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Original Investigation
May 22, 2006

Safety of High Doses of Influenza Vaccine and Effect on Antibody Responses in Elderly Persons

Author Affiliations

Author Affiliations: Department of Molecular Virology and Microbiology and Department of Medicine, Baylor College of Medicine (Drs Keitel, Atmar, Cate, Greenberg, and Couch), and Veterans Affairs Medical Center (Dr Petersen), Houston, Tex; and sanofi pasteur, Swiftwater, Pa (Dr Ruben).

Arch Intern Med. 2006;166(10):1121-1127. doi:10.1001/archinte.166.10.1121

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 μg of hemagglutinin per strain (up to 180 μg 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-μg 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-μg dosage were 44% to 71% and 54% to 79%, respectively, higher than those in participants given the standard 15-μg dosage, and the 60-μg 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 high-dose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.