Vaccine Candidates Protect Primates Against Zika Viru

Promising results lead to optimism that a Zika vaccine will likely be feasible

BOSTON – A month after announcing that two promising vaccine candidates provided mice with complete protection against the Zika virus, a research team at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Walter Reed Army Institute of Research (WRAIR) and the University of São Paulo, now reports achieving complete protection against Zika virus in rhesus monkeys. The research team’s findings were published online today in the journal Science.

This week Florida officials confirmed that fourteen people have contracted the Zika virus in Miami-Dade and Broward Counties, the first-known mosquito-borne transmission in the continental United States. The Centers for Disease Control and Prevention (CDC) recommended that pregnant women avoid these areas, which is the first time in history that it has recommended avoiding travel to regions within the continental United States. Because Zika infection in pregnant women has been shown to lead to fetal microcephaly and other major birth defects, developing a safe vaccine is an urgent global health priority.

“Three vaccines provided complete protection against Zika virus in nonhuman primates, which is the best animal model prior to starting clinical trials,” said senior author Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC, Professor of Medicine at Harvard Medical School, and Steering Committee Member at the Ragon Institute of MGH, MIT and Harvard. “The consistent and robust protection against Zika virus in both rodents and primates fuels our optimism about the development of a safe and effective Zika vaccine for humans.”

Vaccines work by stimulating the immune system to develop defenses against the virus. The researchers tested three means of producing Zika immunity in rhesus monkeys: a purified inactivated virus (PIV) vaccine developed by Army researchers at WRAIR and a plasmid DNA vaccine and an adenovirus vector-based vaccine produced at BIDMC. All three platforms proved strikingly effective, and no adverse effects were observed.

To test the PIV vaccine, scientists immunized eight rhesus monkeys with inactivated Zika virus and eight monkeys with a sham vaccine. Within two weeks, the animals’ immune systems produced antibodies against the virus. After a booster shot at four weeks, the antibody levels increased substantially. When these animals were exposed to two strains of infectious Zika virus from Brazil and Puerto Rico, they showed complete protection against the virus, with no detectable Zika virus in the blood or other bodily secretions.

In a second experiment, 12 rhesus monkeys were immunized with either a DNA vaccine or an adenovirus vector-based vaccine. These types of vaccines introduce only a fragment of Zika virus DNA coding for the Zika virus’ outer coat into the body. These vaccines led the immune system to develop antibodies. In this study, both vaccines produced Zika-specific antibodies in all primates tested, with the adenovirus vector-based vaccine provoking a broader and a more potent antibody response. When the primates were exposed to the Brazilian strain of Zika virus, both vaccines provided complete protection. These data suggest that clinical trials for these Zika virus vaccine candidates should proceed as quickly as possible.

Study coauthors include the following members of the Barouch Laboratory at BIDMC: Peter Abbink (co-first author), Rafael A. Larocca (co-first author), Christine A. Bricault, Edward T. Moselyey, Michael Boyd, Marinela Kirilova, Zhenfeng Li, David Ng’ang’a, Ovini Nanayakkara, Ramya Nityanandam, Noe B. Mercado, Erica N. Borducchi, Arshi Agarwal, Amanda L. Brinkman, Crystal Cabral, Abishek Chandrashekar, Patricia B. Giglio, David Jetton, Jessica Jimenez, Benjamin C. Lee, Shanell Mojta, Katherine Malloy, Mayuri Shetty, George H. Neubauer, and Katherine E. Stephenson.

Coauthors from Walter Reed Army Institute of Research include Rafael A. De La Barrera, Kayvon Modjarrad, Richard G. Jarman, Kenneth H. Eckels, Nelson L. Michael and Stephen J. Thomas. Coauthors from the University of Sao Paulo, Brazil, include Jean Pierre S. Peron and Paolo M. De A. Zanotto.

This work was funded by grants from the U.S. Military Research and Materiel Command and the U.S. Military HIV Research Program through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-11-2-0174); the National Institutes of Health (AI095985, AI096040, AI100663, AI124377); the Ragon Institute of MGH, MIT, and Harvard; and the São Paulo Research Foundation (FAPESP 2011/18703-2, 2014/17766-9).