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.

Safety, immunogenicity, and tolerability of three influenza vaccines in older adults

“…This study is notable for directly comparing 3 influenza vaccines in older adults, whereas previous studies typically compared a new vaccine to TIV 8,10,11,18 or new vaccines to each other. 13 This study benefitted from a high degree of similarity among the study groups, effectively controlling for a range of potential influences on responses to vaccination including age, 19 sex, prior influenza vaccination, 15,16 frailty, 20 chronic health conditions, obesity, 21 moderate exercise 22 and probiotic use.…”

“…Group size of 300 also provided over 90% power to detect GMT ratios in the range of 1.25 to 1.5, as in previous comparisons of ADV and different TIVs. 8,18 The selected group size also applied satisfactorily to comparisons of IDV and TIV, as published response rate differences were similar to those above. 9,10 Group sizes of 300 provided sufficient power to recognize differences in rates of adverse events of 12% or more, with 80% probability.…”

“…Based on reported seroprotection rate differences in comparisons of ADV and a different TIV, 8,18 we determined that groups of 300 would allow detection of rate differences ≥ 15% with at least 90% probability using one-sided tests, across a range of potential rate pairs with 3 viral strains. Group size of 300 also provided over 90% power to detect GMT ratios in the range of 1.25 to 1.5, as in previous comparisons of ADV and different TIVs.…”

Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review

“…APCs acquire an increased ability to capture, transport and process co-administered antigens from the peripheral tissues to local lymph nodes and consequently, stimulate an effective adaptive memory immune response specific to the vaccine. [13][14][15] Intanza 15mcg Ò (Sanofi Pasteur MSD SNC, France) is a split trivalent non-adjuvanted influenza vaccine administered intradermally (ID) which uses an innovative microinjection system (Soluvia, Becton Dickinson, USA) and has been available in Italy since the Winter season 2010-2011. The manufacturing processing is based on that used for the intramuscular seasonal vaccine although a lower volume is used for intradermal vaccine (15 mg HA/strain per 0.1 ml instead of 0.5 ml).…”

Pre-pandemic and pandemic influenza vaccines

“…In healthy adults, paediatric and elderly populations, two injections using vaccines containing these adjuvants have been required to achieve compliance with the European Committee for Medicinal Products guideline with respect to antibody response (reviewed in ref. [51][52][53].…”