Current research for a vaccine against Lassa hemorrhagic fever virus

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

In 1987, the first successful vaccine directed against LASV was described. A recombinant vaccinia virus (Lister strain) was engineered to express the NP from LASV and given to outbred Hartley guinea pigs. 46 Animals that received the recombinant virus showed no signs of disease, and no virus was isolated from the blood after challenge with 1×10 4 TCID50 of LASV strain GA391 (Nigerian isolate). All control animals succumbed to infection between Days 14 and 16. Interestingly, a similar dose of the prototypical strain Josiah, a Sierra Leone isolate, is generally only 10%-20% lethal in Hartley guinea pigs, which highlights the significant diversity and pathogenic heterogeneity of LF. A second study using a guinea pig-adapted version of Josiah confirmed the protective efficacy of various recombinant strains of vaccinia expressing either LASV NP or GPC with 94% and 79% protection, respectively. 47 In contrast to the initial vaccinia experiments, most animals including the recombinant vaccine vaccinated animals showed some signs of disease with mild fever and acute viremia that was 10-fold less than control animals. Interestingly, a combination of NP and GPC vaccinia viruses led to a poorer outcome with only 58% protection. A set of secondary comprehensive studies was undertaken in rhesus and cynomolgus macaques to test the individual vaccinia vaccines expressing GP1, GP2, and NP. 31 Ninety percent of animals that received all three proteins survived a lethal LASV challenge (n=10). Of considerable interest was that all animals that received the individual proteins succumbed to infection (GP1, GP2, or NP; 0% survival). This is in stark contrast to the previous guinea pig experiments and despite all macaques generating robust anti-NP antibody responses. In addition, all animals that received a combination of GP1 and GP2 survived indicating that both proteins are independently integral for protection against lethal disease. These initial studies, combined with the failure of whole-inactivated LASV to protect against lethal infection, 41 indicate a GPC-specific cell-mediated component to LASV protection.