Immunogenicity and safety of a modified three-dose priming and booster schedule for the Hantaan virus vaccine (Hantavax): A multi-center phase III clinical trial in healthy adults

Background: Hemorrhagic fever with renal syndrome is a serious health problem in Eurasian countries. This study aimed to evaluate the immunogenicity and safety of formalin-inactivated Hantaan virus vaccine (Hantavax®) with a 3 + 1 vaccination schedule. Methods: A phase III, multi-center clinical trial was conducted to evaluate the immunogenicity and safety of Hantavax® (three primary doses and a booster dose schedule at 0, 1, 2 and 13 months) among healthy adults. Immune responses were assessed using the plaque reduction neutralizing antibody test (PRNT) and immunofluorescent antibody assay (IFA). Systemic and local adverse events were assessed. Results: A total of 320 healthy subjects aged ≥19 years were enrolled. Following three primary doses of Hantavax®, the seroconversion rate was 80.97% and 92.81% by PRNT and IFA, respectively. With booster administration, seropositive rates were 67.47% and 95.68% at one-month post-vaccination according to PRNT and IFA, respectively. Solicited local and systemic adverse events were reported in 30.50–42.81% and 16.67–33.75% during the three primary dose vaccination, while those were reported 36.57% and 21.36% after the booster doses. Both local and systemic adverse events did not increase with repeated vaccinations. Conclusion: Hantavax® showed a high seroconversion rate after the three-dose priming, and additional dose administration with 11-month interval induced good booster effects. (ClinicalTrials.gov Identifier: NCT02553837).