title: Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Aliota
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Dudley
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Newman
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin, United States of America.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Mohr
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Dane D
authors.initials: DD
authors.lastname: Gellerup
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Breitbach
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Connor R
authors.initials: CR
authors.lastname: Buechler
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Mustafa N
authors.initials: MN
authors.lastname: Rasheed
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Mariel S
authors.initials: MS
authors.lastname: Mohns
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Weiler
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Barry
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Weisgrau
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Josh A
authors.initials: JA
authors.lastname: Eudailey
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Logan J
authors.initials: LJ
authors.lastname: Vosler
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Post
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Saverio
authors.initials: S
authors.lastname: Capuano
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Departments of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Departments of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Thaddeus G
authors.initials: TG
authors.lastname: Golos
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.|Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000071244:Zika Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D014764:Viral Proteins