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

作者：Hatz Christoph^*; von Sonnenburg Frank; Casula Daniela; Lattanzi Maria; Leroux Roels Geert

来源：Vaccine, 2012, 30(23): 3470-3477.

DOI：10.1016/j.vaccine.2012.03.017

• Influenza
• H1N1
• Vaccine
• Focetria
• MF59
• Booster

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. %26lt;br%26gt;Methods: This randomised trial enrolled 410 healthy adult (18-60 years) and 251 healthy elderly (%26gt;60 years) participants. Subjects received vaccine containing either 3.75 mu g or 7.5 mu g 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 15 mu g 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. %26lt;br%26gt;Results: All of the vaccine formulations investigated were highly immunogenic and well tolerated in both adult and elderly subjects. The 7.5 mu g 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 3.75 mu g and 7.5 mu g antigen were optimal for the adult and elderly populations, respectively. %26lt;br%26gt;Conclusions: These data demonstrate that one priming dose of MF59-adjuvanted A/H1N1 vaccine provided healthy adult (3.75 mu g or 7.5 mu g formulations) and healthy elderly (7.5 mu g 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. %26lt;br%26gt;Trial registration: www.clinicaltrials.gov (NCT00971906).

• 出版日期2012-5-14