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Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.

Publication ,  Journal Article
Aliota, MT; Dudley, DM; Newman, CM; Mohr, EL; Gellerup, DD; Breitbach, ME; Buechler, CR; Rasheed, MN; Mohns, MS; Weiler, AM; Barry, GL ...
Published in: PLoS Negl Trop Dis
December 2016

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.

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Published In

PLoS Negl Trop Dis

DOI

EISSN

1935-2735

Publication Date

December 2016

Volume

10

Issue

12

Start / End Page

e0005168

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Viral Proteins
  • Tropical Medicine
  • Sequence Alignment
  • Molecular Sequence Data
  • Male
  • Macaca mulatta
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Aliota, M. T., Dudley, D. M., Newman, C. M., Mohr, E. L., Gellerup, D. D., Breitbach, M. E., … O’Connor, D. H. (2016). Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques. PLoS Negl Trop Dis, 10(12), e0005168. https://doi.org/10.1371/journal.pntd.0005168
Aliota, Matthew T., Dawn M. Dudley, Christina M. Newman, Emma L. Mohr, Dane D. Gellerup, Meghan E. Breitbach, Connor R. Buechler, et al. “Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.PLoS Negl Trop Dis 10, no. 12 (December 2016): e0005168. https://doi.org/10.1371/journal.pntd.0005168.
Aliota MT, Dudley DM, Newman CM, Mohr EL, Gellerup DD, Breitbach ME, et al. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques. PLoS Negl Trop Dis. 2016 Dec;10(12):e0005168.
Aliota, Matthew T., et al. “Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.PLoS Negl Trop Dis, vol. 10, no. 12, Dec. 2016, p. e0005168. Pubmed, doi:10.1371/journal.pntd.0005168.
Aliota MT, Dudley DM, Newman CM, Mohr EL, Gellerup DD, Breitbach ME, Buechler CR, Rasheed MN, Mohns MS, Weiler AM, Barry GL, Weisgrau KL, Eudailey JA, Rakasz EG, Vosler LJ, Post J, Capuano S, Golos TG, Permar SR, Osorio JE, Friedrich TC, O’Connor SL, O’Connor DH. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques. PLoS Negl Trop Dis. 2016 Dec;10(12):e0005168.

Published In

PLoS Negl Trop Dis

DOI

EISSN

1935-2735

Publication Date

December 2016

Volume

10

Issue

12

Start / End Page

e0005168

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Viral Proteins
  • Tropical Medicine
  • Sequence Alignment
  • Molecular Sequence Data
  • Male
  • Macaca mulatta
  • Humans
  • Female