Vaccine-induced antibodies to heterologous influenza A H1N1 viruses: effects of aging and "original antigenic sin".

Prototype influenza A H1N1 viruses representing antigenically distinct Hsw1, H0, and H1 hemagglutinin variants that circulated during the early 1900s were used to measure cross-reactive serum hemagglutination inhibition antibodies elicited by contemporary inactivated virus vaccines in adults aged < 40 (young), 40-64 (middle-aged), or > or = 65 (elderly) years. Elevated titers of antibodies to Hsw1 and H0 antigens were present both before and after vaccination in higher proportions of middle-aged and elderly than young adults, whereas antibodies to more recent H1 antigens were prevalent in all age groups. Vaccine responses to heterologous H1N1 viruses were consistently reduced in frequency and magnitude with advancing age. Also, within each age group, antibody responses tended to diminish against progressively older heterologous antigens. These results confirm previous seroepidemiological surveys but suggest that preferential orientation of secondary antibodies toward priming epitopes ("original antigenic sin") is not responsible for the age-related impairment of antibody responses to influenza vaccine.