Elina O Erra1, Helena Hervius Askling2, Sutee Yoksan3, Lars Rombo4, Jukka Riutta5, Sirkka Vene6, Lars Lindquist7, Olli Vapalahti8, Anu Kantele9. 1. Haartman Institute, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. 2. Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, Stockholm, Sweden. 3. Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand. 4. Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, Stockholm, Sweden; Centre for Clinical Research, Sörmland County Council, Eskilstuna, Sweden. 5. Aava Travel Clinic, Aava Medical Centre, Helsinki, Finland. 6. Swedish Institute for Communicable Disease Control, Solna, Sweden. 7. Karolinska Institutet, Department of Medicine/Huddinge, Unit for Infectious Diseases, Stockholm, Sweden. 8. 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. 9. 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.
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.
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.