Immunogenicity and Reactogenicity of a Monovalent Inactivated 2009 Influenza A Vaccine in Adolescents: With Special Reference to Pre-Existing Antibody

Published:November 17, 2011DOI:


      To evaluate the immunogenicity and reactogenicity of a monovalent 2009 pandemic influenza vaccine in Japanese adolescents.

      Study design

      A total of 111 junior high school and high school students aged 13 to 18 years participated. Subjects received two doses of a monovalent inactivated unadjuvanted 2009 influenza A vaccine. Immunogenicity of the vaccine was evaluated according to the international criteria. We also asked subjects to report adverse reactions.


      After the first dose of vaccine, the seroprotection rate was 91% (95% CI, 85%-96%), the seroconversion rate was 78% (70%-86%), and the geometric mean titer ratio was 11.9 in all subjects. Antibody titers achieved did not differ significantly after the first and the second doses. With multivariate analysis, an independent negative effect of a prevaccination titer of ≥1:40 on ≥4 fold antibody increase was indicated. No serious adverse reaction was reported.


      The monovalent pandemic vaccine generally was safe, and a single dose of the vaccine given to adolescents induced sufficient immunity. Pre-existing antibody showed substantial effect on antibody response. The effect of pre-existing titer should be considered when evaluating the immunogenicity of influenza vaccines, especially in studies conducted during pandemic waves.
      GMT (Geometric mean titer), GMTR (Geometric mean titer ratio), H1N1 (Influenza A), HAI (Hemagglutination-inhibition), ORS (Oculo-respiratory syndrome)
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        • World Health Organization
        New influenza A/H1N1 virus: global epidemiological situation, June 2009.
        Wkly Epidemiol Rec. 2009; 84: 249-257
        • Greenburg M.E.
        • Lai M.H.
        • Hartel G.F.
        • Whichems C.H.
        • Gittleson C.
        • Bennet J.
        • et al.
        Response to a monovalent 2009 influenza A (H1N1) vaccine.
        N Engl J Med. 2009; 361: 2405-2413
        • Zhu F.C.
        • Wang H.
        • Fang H.H.
        • Yang J.G.
        • Lin X.J.
        • Liang X.F.
        • et al.
        A novel influenza A (H1N1) vaccine in various age groups.
        N Engl J Med. 2009; 361: 2414-2423
        • Plennevaux E.
        • Sheldon E.
        • Blatter M.
        • Reeves-Hoché M.K.
        • Denis M.
        Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomized controlled phase 2 trials.
        Lancet. 2010; 375: 41-48
        • Liang X.F.
        • Wang H.Q.
        • Wang J.Z.
        • Fang H.H.
        • Wu J.
        • Zhu F.C.
        • et al.
        Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccine in China: a multicenter, double-blind, randomized, placebo-controlled trial.
        Lancet. 2010; 375: 56-66
        • Jain S.
        • Kamimoto L.
        • Bramley A.M.
        • Schmitz A.M.
        • Benoit S.R.
        • Louie J.
        • et al.
        Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.
        N Engl J Med. 2009; 361: 1935-1944
        • Hirst G.K.
        The quantitative determination of influenza virus and antibodies by means of red cell agglutination.
        J Exp Med. 1942; 75: 49-64
        • Hirota Y.
        • Kaji M.
        • Ide S.
        • Goto S.
        • Oka T.
        The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age.
        Vaccine. 1996; 14: 1597-1602
        • Hobson D.
        • Baker F.A.
        • Curry R.L.
        Effect of influenza vaccines in stimulating antibody in volunteers with prior immunity.
        Lancet. 1973; 2: 155-156
      1. Global Influenza Programme, World Health Organization [WHO Internet resources]. Geneva: WHO 2002. WHO Manual on Animal Influenza Diagnosis and Surveillance. Available at Accessed September 1, 2011.

        • Skowronski D.M.
        • Jacobsen K.
        • Daigneault J.
        • Remple V.P.
        • Gagnon L.
        • Daly P.
        • et al.
        Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts.
        Pediatrics. 2006; 117: 1963-1971
        • European Committee for Proprietary Medical Products
        Note for guidance on harmonisation of requirements for influenza vaccines (CPMP/BWP/214/96).
        European Agency for the Evaluation of Medical Products, London1997
        • Center for Biologics Evaluation and Research
        Guidance for industry: clinical data needed to support the licensure of pandemic influenza vaccines.
        Food and Drug Administration, Bathesda, MD2007
        • Li T.
        • Liu Y.
        • Di B.
        • Wang M.
        • Shen J.
        • Zhang Y.
        • et al.
        Epidemiological investigation of an outbreak of pandemic influenza A (H1N1) 2009 in a boarding school: serological analysis of 1570 cases.
        J Clin Virol. 2011; 50: 235-239
        • Aho M.
        • Lyytikaïnen O.
        • Nyholm J.E.
        • Kuitunen T.
        • Rönkkö E.
        • Santanen R.
        • et al.
        Outbreak of 2009 pandemic influenza A(H1N1) in a Finnish garrison—a serological survey.
        Euro Surveill. 2010; 15 (pii=19709)
        • Papenburg J.
        • Baz M.
        • Hamelin M.È
        • Rhéaume C.
        • Carbonneau J.
        • Ouakki M.
        • et al.
        Household transmission of the 2009 pandemic A/H1N1 influenza virus: elevated laboratory-confirmed secondary attack rates and evidence of asymptomatic infections.
        Clin Infect Dis. 2010; 51: 1033-1041
        • Iwatsuki-Horimoto K.
        • Horimoto T.
        • Tamura D.
        • Kiso M.
        • Kawakami E.
        • Hatakeyama S.
        • et al.
        Sero-prevalence of pandemic (H1N1) 2009 influenza A virus among schoolchildren and their parents in Tokyo, Japan.
        Clin Vaccine Immunol. 2011; 18: 860-866

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