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Zika Virus Specific Diagnostic Epitope Discovery
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Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.

Rajeshwer S Sankhala1, Vincent Dussupt2, Gina Donofrio2

  • 1Emerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.

Cell Reports
|August 10, 2023
PubMed
Summary
This summary is machine-generated.

Researchers identified Zika virus (ZIKV)-specific antibodies that neutralize the virus without enhancing dengue virus (DENV) disease. These findings are crucial for developing safe and effective ZIKV vaccines and therapeutics.

Keywords:
CP: ImmunologyX-ray crystallographyZika virusdengue virusflavivirusmonoclonal antibodiesneutralizing antibodiesrhesus macaquestructural biology

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Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • Zika virus (ZIKV) causes severe congenital defects.
  • Cross-reactivity between ZIKV and dengue virus (DENV) complicates vaccine development due to potential antibody-dependent enhancement.
  • Identifying ZIKV-specific antibody targets is vital for safe vaccine design.

Purpose of the Study:

  • To classify ZIKV-specific antibody targets.
  • To develop neutralizing monoclonal antibodies (mAbs) against ZIKV that do not cross-react with DENV.
  • To understand the antigenic landscape of ZIKV for vaccine and therapeutic strategies.

Main Methods:

  • Isolation of ZIKV-reactive B cells and monoclonal antibodies (mAbs) from ZIKV-infected rhesus macaques.
  • Grouping of mAbs into distinct antigenic groups targeting ZIKV envelope glycoprotein.
  • Co-crystal structure determination of mAb-ZIKV envelope glycoprotein complexes.
  • Serological identification of antibody specificities in convalescent human populations.

Main Results:

  • Four distinct antigenic groups of ZIKV-specific mAbs were identified, targeting unique epitopes on the envelope glycoprotein.
  • Structural analysis revealed novel epitope targets, including cross-protomer and dimer-dimer interactions.
  • All four identified specificities were found in humans who recovered from ZIKV infection.
  • Representative mAbs from all groups conferred protection against ZIKV in mouse models.

Conclusions:

  • This study provides critical insights into ZIKV-specific antigenicity, differentiating it from DENV.
  • The identified ZIKV-specific epitopes are valuable targets for developing next-generation vaccines and therapeutics.
  • The findings support the development of safe ZIKV vaccines that avoid antibody-dependent enhancement.