Safety and persistence of immunological response 6 months after intramuscular vaccination with an AS03-adjuvanted H1N1 2009 influenza vaccine

Abstract

This study evaluated the long-term persistence of immune response and safety of two doses of an A/California/7/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) in Japanese children (NCT01001169). Sixty healthy subjects aged 6 mo−17 y were enrolled (1:1) into two study groups to receive 21 d apart, two doses of 1.9µg haemagglutinin [HA]+AS03_B (5.93mg α-tocopherol) vaccine (6 mo−9 y) and 3.75µg HA+AS03_A (11.86mg α-tocopherol) vaccine (10–17 y), respectively. Immunogenicity data (by haemagglutination inhibition [HI] and microneutralisation assays) to six months after the first vaccine dose are reported here. It was observed that following Dose 2, the HI immune response against the vaccine homologous strain induced by the two different dosages of the AS03-adjuvanted vaccine met and exceeded the US and European regulatory guidance criteria for pandemic influenza vaccines (seroprotection rate[SPR]/seroconversion rate[SCR]: 100%/100%; geometric mean fold rise GMFR: 146.8/57.1). Further, the immune response persisted for at least six months after the first vaccine dose wherein these regulatory criteria were still met (SPR: 100%/100%; SCR: 96.4%/89.7%; GMFR: 25.3/23.5). The neutralising antibody response was comparable to the HI immune response at Day 42 (vaccine response rate [VRR]: 100%/100%) and at Day 182 (VRR: 96.4%/82.8%). Overall, both vaccine dosages had a clinically acceptable safety profile. Thus, two doses of a 1.9µg or 3.75µg HA AS03-adjuvanted H1N1 2009 pandemic influenza vaccine in children aged 6 mo−17 y induced strong immune responses against the vaccine homologous strain that persisted for at least six months after the first vaccine dose.

Keywords: :

• adjuvant
• H1N1
• influenza
• Japanese children
• pandemic

Disclosure of Potential Conflicts of Interest

Dr. A. Nagai was the principal investigator, Dr. A. Saitoh and Dr. T. Kato contributed as a supervisor in this study funded by GlaxoSmithKline. All participating institutions received compensation for study involvement. Drs. K. Tenjinbaru, D. Vaughn, F. Roman and P. Li are employees of GlaxoSmithKline Biologicals. D. Vaughn and F. Roman report ownership of stock options.

Financial disclosure

GlaxoSmithKline Biologicals was the funding source and was involved in all stages of the study conduct and analysis (ClinicalTrials.gov Identifier: NCT01001169). GlaxoSmithKline Biologicals also took in charge all costs associated with the development and the publishing of the present manuscript. All authors had full access to the data and the corresponding author had final responsibility to submit for publication.

Trademark statement

Arepanrix is a trade mark of the GlaxoSmithKline group of companies, Belgium.

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 and their parents, 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. We are grateful to all teams of GSK Biologicals for their contribution to this study, especially Shinobu Tamura, Hiroshi Tamura and Kazunori Yagi for clinical study management and site monitoring, and Roger Bernhard and Urban Lundberg from the clinical and serological laboratory teams, Dorothy Slavin (Clinical Safety Representative) and Edith Lepine 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. Wendy Van Doorslaer (XPE Pharma and Science, on behalf of GSK Biologicals) for editorial assistance and manuscript coordination.