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In the Fight Against Zika, New Vaccines in Development

NOV 10, 2016 | BRIAN P. DUNLEAVY
As of November 2nd, Alaska remains the only US state without a confirmed case of Zika virus infection.

However, even as the mosquito-borne virus continues to spread—albeit perhaps more slowly with the onset of colder weather—new inroads are being made in its prevention and treatment. Most notably, human trials are currently underway for a couple of potential candidate vaccines, and a novel treatment approach has shown promise in mice models, just as the Centers for Disease Control and Prevention reports that the number of total confirmed cases of Zika in the country has surpassed the 4,000 mark.

“We urgently need a safe and effective vaccine to protect people from Zika virus infection as the virus continues to spread and cause serious public health consequences, particularly for pregnant women and their babies,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) said in a statement. “We are pleased to be part of the collaborative effort to advance [a] promising candidate vaccine into clinical trials.”

Indeed, with trials of a Zika RNA-based vaccine ongoing at the University of Maryland School of Medicine, researchers at the Walter Reed Army Institute of Research in Silver Spring, MD, in conjunction with NIAID, are now recruiting patients for a human clinical trial of a more “traditional” vaccine for the virus called ZPIV. They hope to enroll 75 patients in the study.

Walter Reed researchers developed the ZPIV vaccine candidate earlier this year after NIAID identified the Zika viral strain it uses as a starting point, in inactivated form. ZPIV is essentially based on the same inactivated flavivirus vaccine platform Walter Reed used to create its Japanese encephalitis vaccine, which was licensed in 2009. ZPIV has already proved effective in Zika-infected monkeys; however, that does not guarantee that human study subjects who are given the vaccine will produce antibodies against the disease.
Meanwhile, a National Institutes of Health (NIH)-funded study at Vanderbilt University and Washington University in St. Louis has identified a potential treatment for those already infected with Zika virus, although the approach is still very much in the early stages of development. In a study published online on November 7th in the journal, Nature, the researchers reported that they have isolated a human monoclonal antibody—called ZIKV-117—that in mouse models appears to “markedly reduce” Zika infection. Importantly, given the complications associated with the virus, the researchers also noted that the antibody had a protective effect on the fetuses in infected pregnant mice.

“These naturally occurring antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses,” study co-author James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, said in a statement released by the school in conjunction with the Nature publication.

For their study, Dr. Crowe and his colleagues first isolated antibodies from the blood of humans infected with Zika virus, harnessing antibodies that had been, in effect, battling various strains of the virus. They found that the collected antibodies reacted to the envelope protein on the surface of the virus, and used them to develop monoclonal antibodies, which they then tested via cell culture studies. Of all the monoclonal antibodies they developed, ZIKV-117 was the only one that broadly neutralized multiple strains of Zika, reducing disease as well as mortality and transmission from mother to fetus in the mouse models.

Of course, the use of ZIKV-117-based therapy in humans with Zika virus infection remains some time off in the future. According to Dr. Crowe, the next step will be to test if the Nature study’s results can be replicated in primate models, which more closely resemble humans than mice. Then, naturally, human trials will need to be performed.

“The remarkable potency and breadth of inhibition by ZIKV-117 has great promise as it was able to inhibit infection by strains from both Africa and America in cell culture and in animals, including during pregnancy,” study co-author Michael S. Diamond, MD, PhD, associate director of the Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University, added in the statement.
 

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition. 
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