Comparison of African, Asian, and American Zika Viruses in Swiss Webster mice: Virulence, neutralizing antibodies, and serotypes

The sequence of Zika virus has evolved as it has spread out of Africa and into the Americas. It is unclear whether American strains of the virus define a new serotype. Here, we have tested the virulence and immunogenicity of three wild-type ZIKV strains in neonatal Swiss Webster mice. We found that all three ZIKV strains (African MR766, 1947; Asian FSS13025, 2010; and American, PRVABC59, 2015) are capable of killing neonatal mice after intracranial injection. Intraperitoneal injection with these viruses did not kill, but produced neutralizing antibodies as measured by a PRNT50 assay. Sera from mice infected with each virus were tested for neutralizing activity against the infecting virus and also the other two viruses by a PRNT50 assay. In general, the antibodies induced by each virus were good at neutralizing that virus (the homologous virus), but somewhat poorer at neutralizing the other two viruses (heterologous viruses). Antibodies induced by the African strain MR766 were about 4-fold worse at neutralizing the American strain PRVABC59 than the homologous strain, while antibodies induced by the American strain were about 10-fold worse at neutralizing the African strain than the homologous strain. Because the antibodies are cross-neutralizing at some level, the viruses do not form separate serotypes. Nevertheless, these results raise concern that the immunity conferred by the African virus may protect only relatively poorly against the new American strains. This has implications for the possible spread of the American ZIKV strains to Africa and Southeast Asia, and also for the development of vaccines.