Immunogenicity and safety of the MF59-adjuvanted seasonal influenza vaccine in non-elderly adults: a systematic review and meta-analysis

Background: In Europe age indication for the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) has been recently extended from ≥65 to ≥ 50 years old. Considering that the earliest approval of its trivalent formulation (aTIV) in Italy was for subjects aged ≥12 years, we aimed to systematically collect and appraise data on the immunogenicity, efficacy, and safety of aTIV/aQIV in non-elderly adults. Methods: A systematic literature review was conducted according to the available guidelines and studies were searched in MEDLINE, Biological Abstracts, Web of Science, Cochrane J library and clinical trial registries. Studies on absolute and relative immunogenicity, efficacy, effectiveness, and safety of a TIV/aQIV in non-elderly adults (<65 years) were potentially eligible. These endpoints were analyzed by virus (sub)types end vaccinee characteristics. Fixed- and random-effects meta-analyses were performed for data synthesis. Protocol registration: CR042024512472 Results: Twenty-four publications were identified analyzed. aTIV/aQIV was more immunogenic than non­ adjuvanted vaccines towards vaccine-like strains: the absolute differences in seroconversion rates were 8.8% (95% Cl: 3.7%. 14.0%), 13.1% (95% Cl: 6.7%. 19.6%) and 11.7% (95% Cl: 7.2%. 16.2%) for A(H1N1), A(H3N2) and B strains, respectively. This immunogenicity advantage was more pronounced in immunosuppressed adults. The corresponding differences in seroprotection rates were 3.8% (95% Cl: 1.0%, 6.6%), 8.6% (95% Cl: 4.0%, 13.2%) end 5.1% (95% Cl: 1.6%, 8.6%). Additionally. aTIV/aQIV was more immunogenic than non-adjuvanted counterparts towards heterologous A(H3N2) strains with a 10.7% (95% Cl: 3.2%. 18.2%) and 10.2% (95% Cl: 0.5%, 19.9%) difference in seroconversion and seroprotection rates respectively. Data on antibody persistence end efficacy were limited and inconclusive. From the safety standpoint, a TIV/aQIV was judged safe and well-tolerated, being most adverse events mild-to-moderate and self-limiting. However, compared with non-adjuvant vaccines the relative risks of local and systemic reactogenic events were 1.69 (95% Cl: 1.53. 1.86) and 1.35 (95% Cl: 1.01. 1.81), respectively. Serious adverse events were uncommon and no difference (risk ratio 1.02; 95% Cl: 0.64. 1.63) between aTIV/aQIV and non-adjuvanted formulations was found. Conclusions: In non-elderly adults. aTIV/aQIV is safe and may be more immunogenic than non-adjuvanted standard-dose vaccines.