High-dose influenza vaccine augments serological and cellular immunity of older people with HIV.

BACKGROUNDHigh-dose influenza vaccine, containing 4 times more antigen than the standard dose, is recommended for people 65 years or older, but there is a knowledge gap surrounding its effect in people with HIV (PWH), who remain more vulnerable to serious influenza infections than people without HIV (PWoH) despite virological suppression. Our primary goal was to assess whether the high-dose vaccine improves antibody responses in PWH, especially older PWH.METHODSWe assessed antibody responses to sequential high- versus standard-dose influenza vaccination in PWH. Young (18-40 years) PWoH (n = 55) and PWH (n = 37) and older (≥60 years) PWoH (n = 72) and PWH (n = 67) received a standard-dose vaccine during the 2020-2024 seasons, and 123 participants (41 older PWH) received a high-dose vaccine the subsequent season. All PWH were virologically suppressed on antiretroviral therapy. HA inhibition (HAI) titer and HA-specific IgG were analyzed at 0 to 180 days after vaccination; T cell activation-induced responses were assessed by flow cytometry.RESULTSAll groups mounted significant HAI and IgG responses to all vaccine antigens at 28 days after standard- and high-dose vaccination. Responses to A/H1N1 were lower in magnitude and durability in older PWH compared with young PWoH after the standard dose and were not boosted with the high dose, whereas the high dose enhanced A/H3N2 and B/Victoria IgG, in addition to CD4+ T cell responses to all antigens, in older PWH.CONCLUSIONOur data demonstrate partial efficacy of a high-dose vaccine in augmenting antibody responses of older PWH while highlighting limitations in boosting A/H1N1-specific responses.TRIAL REGISTRATIONClinicalTrials.gov NCT04487041.FUNDINGNIH grant (5R01AG068110).