Evaluation of immune response following one dose of an AS03_A-adjuvanted H1N1 2009 pandemic influenza vaccine in Japanese adults 65 years of age or older

Abstract

Objective: This study assessed the immunogenicity, long-term persistence of immune response and safety of a single dose of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (α-tocopherol and squalene based oil-in-water emulsion Adjuvant System) in subjects ≥ 65 y of age (NCT01114620).

Results: At Day 21, the HI immune response met all three European guidance criteria [seroconversion rate (SCR): 60.0%; seroprotection rate (SPR): 64.0%; geometric mean fold rise (GMFR): 10.2] and the US guidance criterion for SCR. At month 6, the HI immune response against the A/California/07/2009 H1N1 strain persisted but at levels lower than that observed at Day 21 (SCR: 38.8%; SPR: 42.9%; HI antibody geometric mean titer: 27.6); the European regulatory guidance criteria for SCR and GMFR were still met. Overall, the vaccine was well-tolerated.

Conclusion

A single dose of the 3.75µg HA AS03-adjuvanted H1N1 2009 pandemic vaccine induced immune responses against the vaccine strain that met the European regulatory guidance criteria at day 21 in the elderly Japanese population; the immune response persisted at lower levels at month 6. No safety concerns were identified. These results suggest that two vaccine doses might be useful for the elderly population to improve antibody induction and persistence.

Methods: In this open-label, single group study, 50 subjects received one dose of the 3.75 µg hemagglutinin (HA) AS03-adjuvanted H1N1 2009 vaccine. Immunogenicity assessments were made before vaccination, 21 days and six months after vaccination using hemagglutination inhibition (HI) and microneutralization assays. Immunogenicity end points were based on US and European regulatory criteria.

Keywords: :

• AS03
• H1N1
• Japan
• adjuvant
• adults
• elderly
• influenza
• pandemic

Disclosure of Potential Conflicts of Interest

Dr H.I. was the principal investigator. All participating institutions received compensation for study involvement. Drs K.T., A.M., D.V. and P.L. are employees of GlaxoSmithKline Biologicals.

Financial Disclosure Statement

GlaxoSmithKline Biologicals was the funding source and was involved in all stages of the study conduct and analysis (ClinicalTrials.gov Identifier: NCT01114620). GlaxoSmithKline Biologicals also took in charge all costs associated with the development and the publishing of the present manuscript.

Trademark Statement

Arepanrix is a trademark of the GlaxoSmithKline group of companies.

Acknowledgments

All authors participated in the implementation of the study including substantial contributions to conception and design, the gathering of the data, or analysis and interpretation of the data. All authors were involved in the drafting of the article or revising it critically for important intellectual content, and final approval of the manuscript. We are grateful to the New York Medical College, New York for providing the vaccine virus reassortant and to the National Institute for Biological Standards and Control (NIBSC, UK) and Therapeutic Goods Administration (TGA) from the Australian Government for providing the reference standards. The authors are indebted to the participating study volunteers, clinicians, nurses and laboratory technicians at the study sites as well as to the sponsor’s project staff for their support and contributions throughout the study. In particular, we thank Yasunobu Kawakami. We are grateful to all teams of GSK Biologicals for their contribution to this study, especially Hiroshi Tamura, Shinobu Tamura, Yoko Nakagawa and Kenji Ishizuka for clinical study management and site monitoring, Veronique Grosjean and Ophélie Gascard for database management, Roger Bernhard and Urban Lundberg from the clinical and serological laboratory teams, Dorothy Slavin (Clinical Safety Representative) and Kimberly Cerenze for project management. Finally the authors thank Dr. Karl Walravens for critical review of the manuscript, Avishek Pal (GSK Biologicals) for providing medical writing services and Dr. Geraldine Drevon (GSK Biologicals) for editorial assistance and manuscript coordination. All authors had full access to the data and the corresponding author had final responsibility to submit for publication.