Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons

Background: Immune responses after influenza immunization are reduced in elderly individuals, the group at greatest risk for complications and death after influenza. Improved vaccines are needed to address this problem. Methods: Ambulatory individuals 65 years and older (N = 202) were assigned randomly to receive a single intramuscular injection of the 2001 - 2002 formulation of trivalent inactivated influenza vaccine containing 15, 30, or 60 mu g of hemagglutinin per strain (up to 180 mu g total per dose) or placebo. Clinical and serologic responses were assessed during the month after immunization. Results: Increasing dosages of vaccine elicited significantly higher serum antibody levels, frequencies of antibody responses, and putative protective titers after vaccination. Mean serum hemagglutination inhibition antibody titers 1 month after immunization in groups given 0-, 15-, 30-, and 60-mu g dosages were 23, 37, 50, and 61 against influenza A/H1N1; 43, 86, 91, and 125 against influenza A/H3N2; and 10, 14, 18, and 24 against influenza B, respectively. Mean serum hemagglutination inhibition and neutralizing antibody levels against the 3 vaccine antigens in participants given the 60-mu g dosage were 44% to 71% and 54% to 79%, respectively, higher than those in participants given the standard 15-mu g dosage, and the 60-mu g dosage level nearly doubled the frequency of antibody responses in those whose preimmunization antibody titers were in the lower half of the antibody range. Dose-related increases in the occurrence of injection site reactions were observed (P <.001), but all dosages were well tolerated. Conclusion: The improved immunogenicity of highdose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.