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.

• Three dose primary Hantavax® immunization was immunogenic. • Hantavax® vaccination showed a booster effect. • Revised 3 + 1 vaccination schedule can provide rapid protection against hantavirus infection. • Adverse events did not increase with repeated vaccinations. 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. 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. 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. 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). [ABSTRACT FROM AUTHOR]