Current research for a vaccine against Lassa hemorrhagic fever virus

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

Taking advantage of closely related arenaviruses, another more recent vaccine candidate was designed using gene reassortments from their bisegmented RNA genomes. 48 A reassortant virus (ML29) was subsequently generated by rationally combining the non-pathogenic L RNA from MOPV and the S RNA from LASV Josiah. 49 In addition, there were several lab-adapted mutations that led to further attenuation of the ML29 strain. 50 Studies in strain 13 guinea pigs vaccinated with the ML29 vaccine were completely protected from lethal LASV infection (Josiah and LASV-803213) up to 30-days post-vaccination. 51 Of note, these animals had undetectable virus in the blood and tissues as found by conventional plaque assay and qRT-PCR, indicating that sterilizing immunity was achieved. These initial studies showed that despite the significant genomic heterogeneity between outbreak strains, a universal vaccine for LASV might be achievable. In addition, the ML29 vaccine was able to provide up to 80% protection when given 2 days after a lethal challenge. 51 The ML29 vaccine has also undergone some testing in small NHPs, Marmosets in particular, and achieved 100% protection with accompanying sterilizing immunity. 52 However, further testing in the gold standard models for LASV disease, rhesus or cynomolgus macaques, is warranted. ML29 also has substantial safety concerns with regards to the genetic stability of a recombinant virus as well as safety in HIV-infected individuals within LASV endemic regions. 32