During 2000–2022, a total of 69 of Russia’s 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (10⁵ popul.). European Russia reported 162,045 (98.5%) cases in 53/60 regions with 9.7 cases/10⁵ popul. Asian Russia reported 2535 (1.5%) cases in 16/25 regions with 0.6 cases/10⁵ popul. In the same period, Russia reported 668 (0.4%) fatal HFRS cases, and 4030 (2.4%) cases among children under the age of 14 years. Most HFRS cases occurred during autumn and winter. The incidence among rural residents was 6.7 per 10⁵ popul., higher than the urban 4.4 per 10⁵ popul.; however, among HFRS patients, rural and urban residents account for 35% and 65%, respectively. Six hantaviruses, causing HFRS of different clinical severity, were recognized as pathogens: Hantaan (HTNV) and Amur (AMUV) of Orthohantavirus hantanense species, Seoul (SEOV) of Orthohantavirus seoulense species, Puumala (PUUV) of Orthohantavirus puumalaense species, and Kurkino (KURV) and Sochi (SOCV) of Orthohantavirus dobravaense species, with the principal hosts Apodemus agrarius coreae, Apodemus peninsulae, Rattus norvegicus, Myodes glareolus, Apodemus agrarius agrarius, and Sylvaemus ponticus, respectively. It was found that 97.7% of HFRS cases are caused by PUUV, therefore, this virus plays the main role in the HFRS morbidity structure in Russia.

Hemorrhagic fever with renal syndrome (HFRS) is the most common natural focal disease in the Russian Federation with about 6–12 thousand cases annually. 97.7% of all HFRS cases in Russia are caused by the Puumala virus, 1.5%—by the Hantaan, Amur, Seoul viruses, and about 0.8% by the Kurkino and Sochi viruses. There are no licensed vaccines for the prevention of HFRS in the European Region; there are no specific therapeutic to treat orthohantavirus infections. Here we report the results of candidate polyvalent HFRS vaccine preclinical studies. The vaccine was produced on the basis of three viruses: Puumala, strain PUU-TKD/VERO, Hantaan, strain HTN-P88/VERO, and Sochi, strain DOB-SOCHI/VERO. These viruses were inactivated with β-propiolacton, purified by gel filtration and aluminum hydroxide adsorbed. 18–20 g female BALB/c mice were immunized intramuscularly 2 or 3 times with a 2-week intervals and blood was taken 2 weeks after immunization. FRNT₅₀ performed for virus specific antibodies determination. ELISA kits (Bender MedSystems, Cusabio) were used for detection of cytokines IL-1β, IL-12, INF-ɣ. Neutralizing antibodies geometric mean titers to the Puumala, Hantaan, and Sochi viruses were: 9.22 ± 0.31, 9.17 ± 0.26, 8.96 ± 0.34 log₂/ml. Up to 1/32 vaccine dilution neutralizing antibodies were identified in 10/10 immunized mice with titers ≥ 3,32 log₂/ml. IL-12 and INF-ɣ increased after immunization in average 5.5 and 2.8 times respectively, that reflects the Th1 type immunity stimulation. IL-1β slightly increased, that may suggest vaccine low reactogenicity. According to our preclinical investigations, the candidate polyvalent HFRS vaccine elicits balanced immune response to the Puumala, Hantaan and Sochi viruses.

In the Russian Federation, the vaccine against hemorrhagic fever with renal syndrome is at the stage of preclinical and clinical trials. The aim of the study was to analyze an effect of vaccine schedule on neutralizing antibodies (nAB) dynamics in guinea pig models applied with experimental Puumala virus based hantavirus vaccine (HV). Quantitative evaluation of neutralizing antibodies was presented as antibody titer geometric mean expressed in binary logarithms (log₂) by the 50% reduction of focus-forming units (FRNT₅₀) in Vero cell in the focus reduction neutralization test. The HV dual inoculation to guinea pigs was carried out in 14 day intervals, booster injection was applied on day 182 after the onset, in the thigh muscle tissue by using 0.3 ml undiluted (HV-u/d) and in the 1/10 dilution (HV-1/10). nAB titer on day 14 after the first HV-u/d and HV-1/10 injection was measured to be at titer of 5.5±0.3 and 4.8±0.3, respectively. After the second injection, the nAB peak was as high as 9±0.2 on day 42 after the first HV-u/f injection, and 6.5±0.2 on day 14 after the HV-1/10 injection. nAB decreased down to 6.2±0.3 and 5±0.3, respectively, on day 364 after the first injection. The booster HV-u/d and HV-1/10 injection induced increase in nAB up to 9.5±0.3 and 6.5±0.3, respectively. After the booster injection, it induced significantly higher nAB observed on day 238 after the first HV-u/d injection and delayed up to the 294 day for the HV-1/10. The results of the study indicated the early formation of the immune response, long-term nAB persistence and significantly enhanced immune response after the booster injection on day 182, which indicated a potential for the booster injection a year later. The immunological efficacy and protective activity of the vaccine schedule may be finally assessed according to the results of clinical trials.

Relevance. Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common natural focal diseases of viral etiology In Russia. The medical and social significance of these two infections is determined by the extensive fociof their spread, high annual morbidity rates in the population, and the possibility of developing severe forms of the disease leading to permanent disability and death. The causative agents of HFRS In Russia are 6 types of hantaviruses Hantaan, Amur, Seoul, Puumala, Kurkino and Sochi, which, immunologically and genetically significantly different from each other, support their existence in nature through six different species of small mammals, which are sources of infection in humans. TBE virus strains that cause disease in humans belong to five phylogenetically distinct subtypes, including: Far Eastern, European, Siberian, “178-79” and Baikal. Aim. Analysis of the role of small mammals and ticks in the ecology of HFRS and TBE pathogens. Conclusions. Small mammals retain and transmit hantaviruses to uninfected animals and ticks. At the same time, ticks retain and transmit to ticks and mammals not only the TBE virus, but also hantaviruses. Despite the taxonomic difference between the viruses that cause HFRS and TBE, some of their ecological properties are similar.

Hemorrhagic fever with renal syndrome (HFRS) is the most common zoonotic disease in Russia, with about a 98% abundance of Puumala virus in all HFRS cases. We report clinical manifestations and genomic characteristics of the Puumala virus strain that caused an unconventional course of HFRS with sudden death. The patient was admitted to the hospital on the third day from fever onset with hyperthermia, cough, shortness of breath, and severe weakness, and died 28 h after hospitalization despite intensive care. Further analyses of autopsy samples led to Puumala virus detection. The viral genome was sequenced, followed by phylogenetic and similarity plot analyses. The genomic sequences of three viral segments were identified as endemic for the Moscow region strain. Phylogenetic and similarity plot analysis revealed the reassortant origin of the strain via M segment exchange. This finding increases the explored molecular diversity of Puumala virus in the Central Federal District and underscores the need for heightened awareness of HFRS manifestations that deviate from regular clinical presentation.