MF59-adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Abstract

Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross-reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non-adjuvanted pre-pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre-pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross-reactive immunogenicity. MF59, the first oil-in-water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59-adjuvanted seasonal influenza vaccine (Fluad has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non-adjuvanted vaccines, and to provide cross-reactive immunity against divergent influenza strains. Similar results have been generated with a MF59-adjuvanted H5N1 pre-pandemic vaccine, which showed higher and broader immunogenicity compared with non-adjuvanted pre-pandemic vaccines.

Figure 1

Fluad to comparator post‐immunization GMT ratios and 95% confidence intervals for the B, A/H3N2 and A/H1N1 antigens after the first immunization •, second immunization and the third immunization ♦. These data are from a meta‐analysis that included all Fluad recipients with a low re‐immunization titre. The first immunization data are from 13 clinical trials (2102 Fluad recipients and 1498 comparator recipients), the second immunization data are from five clinical trials (463 Fluad recipients and 307 comparator recipients) and two clinical trials (149 Fluad recipients and 83 comparator recipients). Adapted from Podda A, 2001. ³⁹

Figure 2

Broad cross‐reactive immunity against heterologous H5N1 isolates. The figure shows the percentage of individuals who seroconverted following vaccination with an MF59‐adjuvanted (grey bars) or non‐adjuvanted (white bars) H5N3 vaccine. Participants received two doses of vaccine 21 days apart (post 2) and a booster vaccination 16 months later (post 3). Seroconversion was defined as a ≥ fourfold rise in pre‐vaccination antibody titre and was measured for the homologous (H5N3 Singapore strain) and mismatched (H5N1 Hong Kong 1997; H5N1 Hong Kong 2003; H5N1 Vietnam 2004; H5N1 Thailand 2004) strains. Additionally, some subjects who had received two doses of MF59‐adjuvanted H5N3 Singapore vaccine 6 years previously were re‐vaccinated with two doses 21 days apart of an MF59‐adjuvanted vaccine containing antigen derived from the H5N1 Vietnam strain. Seroconversion to the mismatched H5N1 Turkey strain was measured in these subjects after the first dose of H5N1 Vietnam (post 2) and after the second dose (post 3). Adapted from Stephenson I, et al. 2005, 2008. ⁵⁰ , ⁵⁴