Safety and Long-term Humoral Immune Response in Adults After Vaccination With an H1N1 2009 Pandemic Influenza Vaccine With or Without AS03 Adjuvant

• Published in: The Journal of infectious diseases 2012-03, Vol.205 (5), p.733-744
• Main Authors: Ferguson, Murdo, Risi, George, Davis, Matthew, Sheldon, Eric, Baron, Mira, Li, Ping, Madariaga, Miguel, Fries, Louis, Godeaux, Olivier, Vaughn, David
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Fatigue - etiology; Female; Fundamental and applied biological sciences. Psychology; Hemagglutination Inhibition Tests; Hemagglutinins - immunology; Humans; Immunity, Humoral; Infectious diseases; Influenza A Virus, H1N1 Subtype - immunology; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza Vaccines - standards; Influenza, Human - immunology; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Pain - etiology; Single-Blind Method; Time Factors; Tocopherols - administration & dosage; Tocopherols - adverse effects; Vaccination - methods; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir641

(See the editorial commentary by Neuzil, on pages 700-1.) Background.  In this study (NCT00985088) we evaluated different formulations of an H1N1 2009 pandemic influenza vaccine that deliver various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol-based oil-in-water adjuvant system). Methods.  A total of 1340 healthy subjects aged ≥18 years were randomized to receive 1 or 2 doses of an adjuvanted (3.75-μg HA/AS03A or 1.9-μg HA/AS03B) or nonadjuvanted vaccine formulation. Safety and immunogenicity (by hemagglutination-inhibition [HI] assay) after each dose and 6 months after dose 1 are reported here. Results.  A single dose of AS03A-adjuvanted 3.75-μg HA H1N1 2009 induced the strongest immune responses in subjects aged 18−64 years (seroprotection rate [SPR], 97.2%; seroconversion rate [SCR], 90.1%) as well as in subjects aged >64 years (SPR, 91.1%; SCR, 78.2%) 21 days after vaccination. Six months after dose 1, subjects who received 2 doses of either the adjuvanted formulation or 1 dose of the adjuvanted 3.75-μg HA formulation continued to meet all Center for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use criteria. All formulations had clinically acceptable safety profiles. Conclusion.  A single dose of the 3.75-μg HA AS03A-adjuvanted H1N1 2009 influenza vaccine was highly immunogenic in both age strata (18−64 and >64 years), inducing long-term persistence of the immune response until at least 6 months after dose 1.