Antibody response against unchanged influenza vaccine components in elderly people vaccinated in consecutive years

Background: Annual influenza vaccination is recommended for high risk groups because of the frequent mutations of influenza viruses and the rapid decline of vaccine induced antibody titers. Field studies demonstrated that annually repeated vaccination is efficacious in reducing morbidity and mortality. Serologic studies, however, showed divergent results on the induction of protective antibodies after annually repeated vaccination and a decline of immune antibody response was observed especially in the years when vaccine strains did not change. To further address the effect of annual vaccination we studied the haemagglutination inhibiting (HI) antibody response of elderly institutionalized yearly vaccinated volunteers against vaccine antigens which for sequential years were not changed over 16 consecutive seasons, from 1998/99 to 2013/14. Materials and Methods: The volunteers enrolled were elderly institutionalized people aged >60 years, annually vaccinated for influenza. HI titers were determined in serum samples taken before and 1 month after vaccination by a standard microtiter method. Differences in HI titers were analyzed by Student’s t-test for continuous statistics, and by chi-square test for qualitative statistics. Results: HI antibody responses were studied in 6 cohorts of volunteers against vaccine antigens not changed in consecutive years. Responses against A/H1N1 antigens were examined in 16 subjects against A/New Caledonia/20/99 for 7 consecutive years (from 1998/99 to 2006/07), and in 36 subjects against A/California/7/09 for 4 years (from 2010/11 to 2013/14). Against A/H3N2 antigens 38 subjects were examined against A/Moscow/10/99 for 4 years (from 2000/01 to 2003/04). Responses for B antigens were studied in 51 subjects against B/Beijing/184/93 for 3 years (from 1998/99 to 2000/01), and in 41 subjects against B/Brisbane/60/08 for 3 years (from 2009/10 to 2011/12). The pre-vaccination HI antibody titers found after the first year of administration tended to be higher for A/H3N2 and B/Brisbane antigens and similar or slightly lower for the two A/H1N1 and for B/Beijing antigens. The vaccine-induced HI antibody response against the different antigens studied was substantially positive, comparing pre- and post-vaccination sera, the increases in HI antibody titers resulted in most instances statistically significant. The post-vaccination values observed in the sequential years were in general similar for B/Beijing, slightly lower for the two A/H1N1 antigens and higher for B/Brisbane and A/H3N2 strains. The requirements of the European Commission were satisfied more frequently in the early years of administration with the exception for the B antigens. Conclusions: The results obtained confirm the complexity of antibody induction in sequential annual influenza vaccination. Although we cannot exclude other mechanisms, our data seem to support the possibility of an impairment of antibody response against unaltered influenza A/H1N1 antigens that have circulated for prolonged periods whereas the responses against the A/H3N2 and B vaccine strains, more frequently changed, tended to be similar or higher.