A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

Abstract

Strategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged >= 65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 mu g of A/H1N1 and B, differing in A/H3N2 content (6 mu g or 12 mu g), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 mu g of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 mu g or 30 mu g) and/or in MF59 (R) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P < 0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P < 0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future

“…60,61,68 A study in the elderly compared fractional-dose ID delivery to the full IM dose of the unadjuvanted influenza vaccine (Fluvirin TM , Novartis), as well as to MF59-adjuvanted formulations with various antigen and adjuvant doses. 108 This study showed that the unadjuvanted ID approach yielded significantly higher immunogenicity at 6 mg HA/strain than unadjuvanted IM formulations at 15 mg or 30 mg HA/strain, in at least the A/ H1N1 strain, with non-inferior GMTs in the other strains. One study arm (12 mg HA/strain ID) was also higher with the A/ H3N2 strain compared to the unadjuvanted IM formulations.…”

MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life

“…The MF59 oil-in-water adjuvant (Adj) emulsion enhances influenza responses in the elderly and is licensed for immunization of individuals aged 65 years and older (9)(10)(11). In infants, a first trial evaluating MF59-adjuvanted versus nonadjuvanted monovalent A/H1N1 influenza vaccines between 6 and 36 months of age showed that MF59-adjuvanted formulations generated higher response rates with persistent seroprotection (12).…”

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy

“…In order to promote a regulatory response to the PIC19-A3 autoantigen we employed the CE-marked MJ600 device to target skin DCs whilst minimising the trauma of intradermal delivery and any ensuing cutaneous inflammation (Mutyambizi et al, 2009). The device has three hollow silicon MNs of 600μm length and has been used extensively in clinical studies to deliver a range of macromolecular formulations including insulin (Kochba et al, 2016), varicella zoster (Beals et al, 2016), polio (Anand et al, 2015;Troy et al, 2015) and seasonal and pandemic influenza vaccines (Della Cioppa et al, 2014;Hung et al, 2012a;Hung et al, 2012b;Levin et al, 2014;Levin et al, 2016;Van Damme et al, 2009). However, whilst there are a number of publications showing successful therapeutic readouts upon use of hollow MNs, there is a paucity of information related to the behaviour of injected materials in the local environment and how formulation or physicochemical drug properties influence distribution and retention in situ (Mansoor et al, 2015).…”