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Background Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. Methods We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. Results We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. Conclusions Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. Clinical Trials Registration NCT03738241. [ABSTRACT FROM AUTHOR]

The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. 479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. Subjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis. MF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules. [ABSTRACT FROM AUTHOR]