Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

Matthew T Aliota, Dawn M. Dudley, Christina M. Newman, Emma L. Mohr, Dane D. Gellerup, Meghan E. Breitbach, Connor R. Buechler, Mustafa N. Rasheed, Mariel S. Mohns, Andrea M. Weiler, Gabrielle L. Barry, Kim L. Weisgrau, Josh A. Eudailey, Eva G. Rakasz, Logan J. Vosler, Jennifer Post, Saverio Capuano, Thaddeus G. Golos, Sallie R. Permar, Jorge E. OsorioThomas C. Friedrich, Shelby L. O’Connor, David H. O’Connor

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Background: Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. Methodology/Principal Findings: Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. Conclusions/Significance: An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.

Original languageEnglish (US)
Article numbere0005168
JournalPLoS neglected tropical diseases
Volume10
Issue number12
DOIs
StatePublished - Dec 2 2016
Externally publishedYes

Bibliographical note

Funding Information:
This project would not have been possible without the support of a supplement to NIH grant 1R01AI116382-01A1. Research reported in this publication was also supported in part by the Office Of The Director, National Institutes of Health under Award Number P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2016 Aliota et al.

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