Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Journal article

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.

Authors: Stettler, K; Beltramello, M; Espinosa, D; Graham, V; Cassotta, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science
• Volume: 353
• Issue: 6301
• Pages: 823-826
• Publication date: 2016-08-01
• Acceptance date: 2016-07-05
• DOI: 10.1126/science.aaf8505
• EISSN: 1095-9203
• ISSN: 0036-8075
• Pmid: 27417494
• Language: English
• Keywords: Zika virus infection; antibodies; dengue virus; immunologic memory; T-lymphocytes; xross reactions; Zika virus