A single dose of VSV-Ebola virus vaccine—approximately one-millionth of what is in the vaccine being used in the outbreak outbreak in the Democratic Republic of the Congo (DRC)—remains fully protective against disease in experimentally infected monkeys, according to National Institutes of Health scientists.
The NIH investigators completed the vaccine dosage study using cynomolgus macaques and an updated vaccine component to match the EBOV Makona strain that circulated in West Africa from 2014-16. The study appears in Lancet’s EBioMedicine.
Nearly 250,000 people have received the investigational
VSV-EBOV vaccine since August 2018 as part of a “ring vaccination” program to
help stem the outbreak. The vaccine appears to be safe and highly effective.
The manufacturer has announced that it has submitted a biologics license
application to the U.S. Food and Drug Administration. VSV-EBOV is based on a
live-attenuated vesicular stomatitis virus and delivers an EBOV protein to
elicit protective immune responses. With the continued need to vaccinate
individuals in the DRC and surrounding countries, a potential shortage of
VSV-EBOV vaccine is a concern and further dose adjustment is a possible
Scientists from NIH’s Rocky Mountain Laboratories (RML),
part of the National Institute of Allergy and Infectious Diseases, tested
several dosage strengths, including one with 10 million plaque-forming units
(PFU). They determined that a vaccine with 10 PFUs was just as effective as the
highest dose tested (a dose which was still lower than the one currently in use
in the DRC). They vaccinated macaques 28 days prior to infecting them with a
lethal dose of EBOV and then monitored the animals for 42 days after
infection. Even the macaques given the
lowest dose appeared completely protected from disease due to EBOV.
The scientists say their study findings could help make
more vaccine available for more people and may reduce adverse reactions to the
vaccine because of the smaller amount of active ingredient. Such reactions
can include injection site irritation, headache, fatigue, fever, chills,
myalgia, and arthralgia. Demonstrating that the vaccine appears effective with
adjusted dosing also could ease the burden on vaccine production.
The authors say that although results from preclinical and clinical
studies can differ, these promising findings in macaques of complete protection
with a lower-dose VSV-EBOV vaccine help support the possibility of similar
clinical trials in people.
A Marzi et al. Single
low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola
challenge. EBioMedicine DOI: 10.1016/j.ebiom.2019.09.055 (2019).