Shields Up

Promising results bring researchers closer to Zika vaccine in humans

Image: Damrongpan Thongwat/iStock

A month after announcing that two promising vaccine candidates provided mice with complete protection against the Zika virus, a research team at Harvard Medical School and Beth Israel Deaconess Medical Center, in collaboration with scientists at Walter Reed Army Institute of Research and the University of São Paulo, now reports achieving complete protection against Zika virus in rhesus monkeys.

The findings are published online in the journal Science.

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This week, Florida officials confirmed that 14 people 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 advised pregnant women to avoid these areas, which is the first time in its history that the CDC 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, HMS professor of medicine at Beth Israel Deaconess, steering committee member at the Ragon Institute of MGH, MIT and Harvard, and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess.

“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,” he said.

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 vaccine developed by Army researchers at Walter Reed, a plasmid DNA vaccine and an adenovirus vector-based vaccine produced at Beth Israel Deaconess. All three platforms proved strikingly effective, and no adverse effects were observed.

To test the purified inactivated virus vaccine, scientists immunized eight rhesus monkeys with inactivated Zika virus and eight monkeys with a sham vaccine. Within two weeks, the immune systems of the animals given the Zika vaccine produced antibodies against the virus.

After a booster shot at four weeks, their 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 blood or other body 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 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 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 vaccine candidates should proceed as quickly as possible.

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).

Adapted from a Beth Israel Deaconess news release.