Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi, Anahita; Dahlke, Christine; Addo, Marylyn M.

In all clinical trials, VSV-EBOV was administered intramuscularly and primarily as a single-shot regimena regimen that had previously been shown to be protective soon after administration in NHP. 15, [24] [25] [26] These tested single-shot regimens are indispensable in outbreak situations, especially in volatile regions with insufficient infrastructure where follow-up vaccinations are often not possible. Yet, in comparison, prime-boost strategies utilizing VSV-EBOV may be beneficial when durability of the vaccine response needs to be expanded. First data have been gathered in a phase I trial, where a subgroup of 30 individuals received a prime-boost regimen (days 0 and 28) of VSV-EBOV at three different dose levels. The vaccinees developed higher antibody (Ab) and virus neutralization titers compared to participants who only received a single-shot; yet these observations were no longer statistically significant six months after initial vaccination. 29 Prime-boost regimens are further evaluated in ongoing studies: The PREVAC study is presently assessing a prime only as well as a prime-boost regimen (at days 0 and 56) of VSV-EBOV in comparison to other vaccine strategies in an estimated 4500 volunteers, including children from 1 year of age, with a follow-up time of 12 months. Another ongoing study, the PREPARE study investigates immune response durability and vaccine efficacy is investigated in persons at occupational risk of EBOV exposure, such as health-care workers and laboratory personnel, across a three-year timeframe. Here, participants are either vaccinated with a single shot of VSV-EBOV or receive a booster immunization 18 months after initial vaccination. In addition, participants whose antibody levels decrease beneath a predefined threshold will also be offered a booster vaccination.