The respiratory syncytial virus (RSV) fusion (F) glycoprotein prefusion conformation is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies which were substantially more potent than the prophylactic antibody palivizumab. The co-crystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed that D25 locks F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed two other antibodies, AM22 and 5C4, also bind to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and guide new approaches for passive prevention of RSV-induced disease.

Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector expressing ZIKV prM-Env also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.