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


ABSTRACT: 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.

SUBMITTER: Rogers TF 

PROVIDER: S-EPMC5892203 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Rogers Thomas F TF   Goodwin Eileen C EC   Briney Bryan B   Sok Devin D   Beutler Nathan N   Strubel Alexander A   Nedellec Rebecca R   Le Khoa K   Brown Michael E ME   Burton Dennis R DR   Walker Laura M LM  

Science immunology 20170801 14


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 cl  ...[more]

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