Zika Vaccine: Two Candidates Show Promise In Mice

By Dr. Francis Collins

Last February, the World Health Organization declared a public health emergency over concerns about very serious birth defects in Brazil and their possible link to Zika virus. But even before then, concerns about the unprecedented spread of Zika virus in Brazil and elsewhere in Latin America had prompted NIH-funded scientists to step up their efforts to combat this emerging infectious disease threat. Over the last year, research aimed at understanding the mosquito-borne virus has progressed rapidly, and we now appear to be getting closer to a Zika vaccine.

Zika virus (red), isolated from a microcephaly case in Brazil. The virus is associated with cellular membranes in the center. Credit: NIAID

Zika virus (red), isolated from a microcephaly case in Brazil. The virus is associated with cellular membranes in the center. Credit: NIAID

In a recent study in the journal Nature, researchers found that a single dose of either of two experimental vaccines completely protected mice against a major viral strain responsible for the Zika outbreak in Brazil [1]. Caution is certainly warranted when extrapolating these (or any other) findings from mice to people. But, taking into account the fact that researchers have already developed safe and effective human vaccines for several related viruses, the new work represents a very encouraging milestone on the road toward a much-needed Zika vaccine for humans.

The two experimental vaccines undergoing testing represent different approaches to vaccine development. One approach, developed by Dan Barouch of Beth Israel Deaconess Medical Center, Boston, and colleagues, is a DNA vaccine composed of select snippets of genetic material from a Zika strain from Brazil. The DNA included in the vaccine encodes proteins found at the viral surface that are known to induce an immune response.

Barouch and his colleagues found that a single shot of their experimental DNA vaccine could induce the production of Zika-specific neutralizing antibodies in mice. To find out whether those antibodies protected against Zika infection, they intravenously delivered live Zika virus from Brazil or Puerto Rico to mice four weeks after receiving either the vaccine or a sham shot.

Unvaccinated mice developed high levels of Zika virus that lasted about six days. In contrast, vaccinated mice showed no detectable Zika virus in their bloodstream. This was, of course, very encouraging news, demonstrating that the vaccine offered complete protection against Zika strains from both Brazil and Puerto Rico. The other good news is the vaccinated mice resisted infection for at least eight weeks.

The second vaccine, developed by a team at the Walter Reed Army Institute of Research, Silver Spring, MD, working in close collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), was produced from a purified, inactivated Zika virus from Puerto Rico. To find out whether this vaccine offered similar protection, the researchers assessed whether it was able to induce antibodies that can protect against Zika infection. The results were positive.  It will now be important to follow the animals in the coming months to assess how long Zika immunity lasts and test the vaccines in larger animals and in humans.When it comes to vaccine development, multiple options are always best. Purified, inactivated virus vaccines, such as used to develop the annual flu shot, represent a more traditional approach. But DNA vaccines, where the DNA is injected into muscle and directs the production of the relevant antigen, can offer some potential advantages. While no DNA vaccine has yet received FDA approval for human use, there is great interest in introducing this “vaccine of the future” into practice. To produce such vaccines, labs don’t have to grow large batches of virus, which can take time and money. Furthermore, these vaccines allow scientists to include only selected bits of a virus known to produce the desired immune response, with essentially zero risk of inducing an active infection.

At least two other Zika DNA vaccines under development at NIAID and elsewhere are showing promise. The NIAID will launch its first human vaccine safety tests of a DNA vaccine, involving about 80 volunteers, at the end of the summer or in the early fall. The tests will last about three months and should set the stage for a clinical trial to evaluate whether the vaccine guards against Zika infection in people.

This fall, NIAID and Walter Reed plan to launch two clinical trials of inactivated viral vaccines, including the one described in the Nature study. The trials, each involving dozens of volunteers, will test to see whether the vaccines are safe and elicit an immune response in people.

Vaccine development and testing take time. But given the rapid pace of progress, there’s now good reason for hope that a Zika vaccine could be a possibility in the not too distant future.

Reference:

[1] Vaccine protection against Zika virus from Brazil. Larocca RA, Abbink P, Peron JP, Zanotto PM, Iampietro MJ, Badamchi-Zadeh A, Boyd M, Ng’ang’a D, Kirilova M, Nityanandam R, Mercado NB, Li Z, Moseley ET, Bricault CA, Borducchi EN, Giglio PB, Jetton D, Neubauer G, Nkolola JP, Maxfield LF, Barrera RA, Jarman RG, Eckels KH, Michael NL, Thomas SJ, Barouch DH. Nature. 2016 Jun 28.