kar, Kalipada; Anderson, John F.; Silva, Aravinda M. de; Diamond, Michael S.; Koski, Raymond A.; Marasco, Wayne A.; Fikrig, Erol

doi:10.1128/jvi.79.23.14606-14613.2005

Cited by 112 publications

(125 citation statements)

References 36 publications

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“…Previous studies have established that a WNVspecific humoral response prevents CNS dissemination during primary infection [5,40]. Moreover, passive administration of immune serum, WNV specific mouse or human monoclonal antibodies (mAbs), or human immune γglobulin completely protects mice from lethal primary WNV infection [5][6][7][8][9][10][11]40]. Based on these findings, we expected that the induction of high-titer WNV-specific antibodies by candidate vaccines was essential for protection.…”

Section: Humoral Immune Response Induced By Candidate Vaccinesmentioning

confidence: 95%

“…Passive transfer of monoclonal or polyclonal antibodies protect mice and hamsters from lethal subcutaneous or intraperitoneal WNV challenge [5][6][7][8]10,11,15,40,56]. To address the relative potency of the WNV-specific antibody response generated by the vaccines, we passively transferred serum from immunized to younger naïve mice before lethal peripheral challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have established that in vitro neutralization activity of anti-WNV antibodies correlates with in vivo protection [7,8,10,11]. To determine how successful the different vaccine candidates were at generating functionally relevant antibodies, we tested serum for neutralizing assay in a plaque reduction assay.…”

Section: Humoral Immune Response Induced By Candidate Vaccinesmentioning

confidence: 99%

“…The induction of high-titer WNV-specific and neutralizing antibodies after infection has been assumed as a primary mechanism of control during secondary challenge. Indeed, passive transfer of immune serum, monoclonal antibodies or polyclonal antibodies protects rodents from lethal primary WNV infection [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

Shrestha

Chu

et al. 2008

Vaccine

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West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigenspecific CD8 + T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8 + T cells lowered the survival rates. In contrast, in boosted animals, WNVspecific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8 + T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8 + T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.

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Section: Humoral Immune Response Induced By Candidate Vaccinesmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Humoral Immune Response Induced By Candidate Vaccinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

Shrestha

Chu

et al. 2008

Vaccine

Self Cite

View full text Add to dashboard Cite

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“…The dominant neutralizing epitopes have been mapped to one of three domains of the envelope protein, domain III, using monoclonal antibodies for dengue virus [9], as well as JEV [10] and WNV [11]. Additional neutralizing epitopes have recently been identified on domains I and II of the envelope protein as well [12]. Neutralizing antibodies (recognizing domain III epitopes) are generally specific for each virus and do not crossneutralize other viruses (or other serotypes of the same virus if multiple serotypes exist).…”

Section: Introductionmentioning

confidence: 99%

Preparation and immunogenic properties of a recombinant West Nile subunit vaccine

Lieberman

Clements

Ogata

et al. 2007

Vaccine

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While several West Nile vaccines are being developed, none are yet available for humans. In this study aimed at developing a vaccine for humans, West Nile virus (WNV) envelope protein (E) and non-structural protein 1 (NS1) were produced in the Drosophila S2 cell expression system. The Cterminal 20% of the E protein, which contains the membrane anchor portion, was deleted, thus allowing for efficient secretion of the truncated protein (80E) into the cell culture medium. The proteins were purified by immunoaffinity chromatography (IAC) using monoclonal antibodies that were flavivirus envelope protein group specific (for the 80E) or flavivirus NS1 group specific (for NS1). The purified proteins were produced in high yield and used in conjunction with adjuvant formulations to vaccinate mice. The mice were tested for both humoral and cellular immune responses by a plaque reduction neutralization test and ELISA, and by lymphocyte proliferation and cytokine production assays, respectively. The results revealed that the 80E and the NS1 proteins induced both high-titered ELISA and neutralizing antibodies in mice. Splenocytes from immunized mice, cultured in vitro with the vaccine antigens as stimulants, showed excellent proliferation and production of cytokines . The level of antigen-stimulated lymphocyte proliferation and cytokine production was comparable to the level obtained from mitogen (phytohemagglutinin or pokeweed) stimulation, indicating a robust cellular response as well. These findings are encouraging and warrant further in vivo studies to determine the protective efficacy of the WNV vaccine candidate.

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Pathogenesis of West Nile Virus in Humans

Vandergaast

Hussmann

Fredericksen

2015

Human Emerging and Re‐emerging Infections

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Protective and Therapeutic Capacity of Human Single-Chain Fv-Fc Fusion Proteins against West Nile Virus

Cited by 112 publications

References 36 publications

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

Preparation and immunogenic properties of a recombinant West Nile subunit vaccine

Pathogenesis of West Nile Virus in Humans

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