title: Long-term immunogenicity and safety of inactivated Hantaan virus vaccine (Hantavax™) in healthy adults.
abstract: BACKGROUND
  Hemorrhagic fever with renal syndrome is a serious health problem in Eurasian countries, including Korea and China. This study evaluated the long-term immunogenicity and safety of formalin-inactivated Hantaan virus vaccine (Hantavax™).
  
  
  METHODS
  A phase III, multi-center clinical trial was undertaken to evaluate the immunogenicity and safety of Hantavax™ (three-dose schedule at 0, 1, and 13 months) among healthy adults. Immune response was assessed using the plaque reduction neutralizing antibody test (PRNT) and immunofluorescent antibody assay (IFA). Antibody levels were measured pre-vaccination and at 2, 13, 14, 25, 37, and 49 months after the initial vaccination. Systemic and local adverse events were assessed.
  
  
  RESULTS
  A total of 226 healthy subjects aged 19-75 years were enrolled. Following two primary doses of Hantavax™, the seroconversion rate was 90.14% by IFA, but it was only 23.24% by PRNT50. With booster administration, seropositive rates were 87.32% and 45.07% at one month post-vaccination according to IFA and PRNT50, respectively. In young adults (19-39 years), the seropositive rate according to PRNT50 reached about 60% after booster vaccination. The mean duration of seropositive response was 735 days for PRNT50 and 845 days for IFA. Solicited local and systemic adverse events occurred in 47.79% and 25.22% of study subjects, respectively, and most were grade 1.
  
  
  CONCLUSIONS
  Hantavax™ showed a booster effect and immunogenicity lasting two years with a three-dose schedule. The neutralizing antibody response was quite poor with two primary doses, so an early booster vaccination at 2-6 months might be warranted to provide timely protection to high-risk subjects.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Seoul, Republic of Korea.
authors.forename: Heung Jeong
authors.initials: HJ
authors.lastname: Woo
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Cheong
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Noh
authors.affiliation: Department of Microbiology, Institute for Viral Diseases, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Luck Ju
authors.initials: LJ
authors.lastname: Baek
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: wjkim@korea.ac.kr.
authors.forename: Woo Joo
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D018063:Hantaan virus; D006480:Hemorrhagic Fever with Renal Syndrome / Q000517:prevention & control*; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Hantaan virus vaccines; Hantavirus; Immunogenicity; NCT02360514; Safety