NIH-developed Zika vaccine improves fetal outcomes in animal model

A vial of the NIAID Zika virus investigational DNA vaccine, taken at the NIAID Vaccine Research Center’s Pilot Plant in Frederick, Maryland. NIAID

An experimental Zika vaccine lowered levels of virus in pregnant monkeys and improved fetal outcomes in a rhesus macaque model of congenital Zika virus infection, according to a new study in Science Translational Medicine. 

The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators from the University of California, Davis; Duke University, Durham, North Carolina; and the University of California, Los Angeles. NIAID scientists developed the experimental vaccine and currently are evaluating it in a Phase 2 human clinical trial. The vaccine uses a small circular piece of DNA, or plasmid, containing genes that encode Zika virus surface proteins to induce an immune response.

Zika virus is primarily transmitted to humans by Aedes mosquitoes; it also can be transmitted through sex. The virus can cause serious birth defects in babies born to mothers who become infected during pregnancy. Ideally, the authors note, a Zika vaccine would be given to adolescents and adults of childbearing age before pregnancy to prevent congenital Zika syndrome.

Large outbreaks of Zika virus in the Americas in 2015 and 2016 led to thousands of cases of congenital Zika syndrome, prompting NIAID scientists to quickly develop and begin clinical trials of the NIAID DNA Zika vaccine. While clinical trials can yield data on safety and how the vaccine performs in recipients, due to the diminished incidence of Zika, conducting a clinical trial that would determine the vaccine’s ability to prevent adverse fetal outcomes has been logistically difficult. Therefore, researchers developed a macaque model of congenital Zika syndrome to provide another way to evaluate the experimental vaccine.

Their study compared outcomes in 12 unvaccinated pregnant macaques and 13 macaques vaccinated before pregnancy. All macaques were exposed to Zika virus a total of three times during the first and second trimesters. Vaccinated animals had a significant reduction in the amount of Zika virus in the blood and in the length of time virus was detectable compared to unvaccinated animals. The vaccinated group was significantly less likely to transmit Zika virus to the fetus, whereas persistent Zika virus infection in unvaccinated macaques was associated with fetal infection. No cases of early fetal loss occurred in the vaccinated group, which also had no evidence of damage 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, according to the authors. They note that the ability of a vaccine to prevent persistent Zika virus infection may be an important consideration for future clinical research. Meanwhile, the animal model can be used to learn more about Zika virus transmission from mother to fetus and possible intervention strategies.

Experts highlight Ebola vaccine progress and suggest next steps

Despite promising advances, important scientific questions remain unanswered in the effort to develop a safe and effective Ebola vaccine, according to members of an international Ebola research consortium.

April 3, 2017: Study volunteer receives an inoculation at Redemption Hospital in Monrovia, Liberia on the opening day of PREVAC, a Phase 2 Ebola vaccine trial in West Africa. NIAID

In a Viewpoint published in The Lancet, the experts review the current field of Ebola vaccine candidates and clinical trials and highlight key gaps in knowledge that need to be addressed by future research.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are among the Viewpoint’s authors. All authors are with the Partnership for Research on Ebola VACcination (PREVAC). In addition to NIAID, the partnership, established in 2017, comprises experts from the French National Institute of Health and Medical Research (Inserm), the London School of Hygiene & Tropical Medicine (LSHTM), the West African Clinical Research Consortium and their collaborators. PREVAC is currently conducting a Phase 2 clinical trial in Guinea, Liberia, Sierra Leone and Mali to evaluate three Ebola vaccination strategies in people one year and older.

Ebola virus disease remains a public health threat — the Democratic Republic of the Congo (DRC) already has experienced two Ebola outbreaks in 2018 —  underscoring the need for continued efforts to develop an effective vaccine. The authors note that 36 trials of Ebola vaccine candidates have been completed and another 14 are active, according to clinicaltrials.gov. The rVSV-ZEBOV experimental vaccine, which has been deployed in the DRC, is the only candidate with some clinical efficacy data, which were obtained in a clinical trial in Guinea conducted during the 2014-2016 Ebola outbreak in Guinea.

After reviewing the status of four additional vaccine candidates under study (Ad26.ZEBOV, MVA-BN-Filo, chAd3-EBO-Z, and the GamEvac-Combi vaccine), the authors highlight areas where more research is required. Specifically, they note the need for more data in pregnant women, children and immunocompromised populations, including people infected with HIV and the elderly. Additionally, they say more research is needed on the durability and rapidity of immune responses generated by various vaccine approaches. The experts also call for studies to identify reliable correlates of protection (the specific and measurable part of an immune response that would indicate a person is protected from Ebola) as well as large-scale trials to fully evaluate the safety and efficacy of experimental vaccines.

The authors conclude by underscoring the value of embedding social science research in clinical trial design to help build trust and engagement with the affected communities. They note that in addition to the need to investigate various vaccines and vaccination strategies to respond more effectively to future outbreaks, improving the global capacity to conduct clinical research and forming collaborative partnerships, such as PREVAC, are crucial for success.