Science Translational Medicine
13 December 2017 Vol 9, Issue 420
Durability and correlates of vaccine protection against Zika virus in rhesus monkeys
By 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
Science Translational Medicine13 Dec 2017 Full Access
Not all vaccines afford robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination
Patience pays off
As an individual may not encounter the pathogen for years after they have been vaccinated, efficacious vaccines typically require induction of long-lasting immunity. Abbink and colleagues vaccinated nonhuman primates with one of several candidate Zika virus vaccines and then waited an entire year before conducting a viral challenge. These vaccines had all shown promising results in previous experiments with a more immediate challenge, but here, one vaccine faltered, likely due to waning antibodies. The researchers performed more experiments to suggest that circulating antibodies are mediating protection for these vaccines. These results are useful for Zika virus vaccine development and instructive for vaccine development in general.
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.