Heterologous protection against Asian Zika virus challenge in rhesus macaques

Summary 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. Highlights African 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.