Immunogenesis in Lassa fever and prospects for vaccine development

Abstract

Analysis of literature data on the structure of the Lassa virus genome and its strain diversity has shown that the molecular heterogeneity of strains is essential in the design of vaccines and evaluation of their efficacy, which is determined by the relevant WHO recommendations. During virus reproduction, Lassa counteracts cellular immunogenesis by suppressing the expression of the suppressor of signaling proteins, cytokines and the RLR receptor that recognizes viral two-segmented RNA. The GP protein, which determines the pathogen's infectivity and tropism, should be the main target for vaccines being developed. Other targets are the processes of viral RNA synthesis that determine the features of immunogenesis. A study of the immunogenesis of Lassa fever shows that the preferred candidate would be a replicating apathogenic vaccine capable of inducing an optimal combination of cellular and humoral responses, that is, causing high activity of T-lymphocytes and the production of viral neutralizing antibodies. One of the most important characteristics of a live candidate vaccine should be genetic stability to exclude reversion to a more pathogenic genotype. Of the more than 130 candidate vaccines against Lassa fever designed, only two being the most promising were tested for immunogenicity and safety in humans (a recombinant on the measles virus platform and a DNA vaccine). A recombinant of Lassa virus with vesicular stomatitis virus and reassortants of Mopeya and Lassa viruses (MOPV/LASV- ML29) and (r3ML29) are promising for further development. A candidate vaccine rVSVG/LVGPC, similar in design to the rVSVG-ZEBOV-GP vaccine against Ebola, is promising.