Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial

Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials

“…Previously, the AS03 adjuvant system has been administered with H5N1 vaccines to a large number of adults (6,22,32) without raising any clinically observable safety concerns when monitored for up to 6 months following two-dose primary vaccination and also following a third (booster) dose administered at 6 months (33) or 14 months (23) In contrast to the experience with H5N1 where two doses of nonadjuvanted vaccine with HA levels above 30 g are required to fulfill licensure criteria in at least more than half of the vaccinees (3,22,36), the results presented here demonstrate that a single dose of A/H1N1/2009 vaccine containing either 15 g HA without adjuvant or 3.75 g HA with adjuvant is highly immunogenic in adults and sufficient to fulfill regulatory acceptance criteria for pandemic influenza vaccines. This suggests the existence of some level of immunological priming of the population for the A/H1N1/2009 strain, despite the fact that it is antigenically and genetically distinct from recently circulating influenza virus A H1N1 strains (13,15).…”

Adjuvanted influenza vaccines

“…In general adjuvants are well tolerated, though they may increase some local site symptoms, particularly injection site pain. Two Phase III studies of AS03 adjuvanted H5N1 have been performed covering 10,000 adults 84,85 . In these studies, the adjuvanted vaccine solicited local and general symptoms more frequently, including pain, fatigue, headache and myalgia.…”

Evaluation of Vaccines for H5N1 Influenza Virus in Ferrets Reveals the Potential for Protective Single-Shot Immunization

“…50% of subjects (25). Adjuvants, such as those based on aluminum salts (3) or the oil-inwater adjuvants MF59 (2,17,22) and ASO3 (13,21), have provided considerable antigen dose reduction, but in all clinical trials and preclinical animal evaluation to date, two doses of vaccine have been required to achieve what is considered to be adequate anti-HA antibody levels or protection, respectively (8,24).…”