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Pre-Clinical Studies of Inactivated Polyvalent HFRS Vaccine

2020; Frontiers Media; Volume: 10; Linguagem: Inglês

10.3389/fcimb.2020.545372

2235-2988

Dzagurová Tk, Alexandra A. Siniugina, Aydar A. Ishmukhametov, М. С. Егорова, С. С. Курашова, М. В. Баловнева, Andrei A. Deviatkin, Е. А. Ткаченко, О. А. Леонович, Evgeny A. Tkachenko,

Viral Infections and Outbreaks Research

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 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 3 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 sorbed. 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 the cytokines IL-1β, IL-12, INF-ɣ detection. 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 in titer ≥ 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 candidate polyvalent HFRS vaccine elicits harmonious immune response to the Puumala, Hantaan and Sochi viruses.