Despite Challenges, Hope Remains for Zika Vaccine

Caroline Helwick

October 28, 2016

NEW ORLEANS — Although researchers are facing many challenges, there are reasons for optimism about a Zika vaccine, according to Mark Mulligan, MD, director of the Hope Clinic of the Emory Vaccine Center in Atlanta, Georgia.

The main reason is the success seen with other licensed flavivirus vaccines, the development of which can serve as a useful platform for the development of a Zika vaccine, he said here at IDWeek 2016.

Dr Mulligan reported that a live attenuated yellow fever vaccine has been administered to "billions" of people at risk; a live chimeric dengue vaccine has been licensed in a half dozen countries; and a candidate for a West Nile virus DNA vaccine has shown promise in phase 2 trials.

What is not clear, however, is whether a Zika vaccine will prevent viremia. "This is absolutely critical for the prevention of infection in pregnancy," said Dr Mulligan. "If a woman becomes viremic while pregnant, she may seed the placenta or the fetus. We must prevent viremia, whether through a vaccine, a drug, or a monoclonal antibody."

Part of the difficulty is that the detection of viruses in the body is time sensitive, he explained. "We can design prospective studies, but to actually measure reductions in viremia is difficult."

One approach under consideration is a human-challenge model, in which study participants are vaccinated and then challenged with Zika or placebo. "This would be one way to obtain a viremia signal," but there are bioethical hurdles, he acknowledged.

Another issue is the timely deployment of a vaccine. In the past, epidemics have waned before a vaccine was ready. "We would like to have countermeasures in place before this happens," Dr Mulligan pointed out.

In addition, the target group must be identified. A key lesson from the rubella virus epidemic in the mid 1960s is that targeted vaccination is far less effective than widespread immunization. Therefore, Zika vaccination of a broad, at-risk population is probably warranted.

The priority, when supplies are limited, will be to vaccinate women of childbearing age and their sexual partners, because "Zika is a sexually transmitted disease," he emphasized. When the supply allows, the "congenital rubella paradigm" will probably be followed for people living in areas where Zika is endemic or in areas where there is an epidemic outbreak. The vaccine will also be beneficial to travelers and commercial sex workers in such areas.

"Robust Pipeline" of Vaccines

Fortunately, a Zika vaccine will likely have broadly neutralizing activity against a single viral serotype. "We think a single vaccine should protect against all serotypes, genotypes, and strains," Dr Mulligan reported.

The Zika DNA vaccine candidate being developed by the Vaccine Research Center at the National Institutes of Health has proven protective in nonhuman primates. A placebo-controlled phase 2b study of 2400 people will be initiated early next year at 30 sites in the Caribbean, Central and South America, and, if warranted, the southern United States.

A study of another DNA vaccine, delivered using electroporation, is in a phase 1 trial in Canada and the United States and in a phase 2 trial in Puerto Rico. The study will recruit a subset of adults seropositive for the dengue virus, which will yield information about a very different immunologic environment, he added.

Four human studies of a purified inactivated-virus Zika vaccine plus alum, produced by Walter Reed Army Institute, which has already proved protective in nonhuman primates, will soon begin.

One study will evaluate an accelerated vaccination schedule, and the other three phase 1 trials will evaluate efficacy in flavivirus-naive patients, in dengue-experienced patients, and in people vaccinated against yellow fever virus and Japanese encephalitis virus. "These will get at the issue of whether preexisting flavivirus immunity alters response," Dr Mulligan explained.

"This product is being transferred to Sanofi Pasteur," he noted. "We have Big Pharma engaging in this effort."

Dr Mulligan said he is encouraged by recent findings that three different vaccine platforms against the Zika virus were shown to be protective in rhesus monkeys. "It's a robust pipeline," he said, "and there are many more than the ones I have described."

Urgent Need

There is an urgent need for protection against the Zika virus, in the form of vaccines and therapeutics, because there are no effective antiviral medications, said Daniel McQuillen, MD, from the Lahey Hospital and Medical Center in Burlington, Massachusetts, who is IDWeek program chair for the Infectious Diseases Society of America.

There is also an urgent need for better control of the vector. The impact of the virus has been minimal so far in the United States, but the potential for risk is real, he noted.

"Much work is needed in the management of the vector, which is the same in the southern United States as in South America. While this summer we saw little impact, we are probably going to see a big outbreak next summer in the southern states unless we put more effort into control," Dr McQuillen predicted. "It certainly will happen here."

"We don't have a crystal ball, but there will probably be more risk," said Pablo Tebas, MD, from the Hospital of the University of Pennsylvania in Philadelphia.

"It's nerve-wracking, especially for women and their male partners, who may be shedding virus for 6 months. It seems that if you contract Zika, you are protected from future infections for life. That's what we are hoping for with a vaccine," Dr Tebas explained.

Dr Mulligan reports that Emory University holds stock in GeoVax, which is developing a Zika vaccine. Dr McQuillen and Dr Tebas have disclosed no relevant financial relationships.

IDWeek 2016. Presented October 26, 2016.

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