Dose sparing and lack of dose response relationship with an influenza vaccine in adult and elderly patients - a randomized, double-blind clinical trial

Abstract

AIMS: The currently licensed seasonal trivalent influenza vaccines contain 15 micrograms of hemagglutinin per strain for adult, and up to 60 micrograms for elderly patients. However, due to recent shortages, dose sparing to increase production capacity would be highly desirable. In the present study, we attempted to find a dose-response relationship for immunogenicity and thus, the optimal dose for seasonal influenza vaccines in adult and elderly patients. METHODS: A total of 256 subjects, including adult (ages 18-60 years) and elderly (age over 60 years) were enrolled. Subjects were randomly assigned in a 1:1:1:1 ratio to receive a whole virion, aluminium adjuvanted trivalent influenza vaccine containing 3.5, 6, 9 or 15 micrograms of hemagglutinin of seasonal A/H1N1, A/H3N2 and B influenza antigens manufactured by Omninvest Ltd., Hungary. Serum antibody titres against the vaccine virus strains were measured by hemagglutination inhibition. RESULTS: All vaccines were well tolerated. All four vaccines fulfilled all three immunogenicity licensing criteria as determined in CPMP/BWP/214/96 guideline for all three virus strains and both age groups. The 3.5 microgram vaccine showed 28% less seroconversion compared to the 15 microgram dose in terms of influenza AH3N2 in the adult group (95% CI: -51; -3, p < 0.05). All other doses showed no significant difference in immunogenicity compared to the licensed vaccine with 15 micrograms. CONCLUSIONS: Our data suggest that significant dose sparing is possible with the use of whole virion vaccines and aluminium adjuvants, without compromising safety. This can have significant economic and public health impacts.