Immunogenicity Profile of a 3.75-μg Hemagglutinin Pandemic rH5N1 Split Virion AS03A-Adjuvanted Vaccine in Elderly Persons: A Randomized Trial

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of ASO3(A)-adjuvanted H5N1 pandemic vaccine (3.75 mu g hemagglutinin of A/Vietnam/1194/ 2004-like strain) compared with a double dose in an elderly population. Methods. This phase 2, open-label study (NCT003972 15; http://www.clinicaltrials.gov) randomized participants (age, >= 61 years) to receive, on days 0 and 21: (1) a single dose of ASO3(A)-adjuvanted vaccine (n = 152), (2) a single dose of nonadjuvanted vaccine (n = 54), (3) a double dose of ASO3(A)-adjuvanted vaccine (n = 145), or (4) a double dose of nonadjuvanted vaccine (n = 44). The primary end point was hemagglutination inhibition (HI) and neutralizing antibody response against vaccine antigen (according-to-protocol cohort). Results. Day 42 geometric mean titers for HI antibodies were 126.8 and 237.3 for single and double doses of the ASO3(A)-adjuvanted vaccine, respectively. Corresponding values for neutralizing antibodies were 447.3 and 595.8. Although the immune response was higher with the double dose, European Committee for Human Medicinal Products criteria for seroconversion and seroprotection rates were achieved in both ASO3(A)-adjuvanted groups. Antigen-specific CD4 T cell responses were elicited. Immune response persistence at 6 months was high. Immune response in the non-adjuvanted groups was considerably less. Conclusions. The ASO3(A)-adjuvanted H5Ni vaccine can be administered elderly persons at the same dose and schedule as in younger adults.