Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection.
Stettler K., Beltramello M., Espinosa DA., Graham V., Cassotta A., Bianchi S., Vanzetta F., Minola A., Jaconi S., Mele F., Foglierini M., Pedotti M., Simonelli L., Dowall S., Atkinson B., Percivalle E., Simmons CP., Varani L., Blum J., Baldanti F., Cameroni E., Hewson R., Harris E., Lanzavecchia A., Sallusto F., Corti D.
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.