Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Sci Transl Med. 2017 Dec 13;9(420). doi: 10.1126/scitranslmed.aao4163.
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.
一种有效的寨卡病毒（ZIKV）疫苗将需要长期持久的保护。几种寨卡病毒疫苗候选物在非人类灵长类动物中显示出了保护效力，但这些研究通常涉及在接种后不久、免疫高峰期时进行寨卡病毒挑战。我们表明，单次接种基于腺病毒载体的疫苗，以及两次接种纯化的灭活病毒疫苗，在接种后 1 年可在恒河猴中提供针对寨卡病毒挑战的强大保护。相比之下，两次接种优化的 DNA 疫苗在免疫高峰期提供了完全的保护，但在 1 年后保护效力降低，与中和抗体滴度下降到亚保护水平有关。这些数据将中和滴度的对数 titer 定义为 2.0 到 2.1，作为该模型中抵抗寨卡病毒挑战所需的持久保护的阈值。此外，我们的研究结果表明，在恒河猴中，单次接种疫苗至少可以在 1 年内预防寨卡病毒挑战。
