A randomized clinical trial to identify the optimal antigen and MF59® adjuvant dose of a monovalent A/H1N1 pandemic influenza vaccine in healthy adult and elderly subjects

BACKGROUND: Vaccines against pandemic A/H1N1 influenza are required to protect the entire population. This dose range study aimed to identify priming antigen and adjuvant doses resulting in optimal levels of antibody-mediated protection after primary and one-year booster immunizations. METHODS: This randomised trial enrolled 410 healthy adult (18-60 years) and 251 healthy elderly (<60 years) participants. Subjects received vaccine containing either 3.75mug or 7.5mug antigen, adjuvanted with half the standard dose, or a standard dose of MF59((R)) (Novartis Vaccines) adjuvant, respectively. An additional adult cohort received non-adjuvanted vaccine containing 15mug antigen. Two doses of investigational vaccine were administered three weeks apart, followed by a single booster dose of adjuvanted seasonal influenza vaccine one year after priming. Immunogenicity was assessed by haemagglutination inhibition and microneutralization assays pre- and post-immunization, the safety profile of each vaccine was also evaluated. RESULTS: All of the vaccine formulations investigated were highly immunogenic and well tolerated in both adult and elderly subjects. The 7.5mug formulation induced the highest antibody titres after primary and booster immunizations, and resulted in better long-term antibody persistence, in both age groups. Assessment according to European licensure criteria for influenza vaccines concluded that single adjuvanted priming doses containing 3.75mug and 7.5mug antigen were optimal for the adult and elderly populations, respectively. CONCLUSIONS: These data demonstrate that one priming dose of MF59-adjuvanted A/H1N1 vaccine provided healthy adult (3.75mug or 7.5mug formulations) and healthy elderly (7.5mug formulation) individuals with adequate levels of seroprotection. Booster administration after two priming doses of either vaccine formulation resulted in the rapid development of seroprotective antibody titres. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00971906)