Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality.

Science Translational Medicine
Sonia MaciejewskiTheodore C Pierson

Abstract

The emergence of Zika virus (ZIKV) in the Americas stimulated the development of multiple ZIKV vaccine candidates. We previously developed two related DNA vaccine candidates encoding ZIKV structural proteins that were immunogenic in animal models and humans. We sought to identify neutralizing antibody (NAb) properties induced by each vaccine that correlated with protection in nonhuman primates (NHPs). Despite eliciting equivalent NAb titers in NHPs, these vaccines were not equally protective. The transfer of equivalent titers of vaccine-elicited NAb into AG129 mice also revealed nonequivalent protection, indicating qualitative differences among antibodies (Abs) elicited by these vaccines. Both vaccines elicited Abs with similar binding titers against envelope protein monomers and those incorporated into virus-like particles, as well as a comparable capacity to orchestrate phagocytosis. Functional analysis of vaccine-elicited NAbs from NHPs and humans revealed a capacity to neutralize the structurally mature form of the ZIKV virion that varied in magnitude among vaccine candidates. Conversely, sensitivity to the virion maturation state was not a characteristic of NAbs induced by natural or experimental infection. Passive transfe...Continue Reading

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Aug 12, 2020·Human Vaccines & Immunotherapeutics·Victória Alves Santos LunardelliDaniela Santoro Rosa
Sep 14, 2021·PloS One·Chayawat PhatihattakornBoonrat Tassaneetrithep
Jan 10, 2022·Molecular Therapy : the Journal of the American Society of Gene Therapy·Arun SankaradossEaswaran Sreekumar

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