WRAIR has been studying flaviviruses for more than 100 years. By leveraging its international research infrastructure and extensive infectious disease expertise, the Institute was able to respond quickly to the Zika threat by developing a promising preventive vaccine.
In the midst of the 2016 Zika virus epidemic, WRAIR — working in synchrony with other government agencies, academic institutions and industry partners — developed a Zika Purified Inactivated Virus (ZPIV) vaccine candidate, advancing it from initial concept to Phase 1 clinical trials within nine months.
Institute researchers decided to move forward with the purified inactivated virus vaccine because it builds on a type of vaccine that has been licensed before. It is the same technology WRAIR used to develop its Japanese encephalitis vaccine, which was licensed in 2009.
Its comprehensive product development infrastructure and an international network of laboratories positioned WRAIR to be able to respond quickly to Zika. Prior to the Zika outbreak of 2016, WRAIR’s expeditionary laboratory in Thailand had already been conducting biosurveillance for Zika for several years, an effort that gave the Institute a head-start on vaccine development efforts.
WRAIR’s in-house capabilities have enabled EIDB to quickly advance a vaccine candidate. The Institute’s Pilot Bioproduction Facility, then headed by Dr. Kenneth H. Eckels, produced more than 1,500 doses of the vaccine candidate that were used for the preclinical studies and has manufactured a vaccine lot for use in initial (small) human clinical studies. WRAIR’s Clinical Trials Center was the initial site that tested the vaccine in humans.
EIDB began human trials for its ZPIV candidate at WRAIR’s Clinical Trials Center in late 2016. Additional human trials took place in the United States, supported by the National Institute of Allergy and Infectious Diseases (NIAID), through its Vaccine and Treatment Evaluation Units and with University of Puerto Rico/Saint Louis University in Ponce, PR. These additional studies evaluated the vaccine in different populations and compared dosing and vaccination schedules.
Promising Preclinical Findings
In June 2016 WRAIR and collaborators at Harvard University completed a promising preclinical study of the ZPIV vaccine, the findings of which were published in the journal Nature and demonstrated that single shots of the vaccine protected mice against subsequent Zika challenge.
Findings from another preclinical study in rhesus monkeys showed that the ZPIV candidate induced both binding and neutralizing antibodies in the two weeks after initial vaccination, which were substantially boosted following a second ZPIV dose given at week four. After being experimentally infected with Zika virus, vaccinated monkeys showed complete protection against both Brazilian and Puerto Rican strains of Zika virus as evidenced by no detectable virus in blood, urine and secretions after exposure. The study was published in the journal Science in August 2016.