Preclinical investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH) and collaborators from the University of California, Davis, Duke University, and the University of California, Los Angeles, have developed an experimental Zika virus vaccine that is currently being assessed in a Phase II clinical trial. This specific vaccine utilizes a small circular piece of DNA (plasmid), containing genes that encode Zika virus surface proteins to induce an immune response.
The Zika Challenge
Zika virus is a real problem in many parts of the world. It is transmitted to humans via Aedes mosquitos, but can also be transmitted through sex and cause serious birth defects in babies born to mothers who become infected during pregnancy. The study authors are seeking to have a treatment for adolescents and adults of childbearing age before pregnancy to prevent congenital Zika syndrome.
There were large outbreaks of the virus in the Americas in 2015 and 2016, leading to thousands of cases of congenital Zika syndrome–promoting NIAID scientists to get to work on a vaccine.
Challenge with Human Trials & Macaque Model for Preclinical Research
Because of the diminished incidences of Zika, conducting a clinical trial that would help determine the vaccine’s ability to prevent fatal outcomes represents a significant logistical challenge. Hence, the research team developed a macaque model of congenital Zika syndrome, and thus, ultimately found a way to evaluate the experimental vaccine in primates.
The study compared outcomes in 12 unvaccinated pregnant macaques and 13 macaques vaccinated before pregnancy. All 25 macaques were exposed to the Zika virus for a total of three times during the first and second trimesters. The vaccinated animals had a significant reduction in the amount of Zika virus in their blood and in the length of time the virus was detectable compared to the unvaccinated animals.
The team reported that the group of primates who were vaccinated were less likely to transmit the Zika virus to the fetus, whereas the Zika virus infection in unvaccinated macaques was associated with fetal infection to either the placenta or the fetal brain.
The study suggests that sterilizing immunity—an immune response that prevents infection entirely, with no detectable virus, may not be required for significant protection against congenital Zika syndrome. They believe that it will be important for clinical investigators to consider the ability of a vaccine to prevent persistent Zika virus infection in contemplating future clinical trials. In the interim, the NIAID led group believes the animal model can be leveraged for ongoing learning about Zika virus transmission from mother to fetus and possible intervention strategies.
Anthony S. Fauci, MD, NIAID Director
Barney S. Graham, MD, PhD, Deputy Director NIAID’s Vaccine Research Center
Theodore C. Pierson, PhD, chief of NIAID’s Laboratory of Viral Diseases
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