background and Aim: Influenza A/H3N2 infection emerged in 1968, causing a pandemic, and has subsequently undergone considerable antigenic and genetic variation. A/H3N2 strains have been associated with more severe epidemics than the other currently circulating influenza viruses (A/H1N1 and B), especially in vulnerable populations, such as the elderly with underlying medical conditions. MF59™ adjuvant has been shown to enhance immunogenicity of subunit influenza vaccine for both homologous and heterologous influenza strains. Immunity against heterologous strains is of particular medical significance during influenza epidemics when mismatches between vaccine strains and circulating influenza viruses occur. This study aimed to confirm if the presence of MF59™ in the vaccine formulation could improve immune responses against a heterovariant A/ H3N2 strain in elderly subjects with chronic conditions. methods: In a randomized, double-blind trial, elderly nursing home residents (≥65 years of age) in North-east Italy received either an MF59™ adjuvanted influenza vaccine (Sub/MF5 9 ; FLUAD®, Novartis Vaccines) , a split vaccine (Split; Mutagrip®, Pasteur Merieux MSD), or a virosomal vaccine (SVV; Inflexal-V®, Swiss Serum and Vaccine Institute) during the winter season of 1998/9 9 ; the majority of subjects had at least one underlying chronic disease, including a heart or lung condition or diabetes mellitus. Study vaccines contained the strains recommended by the WHO for 1998/99 Northern Hemisphere formulation (A/H3N2/Sydney/5/9 7 ; A/H1N1/ Beijing/262/95 and B/ Beijing/184/93). Blood samples were obtained pre-vaccination and at 4 weeks post-vaccination. Hemagglutination inhibition (HI) titres were measured against the A/H3N2 influenza antigen recommended for the 2006/07 vaccine formulation: A/H3N2/ Wisconsin/67/2005. Pre- and post-vaccination geometric mean antibody titres (GMTs), the post-vaccination mean-fold increase in HI antibodies (MFI), the number of subjects with protective HI titers (≥40), and the number of subjects with a four-fold increase in post-vaccination titers were calculated. Sera from 199 subjects were available for analysis (Sub/MF59: n=7 2 ; Split: n=8 8 ; SVV: n=39). More than 80% of subjects in each vaccination group were over 75 years of age. The Split group included more healthy subjects compared with the Sub/MF59 and SVV groups (39.8%, 12.5% and 20.5%, respectively). There were no male subjects in the SVV group (vs. 6.9% in the Sub/MF59 and 27.3% in the Split group). results: No statistically significant differences in baseline GMTs were observed between vaccine groups. Post-vaccination HI antibody titres against the heterovariant A/H3N2 strain were significantly higher (p=0.02) in the Sub/MF59 group, compared with SVV and Split groups. Compared with Split and SVV vaccines, MF59™ adjuvanted vaccine resulted in higher MFI (2.0, 2.0 and 3.1, respectively), and significantly greater proportions of subjects with at least a fourfold increase in antibody titers (27.3%, 23.1% and 41.7%, respectively, p=0.05). Seroprotective antibody levels were achieved by more vaccinees in the MF59™ adjuvanted and split vaccine groups (79.2% and 78.4%, respectively) than in the virosomal group (56.4%). Conclusion: MF59™ adjuvanted influenza vaccine induced higher HI antibody levels against a heterovariant A/H3N2 strain in this population of elderly people with chronic diseases, compared with conventional split and virosomal vaccines. These results confirm superior cross-reactive immunogenicity of MF59™ adjuvanted influenza vaccines. Since A/H3N2 influenza viruses are epidemiologically highly relevant for the elderly population, the broader immunogenicity conferred by FLUAD® could be of particular clinical benefit in seasons where an antigenic mismatch occurs

MF59®-adjuvanted influenza vaccine (Fluad®) in the elderly: greater immunogenicity against a heterovariant A/H3N2 strain, compared with split and virosomal vaccines

