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

Abstract

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004-like strain) compared with a double dose in an elderly population.Methods. This phase 2, open-label study (NCT00397215; http://www.clinicaltrials.gov) randomized participants (age, ≥61 years) to receive, on days 0 and 21: (1) a single dose of AS03A-adjuvanted vaccine (n = 152), (2) a single dose of nonadjuvanted vaccine (n = 54), (3) a double dose of AS03A-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 AS03A-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 AS03A-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 AS03A-adjuvanted H5N1 vaccine can be administered elderly persons at the same dose and schedule as in younger adults.

Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: A randomized controlled clinical trial

“…In one European study of adults ≥61 years, 38% of participants had anti-influenza A/Vietnam/1194/2004-like clade 1 strain HI antibody at baseline and 90% had MN antibody [17]. In our study, MN to A/Vietnam was high at baseline (Supplemental Fig.…”

“…Participants with an antibody titer of <1:28 were considered seronegative, and the reciprocal titer value assigned to a MN results below cut-off was one-half of the cut-off value, or 14. If the baseline titer was below cut-off and the post-vaccination reciprocal titer was ≥56, the participant was deemed to have had a MN vaccine response [17,18].…”

Matrix MTMadjuvanted virosomal H5N1 vaccine induces balanced Th1/Th2 CD4+T cell responses in man

“…This has also previously been shown for oil-in-water adjuvants in previous human studies of H5N1. 21,22,31 Similarly, both specific CD4+ T cells and Th1 and Th2 cytokines were increased after immunization with AS03 adjuvanted pandemic H1N1 vaccine. [32][33][34] We also evaluated cytokine production upon stimulation in vitro with heterologous H5 clades (Anhui, clade 2.3.4, and BHG, clade 2.2).…”

Influenza vaccination for older adults

“…The single dose schedule, produced a lower immune response than the double dose, but still was adequate to meet licensing requirements. 45 ( Table 1)…”