Isolation and Characterization of Human Monoclonal Antibodies from Individuals Infected with West Nile Virus

Throsby, Mark; Geuijen, Cecile; Goudsmit, Jaap; Bakker, Arjen Q.; Korimbocus, Jehanara; Kramer, R. Arjen; Horst, Marieke Clijsters-van der; Jong, Maureen de; Jongeneelen, Mandy; Thijsse, Sandra; Smit, Renate; Visser, Therèse; Bijl, Nora; Marissen, Wilfred Ε.; Loeb, Mark; Kelvin, David J.; Preiser, Wolfgang; Meulen, Jan ter; Kruif, John de

doi:10.1128/jvi.00551-06

Cited by 155 publications

(186 citation statements)

References 38 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: 90%

“…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: 90%

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

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“…CR4354 was selected from a single-chain variable fragment (scFv) phage display library constructed from peripheral blood lymphocytes isolated from human patients who survived neuroinvasive WNV disease (33). The reformatting of CR4354 scFv phage into full-length IgG1 was done as described previously (34).…”

Section: Methodsmentioning

confidence: 99%

Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354

Kaufmann

Vogt²,

Goudsmit³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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124

121

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Many flaviviruses are significant human pathogens, with the humoral immune response playing an essential role in restricting infection and disease. CR4354, a human monoclonal antibody isolated from a patient, neutralizes West Nile virus (WNV) infection at a postattachment stage in the viral life-cycle. Here, we determined the structure of WNV complexed with Fab fragments of CR4354 using cryoelectron microscopy. The outer glycoprotein shell of a mature WNV particle is formed by 30 rafts of three homodimers of the viral surface protein E. CR4354 binds to a discontinuous epitope formed by protein segments from two neighboring E molecules, but does not cause any detectable structural disturbance on the viral surface. The epitope occurs at two independent positions within an icosahedral asymmetric unit, resulting in 120 binding sites on the viral surface. The cross-linking of the six E monomers within one raft by four CR4354 Fab fragments suggests that the antibody neutralizes WNV by blocking the pH-induced rearrangement of the E protein required for virus fusion with the endosomal membrane.antibody | cryoelectron microscopy | flavivirus W est Nile virus (WNV) is a human pathogen that causes a febrile illness, which can progress to encephalitis, paralysis, and death. The virus is endemic in parts of Africa, Asia, and Europe, and in the past decade has spread throughout North America and into Central and South America (1). WNV is closely related to other arthropod-transmitted, medically relevant flaviviruses, such as dengue, yellow fever, Japanese encephalitis, and tick-borne encephalitis viruses. These lipid-enveloped viruses enter host cells by receptor-mediated endocytosis. The singlestranded, positive-sense RNA genome is released into the cytoplasm after low pH induces the fusion of the viral lipid envelope with the endosomal membrane.Mature WNV virions are roughly spherical with a diameter of about 500 Å. The outer viral surface is composed of an icosahedral scaffold of 180 closely packed copies of the membrane-anchored envelope (E) glycoprotein. Sets of three, nearly parallel E homodimers are associated into rafts that form a herringbone pattern on the surface of mature virions. The ectodomain of E has three structural domains, DI, DII, and DIII (2-5), with domain DI positioned structurally between DII and DIII. DII contains a fusion loop at its distal end that is indispensable for virus-cell membrane fusion. The Ig-like C-terminal domain DIII undergoes a major, pH-triggered positional rearrangement essential for fusion, and may also be involved in receptor binding (2, 6-12). During cell entry of flaviviruses, low endosomal pH triggers a proposed E protein rearrangement cascade, including the dissociation of E dimers and the outward rotation of DII during the repositioning of E monomers into fusion-active trimers (6, 9, 13).The humoral immune response is essential for protection against flavivirus infection and disease (14,15). The E glycoprotein is the principal antigen that elicits neutralizing antibodies agai...

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West Nile Virus: A Narrative from Bioinformatics and Mathematical Modeling Studies

Murty

Banerjee

2014

Wiley Series in Probability and Statistics

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Isolation and Characterization of Human Monoclonal Antibodies from Individuals Infected with West Nile Virus

Cited by 155 publications

References 38 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

Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354

West Nile Virus: A Narrative from Bioinformatics and Mathematical Modeling Studies

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