RT Journal Article SR Electronic T1 Heterologous protection against Asian Zika virus challenge in rhesus macaques JF bioRxiv FD Cold Spring Harbor Laboratory SP 059592 DO 10.1101/059592 A1 Matthew T. Aliota A1 Dawn M. Dudley A1 Christina M. Newman A1 Emma L. Mohr A1 Dane D. Gellerup A1 Meghan E. Breitbach A1 Connor R. Buechler A1 Mustafa N. Rasheed A1 Mariel S. Mohns A1 Andrea M. Weiler A1 Gabrielle L. Barry A1 Kim L. Weisgrau A1 Josh A. Eudailey A1 Eva G. Rakasz A1 Logan J. Vosler A1 Jennifer Post A1 Saverio Capuano III A1 Thaddeus G. Golos A1 M. Anthony Moody A1 Sallie R. Permar A1 Jorge E. Osorio A1 Thomas C. Friedrich A1 Shelby L. O’Connor A1 David H. O’Connor YR 2016 UL http://biorxiv.org/content/early/2016/06/17/059592.abstract AB Zika virus (ZIKV) isolates are genetically diverse, but belong to two recognized lineages, termed “African” and “Asian.” Asian ZIKV infection during pregnancy causes fetal abnormalities including microcephaly. Developing an effective preventative Zika virus vaccine that protects pregnant women is essential for minimizing fetal abnormalities; at least 18 groups are developing ZIKV vaccines (Hayden, 2016). The genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, and the degree to which immunity against one ZIKV strain could provide protection against another is unknown. Here we show that rhesus macaques infected with East African ZIKV strain MR766 are completely protected from subsequent infection with heterologous Asian ZIKV. MR766 is more genetically divergent from all known Asian ZIKV strains than Asian ZIKV strains are from one another. Therefore, ZIKV strain selection is unlikely to compromise vaccine effectiveness.HighlightsAfrican Zika virus (ZIKV) strain MR766 productively infects macaques (68 characters) Immunity elicited by MR766 protects macaques against heterologous Asian ZIKV (77 characters)In vivo restoration of a putative N-linked glycosylation site in MR766 (70 characters)Immunogen selection is unlikely to adversely affect the breadth of vaccine protection (85 characters)eTOC An effective Zika virus vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses are primed by infection with East African ZIKV are completely protected from reinfection with heterologous Asian ZIKV. Any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.