Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults

Hideyuki Ikematsu, Hideaki Nagai, Masahiro Kawashima, Yasunobu Kawakami, Kazuyoshi Tenjinbaru, Ping Li, Karl Walravens, Paul Gillard, François Roman, Hideyuki Ikematsu, Hideaki Nagai, Masahiro Kawashima, Yasunobu Kawakami, Kazuyoshi Tenjinbaru, Ping Li, Karl Walravens, Paul Gillard, François Roman

Abstract

Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.

Figures

Figure 1.
Figure 1.
Reverse cumulative curves for neutralising antibody responses 21 d after each of the two vaccine doses (Days 21 and 42) and six months after the first vaccine dose (Day 182) (ATP cohort for immunogenicity). ATP, according to protocol.

References

    1. Ministry of Health. Labour and Welfare (MHLW); Press Release (April 28, 2010). Available: Accessed July 15, 2011. Japanese.
    1. Ministry of Health. Labour and Welfare (MHLW); Press Release (February 05, 2010). Available: Accessed July 15, 2011. Japanese.
    1. Ministry of Health. Labour and Welfare (MHLW); Press Release (August 11, 2010). Available: Accessed July 15, 2011. Japanese.
    1. Kamigaki T, Oshitani H. Epidemiological characteristics and low case fatality rate of pandemic (H1N1) 2009 in Japan. PLoS Curr. 2009;1:RRN1139. doi: 10.1371/currents.RRN1139.
    1. Wada K, Nishiura H, Kawana A. An epidemiological analysis of severe cases of the influenza A (H1N1) 2009 virus infection in Japan. Influenza Other Respi Viruses. 2010;4:179–86. doi: 10.1111/j.1750-2659.2010.00143.x.
    1. Kawai N, Ikematsu H, Iwaki N, Satoh I, Kawashima T, Maeda T, et al. Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season. Clin Infect Dis. 2005;40:1309–16. doi: 10.1086/429241.
    1. Kawai N, Ikematsu H, Iwaki N, Maeda S, Satoh I, Hirotsu N, et al. A comparison of the effectiveness of oseltamivir for the treatment of influenza A and influenza B: a Japanese multicenter study of the 2003-2004 and 2004-2005 influenza seasons. Clin Infect Dis. 2006;43:439–44. doi: 10.1086/505868.
    1. Kawai N, Ikematsu H, Hirotsu N, Maeda T, Kawashima T, Tanaka O, et al. Clinical effectiveness of oseltamivir and zanamivir for treatment of influenza A virus subtype H1N1 with the H274Y mutation: a Japanese multicenter study of the 2007-2008 and 2008-2009 influenza seasons. Clin Infect Dis. 2009;49:1828–35. doi: 10.1086/648424.
    1. World Health Organization (WHO). Global Alert and Response (GAR). Pandemic influenza A (H1N1) 2009 virus vaccine – conclusions and recommendations from the October 2009 meeting of the immunization Strategic Advisory Group of Experts, December 04, 2009. Available at: Accessed July 15, 2011.
    1. World Health Organization (WHO). WHO recommendations on pandemic (H1N1) 2009 vaccines. Pandemic (H1N1) 2009: briefing note 2. Available at: Accessed July 15, 2011.
    1. Chu DWS, Hwang SJ, Lim FS, Oh HML, Thongcharoen P, Yang PC, et al. Immunogenicity and tolerability of an AS03A-adjuvanted prepandemic influenza vaccine. A phase III study in a large population of Asian adults. Vaccine. 2009;27:7428–35. doi: 10.1016/j.vaccine.2009.07.102.
    1. Nagai H, Ikematsu H, Tenjinbaru K, Maeda A, Dramé M, Roman FP. A phase II, open-label, multicentre study to evaluate the immunogenicity and safety of an adjuvanted prepandemic (H5N1) influenza vaccine in healthy Japanese adults. BMC Infect Dis. 2010;10:338. doi: 10.1186/1471-2334-10-338.
