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Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality.
Maciejewski, Sonia; Ruckwardt, Tracy J; Morabito, Kaitlyn M; Foreman, Bryant M; Burgomaster, Katherine E; Gordon, David N; Pelc, Rebecca S; DeMaso, Christina R; Ko, Sung-Youl; Fisher, Brian E; Yang, Eun Sung; Nair, Deepika; Foulds, Kathryn E; Todd, John Paul; Kong, Wing-Pui; Roy, Vicky; Aleshnick, Maya; Speer, Scott D; Bourne, Nigel; Barrett, Alan D; Nason, Martha C; Roederer, Mario; Gaudinski, Martin R; Chen, Grace L; Dowd, Kimberly A; Ledgerwood, Julie E; Alter, Galit; Mascola, John R; Graham, Barney S; Pierson, Theodore C.
Affiliation
  • Maciejewski S; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Ruckwardt TJ; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Morabito KM; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Foreman BM; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Burgomaster KE; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Gordon DN; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Pelc RS; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • DeMaso CR; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Ko SY; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Fisher BE; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Yang ES; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Nair D; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Foulds KE; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Todd JP; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Kong WP; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Roy V; Ragon Institute, Cambridge, MA 02139, USA.
  • Aleshnick M; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Speer SD; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Bourne N; Department of Microbiology and Immunology, Department of Pathology, Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Barrett AD; Department of Microbiology and Immunology, Department of Pathology, Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Nason MC; Biostatistics Research Branch, Division of Clinical Research, NIAID, NIH, Bethesda, MD 20852, USA.
  • Roederer M; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Gaudinski MR; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Chen GL; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Dowd KA; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Ledgerwood JE; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Alter G; Ragon Institute, Cambridge, MA 02139, USA.
  • Mascola JR; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Graham BS; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. piersontc@mail.nih.gov bgraham@mail.nih.gov.
  • Pierson TC; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA. piersontc@mail.nih.gov bgraham@mail.nih.gov.
Sci Transl Med ; 12(547)2020 06 10.
Article in En | MEDLINE | ID: mdl-32522807
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 transfer experiments in mice revealed that neutralization of mature ZIKV virions more accurately predicts protection from ZIKV infection. These findings demonstrate that NAb correlates of protection may differ among vaccine antigens when assayed using standard neutralization platforms and suggest that measurements of Ab quality, including the capacity to neutralize mature virions, will be critical for defining correlates of ZIKV vaccine-induced immunity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Viral Vaccines / Zika Virus / Zika Virus Infection Type of study: Prognostic_studies / Qualitative_research Limits: Animals Language: En Journal: Sci Transl Med Journal subject: CIENCIA / MEDICINA Year: 2020 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Viral Vaccines / Zika Virus / Zika Virus Infection Type of study: Prognostic_studies / Qualitative_research Limits: Animals Language: En Journal: Sci Transl Med Journal subject: CIENCIA / MEDICINA Year: 2020 Document type: Article Affiliation country: United States