Durability and correlates of vaccine protection against Zika virus in rhesus monkeys

疫苗对寨卡病毒的保护效力持久性及其在恒河猴中的相关因素

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作者:Peter Abbink,Rafael A Larocca,Kittipos Visitsunthorn,Michael Boyd,Rafael A De La Barrera,Gregory D Gromowski,Marinela Kirilova,Rebecca Peterson,Zhenfeng Li,Ovini Nanayakkara,Ramya Nityanandam,Noe B Mercado,Erica N Borducchi,Abishek Chandrashekar,David Jetton,Shanell Mojta,Priya Gandhi,Jake LeSuer,Shreeya Khatiwada,Mark G Lewis,Kayvon Modjarrad,Richard G Jarman,Kenneth H Eckels,Stephen J Thomas,Nelson L Michael,Dan H Barouch

Abstract

An effective Zika virus (ZIKV) vaccine will require long-term durable protection. Several ZIKV vaccine candidates have demonstrated protective efficacy in nonhuman primates, but these studies have typically involved ZIKV challenge shortly after vaccination at peak immunity. We show that a single immunization with an adenovirus vector-based vaccine, as well as two immunizations with a purified inactivated virus vaccine, afforded robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination. In contrast, two immunizations with an optimized DNA vaccine, which provided complete protection at peak immunity, resulted in reduced protective efficacy at 1 year that was associated with declining neutralizing antibody titers to subprotective levels. These data define a microneutralization log titer of 2.0 to 2.1 as the threshold required for durable protection against ZIKV challenge in this model. Moreover, our findings demonstrate that protection against ZIKV challenge in rhesus monkeys is possible for at least 1 year with a single-shot vaccine.

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