PITTSBURGH, Oct. 3, 2016 - Two vaccines against Zika virus developed at the University of Pittsburgh School of Medicine have successfully conveyed immunity from female mice to pups conceived weeks after the mother's vaccination.
When challenged with Zika virus within a week of their birth, both vaccines protected the pups against neurological damage better than pups with no maternal-conferred immunity. The results are published online today and scheduled for the November issue of EBioMedicine, a journal supported by Cell Press and The Lancet.
"We've not only developed a promising vaccine candidate to move toward larger preclinical and, eventually, human clinical trials, but also a delivery format that would be inexpensive to produce and distribute to hundreds of thousands of people," said senior author Andrea Gambotto, M.D., associate professor of surgery in Pitt's School of Medicine.
Zika is a virus spread primarily through the bite of an infected mosquito of the Aedes species. When pregnant women are infected, the virus can pass to their fetus, which can damage the developing baby and cause severe neurological birth defects, including microcephaly, or an abnormally small head.
One of the two vaccines uses a "microneedle array" to deliver the vaccine just below the surface of the skin through tiny crystals that dissolve after being affixed to the skin by a Band-Aid-like patch. The technology was co-invented by Louis D. Falo, M.D., Ph.D., chair of Pitt's Department of Dermatology and co-author of the study.
The other vaccine uses the traditional needle delivery format and adenovirus, a type of common cold virus, to present Zika antigens to the immune system to induce immunity.
Both vaccines used proteins on the "envelope," or outer shell, of the virus as the antigen to prime the immune system so it can quickly recognize and fight off the actual virus. This approach has worked in the past to develop West Nile, yellow fever and dengue vaccines.
Three groups of female mice, with five mice per group, were immunized with either one of the two vaccines or a saline solution with no vaccine for the control group. Two weeks after the initial vaccination, the mice received a booster of the same vaccine they originally received.
Blood tests were performed at vaccination and every two weeks afterward. The mice showed immunity against Zika two weeks after immunization with the adenovirus Zika vaccine and six weeks after immunization with the microneedle array Zika vaccine.
Five weeks after initial immunization, the female mice were mated with unvaccinated males. Because mice do not develop microcephaly, giving the mothers Zika while pregnant would be unlikely to affect the pups. So the researchers waited until one week after the pups were born and then exposed them to Zika. All of the pups from the mothers immunized with adenovirus Zika vaccine and half of the pups from the mothers who received the microneedle array vaccine survived infection. Only 12.5 percent of the pups from mothers in the unimmunized control group survived.
Furthermore, all of the control group pups showed signs of neurological damage, including loss of balance, muscle weakness and hind-limb paralysis. Five out of six of the microneedle array group pups also exhibited neurological issues, though they weren't as severe as the control group's symptoms. None of the adenovirus vaccine pups showed significant neurological problems.
Although the adenovirus Zika vaccine definitely performed better in this study, Dr. Gambotto said it was used as a proof-of-principle vaccine in mice to quickly develop and test if the envelope protein antigen would work in a mouse model. It wouldn't work well in humans because the vast majority of us have already had adenovirus colds so our immune systems would simply neutralize the vaccine and not develop proper Zika antibodies.
"We decided to move forward with the microneedle array Zika vaccine and have since developed a promising, second-generation vaccine," said Dr. Gambotto. "We are hopeful, now that Congress has approved the $1.1 billion bill to provide funding for Zika prevention and research, that we'll be able to do larger-scale studies to evaluate and develop this vaccine for possible human clinical trials in the future."
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Additional researchers on this study are Eun Kim, Ph.D., Geza Erdos, Ph.D., Shaohua Huang, Ph.D., and Thomas Kenniston, M.S., all of Pitt.
UPMC and Pitt's Department of Surgery provided funding for this study.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
Contact: Allison Hydzik
Phone: 412-647-9975
E-mail: HydzikAM@upmc.edu
Contact: Arvind Suresh
Phone: 412-647-9966
E-mail: SureshA2@upmc.edu
Journal
EBioMedicine