    1. Leroux-Roels I, Bernhard R, Gérard P, Dramé M, Hanon E, Leroux-Roels G. Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine. PLoS ONE 2008;3:e1665.
    1. Roman F, Vaman T, Gerlach B, Markendorf A, Gillard P, Devaster JM. Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03(A)- trial. adjuvant: Preliminary report of an observer-blind, randomized controlled trial. Vaccine. 2010;28:1740–5. doi: 10.1016/j.vaccine.2009.12.014.
    1. Carmona A, Oménaca F, Tejedor JC, Merino JM, Vaman T, Dieussaert I, et al. Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6–35 months. Vaccine. 2010;28:5837–44. doi: 10.1016/j.vaccine.2010.06.065.
    1. Ikematsu H, Nagai H, Kawashima M, Kawakami Y, Tenjinbaru K, Maeda A, et al. Immunogenicity and safety of a novel AS03A-adjuvanted H1N1 2009 pandemic influenza vaccine in adults in Japan. Hum Vaccin. 2010;6:888–93. doi: 10.4161/hv.6.11.12851.
    1. Nicholson KG, Abrams KR, Batham S, Clark TW, Hoschler K, Lim WS, et al. Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial. Lancet Infect Dis. 2011;11:91–101. doi: 10.1016/S1473-3099(10)70296-6.
    1. Madhun AS, Akselsen PE, Sjursen H, Pedersen G, Svindland S, Nøstbakken JK, et al. An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers. Vaccine. 2010;29:266–73. doi: 10.1016/j.vaccine.2010.10.038.
    1. World Health Organization (WHO) Influenza A(H1N1) 2009 virus: current situation and post-pandemic recommendations. Wkly Epidemiol Rec. 2011;86:61–65.
    1. Nicholson KG, Abrams K, Batham S, Clark T, Hoschler K, Lim W, et al. A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart. Health Technol Assess. 2010;14:193–334.
    1. Han T, Marasco WA . Structural basis of influenza virus neutralization. Ann NY Acad Sci. 2011 doi: 10.1111/j.1749-6632.2010.05829.x. Ahead of Print.
    1. Stephenson I, Heath A, Major D, Newman RW, Hoschler K, Junzi W, et al. Reproducibility of Serologic Assays for Influenza Virus A (H5N1) Emerg Infect Dis. 2009;15:1252–9. doi: 10.3201/eid1508.081754.
    1. World Health Organization (WHO). Global Alert and Response (GAR). Pandemic influenza A (H1N1) 2009 virus vaccine – conclusions and recommendations from the October 2009 meeting of the immunization Strategic Advisory Group of Experts, December 04, 2009. Available: Accessed July 15, 2011.
    1. Hehme NW, Künzel W, Petschke F, Gisela T, Carmen R, Christian Van H, et al. Ten years of experience with the trivalent split-influenza vaccine, Fluarix™. Clin Drug Investig. 2002;22:751–69. doi: 10.2165/00044011-200222110-00004.
    1. Baras B, de Waal L, Stittelaar KJ, Jacob V, Giannini S, Kroeze EJ, et al. Pandemic H1N1 vaccine requires the use of an adjuvant to protect against challenge in naïve ferrets. Vaccine. 2011;29:2120–6. doi: 10.1016/j.vaccine.2010.12.125.
    1. Reed LT, Muench H. A simple method of calculating fifty percent end point. Am J Hyg. 1938;27:493–8.
    1. European Committee for Proprietary Medicinal Products (CHMP). Guideline on influenza vaccine prepared from viruses with the potential to cause a pandemic and intended for use outside of the core dossier context (EMEA/CHMP/VWP/263499/2006). European Agency for the Evaluation of Medicinal Products, January 24, 2007.
    1. US Food and Drug Administration. (FDA) Guidance for Industry. Clinical data needed to support the licensure of pandemic influenza vaccines. US Food and Drug Administration May 2007. Available: Accessed July 15, 2011.

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