By Brenda L. Mooney
SILVER SPRING, MD – A vaccine developed by Army researchers to combat Zika virus not only induced a robust immune response in trials but also was found to be safe and well-tolerated in healthy adults, according to a recent article in The Lancet.1
The report was about three Phase 1 human clinical trials evaluating a Zika purified inactivated virus vaccine (ZPIV). The studies each focused on an aspect of the vaccine, such as background immunity, vaccine dose or vaccination schedule.
“It is imperative to develop a vaccine that prevents severe birth defects and other neurologic complications in babies caused by Zika virus infection during pregnancy,” said lead author Kayvon Modjarrad, MD, PhD, of the Walter Reed Army Institute of Research (WRAIR). “These results give us hope that a safe and effective vaccine will be achievable.”
An additional trial with ZPIV is continuing in Puerto Rico, where the population has natural exposure to other flaviviruses such as dengue, researchers noted.
“A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed,” researchers wrote. “We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings.”
Three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant were conducted between Nov. 7, 2016, and Jan. 25, 2017, initially including 68 healthy adults who were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, or of 5:1 at Saint Louis University, Saint Louis and Beth Israel Deaconess Medical Center, Boston.
Vaccinations were administered intramuscularly on days 1 and 29, with a primary objective of determining the safety and immunogenicity of the ZPIV candidate. Follow up continued to day 57.
Results indicated that the vaccine caused only mild to moderate adverse events. Pain, reported by 60%, or tenderness, reported by 47%, at the injection site were the most frequent local effects reported. The most frequent systemic reactogenic events were fatigue, 43%; headache, 39%, and malaise, 22%.
Researchers reported that, by day 57, 92% of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titers seen at day 43 and exceeding protective thresholds seen in animal studies.
“The ZPIV candidate was well tolerated and elicited robust neutralizing antibody titers in healthy adults,” they concluded.
“Not only is the development of a Zika vaccine a global public health priority, but it is also necessary to protect Service Members and their families,” added Col. Nelson Michael, MD, PhD. director of WRAIR’s Military HIV Research Program and Zika program co-lead with Modjarrad.
DoD researchers set out to develop the ZPIV vaccine candidate in response to the 2015 outbreak of Zika virus in the Americas. WRAIR researchers conceived the ZPIV vaccine in February 2016 and quickly advanced the candidate to a Phase 1 human trial by November of the same year.
“WRAIR has previously steered to licensure a similar vaccine for Japanese encephalitis, a flavivirus in the same family as Zika, which helped speed our vaccine development effort,” said Leyi Lin, MD, who led one of the trials at WRAIR.
The researchers said their next steps include valuating how long vaccine-induced immunity lasts, and the impact of dose, schedule and background immunity.
- Modjarrad K, Lin L, George SL, Stephenson KE, et al. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials. The Lancet , Published:04 December 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)33106-9