S. I. Syromyatnikova

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

Lujo hemorrhagic fever (LHF) is a viral disease accompanied with fever, headache, vomiting, diarrhea, arthralgia, myalgia and numerous signs of hemorrhagic syndrome. LHF causes a clinical syndrome remarkably similar to Lassa hemorrhagic fever. The first case of LHF occurred in Johannesburg, South Africa, in 2008. There was a secondary transmission from the index patient to four healthcare workers. Four of the five patients died. The etiologic agent of LHF is Lujo virus (LUJV) belonging to Arenavirus genus of the Arenaviridae Family. Virus Lujo is the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa during the last 40 years. Data about epidemiology, clinical characteristics and diagnostics of LHF, properties of Lujo virus (according to phylogenetic analysis), and recommended precautions for preventing secondary transmission are considered in this paper.

Ebola virus that composed Ebolavirus genus of Filoviridae Family causes severe hemorrhagic fever in humans with high case-fatality rates (up to 90%). The Ebolavirus genus includes Ebola-Zaire, Ebola-Sudan, Ebola-Reston, Ebola-Tai Forest and Ebola-Bundibugyo viruses. The date about epidemic outbreaks of disease, reservoirs of infection, accidental hosts of Ebola virus are presented in this review. The date about natural reservoirs of infection are accessed only for Ebola-Zaire and Ebola-Reston viruses. For Ebola-Sudan, Ebola-Tai Forest and Ebola-Bundibugyo viruses such information is absence. The bats are natural reservoirs for Ebola-Zaire and Ebola-Reston viruses. The formation of natural reservoirs of filoviruses assumes possibilities of existence of several hosts. The interrelation of Ebola virus and their hosts, dynamics of infection are the classical «susceptible-infected-immune» (recovered) cycle. The likely schemes of rises of epidemic outbreaks, caused by Ebola-Zaire virus are suggested.

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies. The aim of the study was to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C. Materials and methods: the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed. Results: the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches. Conclusions: the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics.