Immune response evaluation in the guinea pigs after immunization with the experimental Puumala virus vaccine

Abstract

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 5.50.3 and 4.80.3, respectively. After the second injection, the nAB peak was as high as 90.2 on day 42 after the first HV-u/f injection, and 6.50.2 on day 14 after the HV-1/10 injection. nAB decreased down to 6.20.3 and 50.3, respectively, on day 364 after the first injection. The booster HV-u/d and HV-1/10 injection induced increase in nAB up to 9.50.3 and 6.50.3, 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.