Other Infections

Experimental Vaccines Demonstrate Protection Against Zika Virus in Monkey Studies

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Three different approaches using an inactivated virus vaccine, a DNA-based vaccine, and an adenovirus vector vaccine stimulated antibody production and provided complete protection against Zika virus infection in exposed rhesus monkeys, according to research published in the August 4 online edition of Science.

Parts of South America, the Caribbean, and the U.S. are currently experiencing outbreaks of Zika virus, which is primarily transmitted by mosquito bites but can also be sexually transmitted. While the virus typically does not lead to serious illness in adults, it can cause microcephaly and other fetal brain damage if a woman is infected while pregnant.

Peter Abbink and Dan Barouch from the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Centerand colleagues evaluated various vaccine platforms to see if they provided protection in rhesus monkeys exposed to Zika virus, after observing promising results in mice. Barouch's team has also done extensive work on HIV vaccine candidates.

The researchers found that apurified inactivated virus (PIV) vaccine induced production of Zika-specific binding and neutralizing antibodies within 2 weeks after a first dose, with strengthened immune responses after a second booster dose given 4 weeks later.

All 8 vaccinated monkeys exposed to Zika virus strains from Brazil and Puerto Rico were completely protected, with no detectable virus, while 8 animals given placebo injections were infected and showed high levels of virus replication for around 7 days. In addition, purified immunoglobulin (antibodies) from the vaccinated monkeys conferred passive protection to other animals that were not vaccinated themselves.

The team also found that 2 doses of a plasmid DNA vaccine and a single dose of a recombinant rhesus adenovirus vector vaccine expressing Zika pre-membrane and envelope (prM-Env) proteins also stimulated production of Zika-specific neutralizing antibodies and completely protected all exposed monkeys.

All of these approaches appeared to be well-tolerated with no notable side effects or other safety issues.

"These data support the rapid clinical development of Zika vaccines for humans," the study authors concluded.

While inactivated virus and DNA/prM-Env vaccines appeared similarly effective in mice, the purified inactivated virus approach "proved more potent than the DNA vaccine in rhesus monkeys under the conditions tested," they noted in their discussion.

Protection in mice and monkeys was observed at relatively low antibody titers that are likely achievable in humans using these methods, "thus raising optimism for the development of a Zika virus vaccine for humans," they added. However, they cautioned that future studies will need to address the potential impact of cross-reactive antibodies against dengue virus and other flaviviruses.

"Results from both mouse and nonhuman primate testing are encouraging and support a decision to move forward with our U.S. government, industry, and regulatory partners to advance our [Zika purified inactivated virus] vaccine candidate to human trials," said Col. Stephen Thomas in a press release issued by the U.S. Military HIV Research Program, which initially developed the PIV Zika vaccine and has extensive flavivirus research experience going back more than a century.

A Phase 1 clinical trial of the purified inactivated virus vaccine in humans is expected to start later this year. The Pilot Bioproduction Facility at the Walter Reed Army Institute of Research has manufactured a batch of the vaccine for clinical studies and the army has signed a cooperative agreement to transfer the technology to Sanofi Pasteur to explore larger scale manufacturing and advanced development, according to the press announcement.

8/24/16

Reference

P Abbink, RA Larocca, RA De La Barrera, DH Barouch, et al. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science. August 4, 2016 (online ahead of print).

Other Sources

U.S. Military HIV Research Program. Vaccine Candidates Protect Against Zika Virus in Rhesus Monkeys. Press release. August 3, 2016.

National Institute of Allergy and Infectious Diseases. Three Vaccine Approaches Protect Monkeys Against Zika Infection. Press release. August 4, 2016.