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

Abstract

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy1. 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.

Preventing Neonatal Herpes Infections Through Maternal Immunization

“…Recent studies show that maternal antibodies can transfer into the developing peripheral and central nervous system during gestation [11,18]. These findings coupled with reports that maternal antibodies are effective against congenital Zika [19] and cytomegalovirus [20] infections suggest a broader applicability of maternal immunizations to other TORCH pathogens.…”

Recent advances in human flavivirus vaccines

“…However, the sudden ZIKV outbreak in South America alerted health authorities and the public to develop a vaccine. Preclinical studies have demonstrated a protective role of CD8 T cells and antibodies against ZIKV infection, the latter being sufficient for complete protection [67][68][69][70]. However, cocirculation of DENV, WNV and ZIKV has been reported in several countries and previous studies suggested an immunological cross-reactivity between viruses, which may drive immune-mediated enhancement [71][72][73].…”

Zika Virus: Current Status, Protective Vaccine Trials, and Antiviral Treatment Alternatives

“…Zika virus enfeksiyonlarına için spesifik tedaviler henüz deneme aşamasındadır. Yakın zamanda yayımlanan bir makalede, araştırmacılar insan monoklonal antikorların (ZIKV-117) Zika virus kökenlerini hücre kültürü ve fare modelinde (gebelik süreci de dâhil olmak üzere) nötralize ettiğini gösterdiler (46) . Konvelesan serum veya plazmanın enfeksiyona karşı koruyucu özellik-leri de araştırılmış ve umut verici sonuçlar elde edilmiştir (13) .…”