High Throughput Quantitative Colorimetric Microneutralization Assay for the Confirmation and Differentiation of West Nile Virus and St. Louis Encephalitis Virus

Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity—including fever, viremia, and viral loads in spinal cord and testes—and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.

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“…S10). These results resemble titers of humans with waning immune responses after natural exposure to DENV (35, 36). …”

mentioning

confidence: 54%

Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

Bardina

Bunduc

Tripathi

et al. 2017

Science

466

480

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“…This trend most likely relates to changes in age structure, with progressively more parous female mosquitoes tested as overall vector population numbers decline. Sentinel chicken seroconversion to SLEV, detected by enzyme immunoassay and confirmed by plaque-reduction neutralization test, was detected during August 28–November 9, with a total of 9 seroconversions in 104 chickens (8.7% seropositive) ( 10 , 11 ). WNV seropositive chicken serum samples were also reported starting on August 28, but with fewer (n = 6 [5.7%] of serum specimens tested) seroconversions to WNV than to SLEV.…”

Section: The Studymentioning

confidence: 93%

Reemergence of St. Louis Encephalitis Virus, California, 2015

White¹,

Symmes²,

Sun³

et al. 2016

Emerg. Infect. Dis.

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“…Some confirmatory assays for scFv JL427 and IgM 2G9 neutralizing activity and control assays for study of host cell artifacts were run in Dr. Sudhir Paul’s lab. Neutralization of irrelevant viruses (West Nile, Dengue II, St. Louis encephalitis) was measured from the number of plaques formed in Vero African Green Monkey kidney cells infected in the absence or presence of antibodies (41). …”

Section: Methodsmentioning

confidence: 99%

Antibodies to a Superantigenic Glycoprotein 120 Epitope as the Basis for Developing an HIV Vaccine

Planque¹,

Mitsuda²,

Nishiyama³

et al. 2012

The Journal of Immunology

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Failure to induce synthesis of neutralizing antibodies to the CD4 binding determinant (CD4BD) of gp120, a central objective in HIV vaccine research, has been alternately ascribed to insufficient immunogen binding to antibodies in their germline variable (V) region configuration expressed as B cell receptors, insufficient adaptive mutations in antibody variable (V) regions and conformational instability of gp120. We employed peptide analogs of gp120 residues 421-433 (CD4BDcore) to identify antibodies produced without prior exposure to HIV (constitutive antibodies). The CD4BDcore peptide was recognized by single chain Fv (scFv) fragments from non-infected humans with lupus that neutralized genetically diverse strains belonging to various HIV subtypes. Replacing the framework (FR) segments of a VH4-family scFv with the corresponding VH3-family FRs from scFv JL427 improved the CD4BDcore peptide binding activity, suggesting a CD4BDcore binding site outside the pocket formed by the complementarity determining regions. Replacement mutations in the FR site vicinity suggested the potential for adaptive improvement. A very small subset of serum CD4BDcore-specific serum IgAs from non-infected humans without autoimmune disease isolated by epitope-specific chromatography neutralized the virus potently. A CD4BDcore-specific, HIV neutralizing murine IgM with heavy and light chain V regions (VH and VL regions) free of immunogen-driven somatic mutations was induced by immunization with a CD4BDcore peptide analog containing an electrophilic group that binds B cells covalently. The studies indicate broad and potent HIV neutralization by constitutive antibodies as an innate, germline-encoded activity directed to the superantigenic CD4BDcore epitope that is available for amplification for vaccination against HIV.

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High Throughput Quantitative Colorimetric Microneutralization Assay for the Confirmation and Differentiation of West Nile Virus and St. Louis Encephalitis Virus

Cited by 15 publications

References 9 publications

Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

Reemergence of St. Louis Encephalitis Virus, California, 2015

Antibodies to a Superantigenic Glycoprotein 120 Epitope as the Basis for Developing an HIV Vaccine

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