Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors

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Science Immunology  18 Aug 2017:
Vol. 2, Issue 14, eaan6809
DOI: 10.1126/sciimmunol.aan6809

For zika virus, experience counts

For the immune system, practice makes perfect. Previous exposure to an infection elicits a stronger, faster memory response. But how does the immune system respond to a similar but not identical infection? Rogers et al. tracked the neutralizing antibody response to zika virus infection in individuals with and without previous exposure to the closely related dengue viruses. They found that zika virus infection primed the preexisting dengue virus response, but that this cross-reactive response was poorly neutralizing. In contrast, de novo zika virus responses were potently neutralizing. These data suggest that zika virus vaccines should target epitopes not present in dengue virus subtypes.


Zika virus (ZIKV) shares a high degree of homology with dengue virus (DENV), suggesting that preexisting immunity to DENV could affect immune responses to ZIKV. We have tracked the evolution of ZIKV-induced B cell responses in three DENV-experienced donors. The acute antibody (plasmablast) responses were characterized by relatively high somatic hypermutation and a bias toward DENV binding and neutralization, implying the early activation of DENV clones. A DENV-naïve donor in contrast showed a classical primary plasmablast response. Five months after infection, the DENV-experienced donors developed potent type-specific ZIKV neutralizing antibody responses in addition to DENV cross-reactive responses. Because cross-reactive responses were poorly neutralizing and associated with enhanced ZIKV infection in vitro, preexisting DENV immunity could negatively affect protective antibody responses to ZIKV. The observed effects are epitope-dependent, suggesting that a ZIKV vaccine should be carefully designed for DENV-seropositive populations.

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