Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice.

Sapparapu G, Fernandez E, Kose N, Bin Cao , Fox JM, Bombardi RG, Zhao H, Nelson CA, Bryan AL, Barnes T, Davidson E, Mysorekar IU, Fremont DH, Doranz BJ, Diamond MS, Crowe JE
Nature. 2016 540 (7633): 443-447

PMID: 27819683 · PMCID: PMC5583716 · DOI:10.1038/nature20564

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.

MeSH Terms (28)

Africa Americas Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Antibody Specificity Asia B-Lymphocytes Disease Models, Animal Epitope Mapping Female Fetal Diseases Fetus Humans Infectious Disease Transmission, Vertical Male Mice Models, Molecular Placenta Pregnancy Protein Multimerization Survival Rate Viral Proteins Viral Vaccines Virus Replication Zika Virus Zika Virus Infection

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