A ML29 reassortant virus protects guinea pigs against a distantly related Nigerian strain of Lassa virus and can provide sterilizing immunity

Abstract

Lassa virus (LASV) is responsible for the deaths of thousands of people in West Africa annually. Genetic diversity among LASV strains is the highest among the Arenaviridae and represents a great challenge for vaccine development. Guinea pigs vaccinated with a ML29 reassortant vaccine experienced sterilizing immunity and complete protection when challenged on day 30 either with homologous virus or with the distantly related Nigerian isolate. Simultaneous vaccination-challenge or challenge on day 2 after vaccination also protected 60-100% of the animals against both strains, but without sterilizing immunity. These results indicate that simultaneous replication of ML29 and LASV attenuates the virulence of LASV infection.

Fig. 1

Temperature, weigh and AST levels in plasma of strain 13 guinea pigs. A - C, acute LASV infection. D – F, vaccinated and challenged animals. Numbers of surviving animals to numbers of challenged animals are indicated in brackets.

Fig. 2

Viremia, viral load in tissues, and humoral immune responses in vaccinated animals. A, viremia in vaccinated and control animals at different time points after challenge with LASV-803213/NIG. B, viremia and viral load in tissues of sacrificed guinea pigs. All animals died in control group (# 3). However, RNA samples were available only from blood and tissues of 3 animals. C, IgG ELISA. Plasma samples were collected at different time points from animals vaccinated with ML29 and anti-LASV IgG antibodies were determined by ELISA. D, western blotting. Plasma samples from three ML29-vaccinated animals were collected at day 42 after vaccination and incubated with antigen blots as described in Materials and Methods. Lane 1-3, blots were probed with plasma samples from vaccinated animals; lane 4, the blot was incubated with human reconvalescent anti-LASV serum [36]. NP and GP2, positions of LASV structural proteins.