Over the 50 years since its discovery, many properties of the Marburg virus have been studied, but no reliable medical remedies of preventing and treating the infection it causes have been developed, although it can potentially cause large-scale epidemics. Marburg fever is relevant due to the risk of importation to other countries. The source of infection in nature is bats (reservoir) and monkeys (intermediate host), and the routes of transmission are aerosol, contact and alimentary. The mortality rate in recent outbreaks has reached 90%. In convalescents the causative agent was identified in tears, semen, and liver biopsies weeks and months after recovery. The lack of therapeutic and prophylactic antiviral drugs, high rates of mortality, infectivity, the ability of aerosol contamination, and a high epidemic potential all together define Marburg fever as a serious global threat to international health. The development of medical protection against this infection should be an urgent task of ensuring the biological safety of the population of the Russian Federation. The most promising ways to develop vaccines against Marburg fever are the construction of recombinants based on adenovirus, vesicular stomatitis virus or alphavirus replicon, DNA vaccines. A reliable protective effect of the chemotherapy drug remdesivir in combination with human antibodies, as well as an etiotropic drug with an antisense mechanism of action and an interferon inducer has been shown. In model experiments with pseudovirus, fundamentally new ways of developing pathogen inhibitors were found preventing its exit from cells, as well as the construction of anti-gene-binding Fab fragments that inhibit the synthesis of viral RNA.
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.
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