Journal
SCIENCE
Volume 353, Issue 6301, Pages 823-826Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf8505
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Funding
- European Union [HEALTH-F3-2011-281803]
- European Research Council [323183 PREDICT]
- Swiss National Science Foundation [160279]
- U.S. National Institutes of Health [R01 AI24493]
- Ministero della Salute, Fondazione IRCCS Policlinico San Matteo, Ricerca Corrente [8020615]
- Helmut Horten Foundation
- SNF [310030_166445]
- Lions Club Monteceneri
- Swiss National Science Foundation (SNF) [310030_166445] Funding Source: Swiss National Science Foundation (SNF)
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Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV-cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Memory T cells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.
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