Cross-protective potential of a MF59-adjuvanted quadrivalent influenza vaccine in older adults

Abstract

A decline in humoral and cell-mediated immunity inevitably accompanies the ageing process. The weakened immunity in older people not only makes them more susceptible to natural influenza infections, but also prevents them from developing protective immunity to standard influenza vaccines. 1 McElhaney JE Influenza vaccine responses in older adults. Ageing Res Rev. 2011; 10: 379-388 Crossref PubMed Scopus (121) Google Scholar Besides immunosenescence, this reduced vaccine effectiveness can be associated with immunological responses to repeated vaccination. 2 Sullivan SG Price OH Regan AK Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations. Ther Adv Vaccines Immunother. 2019; 72515135519826481 Crossref Google Scholar Furthermore, the greatest effect of H3N2 influenza on the risk of hospitalisation relative to H1N1 and influenza B strains in the population aged 65 years or older 3 Thompson WW Shay DK Weintraub E et al. Influenza-associated hospitalizations in the United States. JAMA. 2004; 292: 1333-1340 Crossref PubMed Scopus (1733) Google Scholar suggests that a strong anamnestic response to the original infecting strain can be responsible for the disproportionate burden of H3N2 viruses, as this population was born during the era of circulation of H1N1 viruses. 4 Monto AS Malosh RE Petrie JG Martin ET The doctrine of original antigenic sin: separating good from evil. J Infect Dis. 2017; 215: 1782-1788 Crossref PubMed Scopus (68) Google Scholar This vulnerability of adults aged 65 or older underscores the need for effective preventive measures and ongoing efforts to improve the available influenza vaccines for this age group. To date, the most promising approach is to use so-called enhanced influenza vaccines, which either contain a higher dose of the antigen or are formulated with specific adjuvants. A successful example is the MF59 adjuvant that significantly enhanced the immunogenicity of inactivated influenza vaccines in older adults, 5 Gasparini R Pozzi T Montomoli E et al. Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects. Eur J Epidemiol. 2001; 17: 135-140 Crossref PubMed Scopus (97) Google Scholar for whom a switch to a quadrivalent formulation did not affect the overall immunogenicity and safety of the vaccine. 6 Essink B Fierro C Rosen J et al. Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults. Vaccine. 2020; 38: 242-250 Crossref PubMed Scopus (10) Google Scholar However, the question remained regarding to what extent this MF59-adjuvanted quadrivalent influenza vaccine (aQIV) can provide protection for older adults against the disease. Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy studyThe prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease. Full-Text PDF