Current research for a vaccine against Lassa hemorrhagic fever virus

Warner, Bryce M; Safronetz, David; Stein, Derek R

With the potential of widespread use of VSV-EBOV in the wake of the West African Ebola outbreak, an important aspect to consider would be the potential for an increase in pre-existing immunity to the VSV backbone. A deployment of a second VSV-based vaccine in the region, mainly VSV-LASV-GPC, may not provide adequate immunogenicity and protection. Marzi et al sought to address this concern by designing consecutive LASV and EBOV studies in cynomolgus macaques. 62 Initially, three macaques were vaccinated with VSV-LASV-GPC and then challenged with a lethal dose of LASV Josiah. All three animals survived the challenge with no overt signs of disease and no virus was detected in the blood. Additionally, two animals showed no signs of seroconversion after challenge, suggesting near-sterilizing immunity. A single control animal was infected in parallel, which rapidly succumbed to classical LASV disease on Day 13. The same three surviving animals were then vaccinated with a dose of VSV-EBOV-GPC and subsequently challenged with a lethal dose of EBOV 28 days later. Despite having significant VSV antibody titers prior to VSV-EBOV-GPC vaccination, all immunized animals survived the challenge, while a single control animal succumbed to EBOV disease on Day 7. More importantly, this study shows that the VSV vector has the potential to be used repeatedly for the protection of both EBOV and LASV infection in Africa. The VSV recombinant system is extremely robust and has the potential to express and tolerate the expression of multiple transgenes. The combination of both EBOV and LASV glycoprotein expression in a single vaccine is feasible and has significant potential to prevent future outbreaks of EBOV and LASV in West Africa.