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

AIMS The currently licensed seasonal trivalent influenza vaccines contain 15 mu g haemagglutinin per strain for adult, and up to 60 mu g 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 (aged 18-60 years) and elderly (aged over 60 years) individuals, 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 mu g haemagglutinin 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 haemagglutination inhibition. RESULT All vaccines were well tolerated. All four vaccines fulfilled all three immunogenicity licensing criteria, as determined by the European Committee for Proprietary Medicinal Products (CPMP)/Biotechnology Working Party (BWP)/214/96 guideline for all three virus strains and both age groups. The 3.5 mu g vaccine showed 28% less seroconversion compared to the 15 mu g dose in terms of influenza AH3N2 in the adult group (95% confidence interval -51, -3; P < 0.05). All other doses showed no significant difference in immunogenicity compared with the licensed vaccine containing 15 mu g haemagglutinin. CONCLUSIONS Our data suggested that significant dose sparing is possible with the use of whole-virion vaccines and aluminium adjuvants, without compromising safety. This could have significant economic and public health impacts.