Comparative Study of Immunogenicity of Split, Intradermal and MF59-adjuvanted Influenza Vaccines in Elderly Institutionalized Subjects

Abstract The reduced immunogenicity and effectiveness of influenza vaccines in subjects presenting high risk of influenza-related complications, hospitalization and death, led the innovative drive to search for new strategies to implement the immune response elicited by influenza vaccines including addition of adjuvants, and use of alternative routes of antigen delivery.In this study we evaluated and compared the immune antibody response induced in 252 elderly volunteers living in nursing homes after immunization with three different 2012-2013 seasonal trivalent inactivated influenza vaccines: a conventional split vaccine (n=26), and two potentiated vaccines (a subunit vaccine adjuvanted with MF59 (n=137) or a split vaccine administered intradermally (n=89)), specially licensed for elderly people. Haemagglutination inhibiting (HI) antibody titers were assessed in blood samples collected before and one month after vaccination.The results were evaluated as increase in HI titers found comparing pre- and post-vaccination sera and according to the Committee for Medicinal Products for Human Use (CHMP) criteria for approval of influenza vaccines in the elderly. Significant antibody increases and fulfillment of all the three CHMP requirements were observed against A/H3N2 and B antigens following immunization with the two potentiated vaccines. After immunization with conventional vaccine responses were lower against A/H3N2 and equivalent against the B antigen. The two potentiated vaccines induced significant antibody increases against A/H1N1 antigen, however, only one of the CHMP criteria was reached. The HI antibody increases after conventional vaccine were significant only for the geometric mean titer and none of the CHMP criteria was fulfilled. The antibody responses induced by the two potentiated vaccines against the three vaccine antigens wereequivalent although post-vaccination titers against the B antigen tended to be higher in subjects vaccinated with intradermal vaccine than in individuals receiving MF59-adjuvanted vaccine. In conclusion the use of MF59 adjuvant and intradermal vaccination appear to be appropriate strategies to address the challenge of declining immune response in the elderly after influenza vaccination