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

• Published in: Science (American Association for the Advancement of Science) Vol. 353; no. 6301; pp. 823 - 826
• Main Authors: Stettler, Karin, Beltramello, Martina, Espinosa, Diego A., Graham, Victoria, Cassotta, Antonino, Bianchi, Siro, Vanzetta, Fabrizia, Minola, Andrea, Jaconi, Stefano, Mele, Federico, Foglierini, Mathilde, Pedotti, Mattia, Simonelli, Luca, Dowall, Stuart, Atkinson, Barry, Percivalle, Elena, Simmons, Cameron P., Varani, Luca, Blum, Johannes, Baldanti, Fausto, Cameroni, Elisabetta, Hewson, Roger, Harris, Eva, Lanzavecchia, Antonio, Sallusto, Federica, Corti, Davide
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 19.08.2016; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibodies, Viral - therapeutic use; Antibody Specificity; Cross Reactions; Dengue fever; Dengue virus; Dengue Virus - immunology; Disease Models, Animal; Flavivirus; Humans; Immune response; Immunodominant Epitopes - immunology; Immunologic Memory; In vitro testing; Lymphocytes; Mice; Monoclonal antibodies; Neutralizing; Protein Structure, Tertiary; Proteins; Public health; T-Lymphocytes - immunology; Vector-borne diseases; Viral diseases; Viral Envelope Proteins - immunology; Viral Nonstructural Proteins - immunology; Viruses; Zika virus; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control; Zika Virus Infection - therapy
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaf8505

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 l/ll (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.