BALDO, VINCENZO;BALDOVIN, TATJANA;TRIVELLO, RENZO
2008

Abstract

background and Aim: Influenza A/H3N2 infection emerged in 1968, causing a pandemic, and has subsequently undergone considerable antigenic and genetic variation. A/H3N2 strains have been associated with more severe epidemics than the other currently circulating influenza viruses (A/H1N1 and B), especially in vulnerable populations, such as the elderly with underlying medical conditions. MF59™ adjuvant has been shown to enhance immunogenicity of subunit influenza vaccine for both homologous and heterologous influenza strains. Immunity against heterologous strains is of particular medical significance during influenza epidemics when mismatches between vaccine strains and circulating influenza viruses occur. This study aimed to confirm if the presence of MF59™ in the vaccine formulation could improve immune responses against a heterovariant A/ H3N2 strain in elderly subjects with chronic conditions. methods: In a randomized, double-blind trial, elderly nursing home residents (≥65 years of age) in North-east Italy received either an MF59™ adjuvanted influenza vaccine (Sub/MF5 9 ; FLUAD®, Novartis Vaccines) , a split vaccine (Split; Mutagrip®, Pasteur Merieux MSD), or a virosomal vaccine (SVV; Inflexal-V®, Swiss Serum and Vaccine Institute) during the winter season of 1998/9 9 ; the majority of subjects had at least one underlying chronic disease, including a heart or lung condition or diabetes mellitus. Study vaccines contained the strains recommended by the WHO for 1998/99 Northern Hemisphere formulation (A/H3N2/Sydney/5/9 7 ; A/H1N1/ Beijing/262/95 and B/ Beijing/184/93). Blood samples were obtained pre-vaccination and at 4 weeks post-vaccination. Hemagglutination inhibition (HI) titres were measured against the A/H3N2 influenza antigen recommended for the 2006/07 vaccine formulation: A/H3N2/ Wisconsin/67/2005. Pre- and post-vaccination geometric mean antibody titres (GMTs), the post-vaccination mean-fold increase in HI antibodies (MFI), the number of subjects with protective HI titers (≥40), and the number of subjects with a four-fold increase in post-vaccination titers were calculated. Sera from 199 subjects were available for analysis (Sub/MF59: n=7 2 ; Split: n=8 8 ; SVV: n=39). More than 80% of subjects in each vaccination group were over 75 years of age. The Split group included more healthy subjects compared with the Sub/MF59 and SVV groups (39.8%, 12.5% and 20.5%, respectively). There were no male subjects in the SVV group (vs. 6.9% in the Sub/MF59 and 27.3% in the Split group). results: No statistically significant differences in baseline GMTs were observed between vaccine groups. Post-vaccination HI antibody titres against the heterovariant A/H3N2 strain were significantly higher (p=0.02) in the Sub/MF59 group, compared with SVV and Split groups. Compared with Split and SVV vaccines, MF59™ adjuvanted vaccine resulted in higher MFI (2.0, 2.0 and 3.1, respectively), and significantly greater proportions of subjects with at least a fourfold increase in antibody titers (27.3%, 23.1% and 41.7%, respectively, p=0.05). Seroprotective antibody levels were achieved by more vaccinees in the MF59™ adjuvanted and split vaccine groups (79.2% and 78.4%, respectively) than in the virosomal group (56.4%). Conclusion: MF59™ adjuvanted influenza vaccine induced higher HI antibody levels against a heterovariant A/H3N2 strain in this population of elderly people with chronic diseases, compared with conventional split and virosomal vaccines. These results confirm superior cross-reactive immunogenicity of MF59™ adjuvanted influenza vaccines. Since A/H3N2 influenza viruses are epidemiologically highly relevant for the elderly population, the broader immunogenicity conferred by FLUAD® could be of particular clinical benefit in seasons where an antigenic mismatch occurs
2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2436612
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