title: Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: a two-year follow-up study.
abstract: BACKGROUND
  The inactivated Vero cell-derived vaccine (JE-VC, IXIARO) has replaced the traditional mouse brain-derived preparations (JE-MB) in travelers' vaccinations against Japanese encephalitis. We showed recently that a single JE-VC dose efficiently boosts immunity in JE-MB-primed vaccinees, and that JE-VC elicits cross-protective immunity against non-vaccine genotypes, including the emerging genotype I. While these studies only provided short-term data, the present investigation evaluates the longevity of seroprotection in the same volunteers.
  
  
  METHODS
  The study comprised 48 travelers who had received (1) JE-VC primary series, (2) JE-MB primary series followed by a single JE-VC booster dose, or (3) JE-MB primary series and a single JE-MB booster dose. Serum samples were collected two years after the last vaccine dose, and evaluated with the plaque-reduction neutralization test against seven Japanese encephalitis virus strains representing genotypes I-IV. PRNT50 titers ≥ 10 were considered protective.
  
  
  RESULTS
  Two years after the primary series with JE-VC, 87-93% of the vaccinees proved to be cross-protected against test strains representing genotypes II-IV and 73% against those of genotype I. After a single homologous or heterologous booster dose to JE-MB-primed subjects, the two-year seroprotection rates against genotype I-IV strains were 89-100%.
  
  
  CONCLUSIONS
  After JE-VC primary series, seroprotection appeared to wane first against genotype I. The first booster should not be delayed beyond two years. In JE-MB-primed subjects, a single JE-VC booster provided cross-protective immunity against genotype I-IV strains in almost all vaccinees, suggesting an interval of two years or even longer for the second booster. These data further support the use of a single JE-VC dose for boosting JE-MB immunity.
authors.affiliation: Haartman Institute, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Elina O
authors.initials: EO
authors.lastname: Erra
authors.affiliation: Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, Stockholm, Sweden.
authors.forename: Helena Hervius
authors.initials: HH
authors.lastname: Askling
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.affiliation: Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, Stockholm, Sweden; Centre for Clinical Research, Sörmland County Council, Eskilstuna, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
authors.affiliation: Aava Travel Clinic, Aava Medical Centre, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Riutta
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Sirkka
authors.initials: S
authors.lastname: Vene
authors.affiliation: Karolinska Institutet, Department of Medicine/Huddinge, Unit for Infectious Diseases, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lindquist
authors.affiliation: Haartman Institute, Faculty of Medicine, University of Helsinki, Helsinki, Finland; HUSLAB, Division of Virology and Immunology, Helsinki University Central Hospital, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Vapalahti
authors.affiliation: Haartman Institute, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Aava Travel Clinic, Aava Medical Centre, Helsinki, Finland; Department of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: anu.kantele@hus.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007117:Immunization, Secondary; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D057236:Travel Medicine; D014611:Vaccination; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines
keywords: Booster; Cross-protection; Duration of protection; GI; GII; GIII; GIV; GMT; GV; Ixiaro; JE; JEV; Japanese encephalitis; Japanese encephalitis virus; PRNT; Vaccine; genotype I; genotype II; genotype III; genotype IV; genotype V; geometric mean titer; plaque-reduction neutralization test