Approximately 5%–20% of the US population contracts influenza infection annually with >200,000 hospitalizations and >35,000 deaths that occur mainly in older adults. We investigated determinants of immune response to influenza vaccine in relation to aging and concurrent HIV infection.Methods:
154 HIV infected (HIV+) virologically controlled persons on ART and 161 HIV uninfected (HIV−) grouped by age as young (<40 years), middle aged (40–59 years) and old (≥60 years) were given trivalent influenza vaccination. Serological responses to influenza vaccine antigens were correlated with cellular immune activation (IA), plasma markers of inflammation, and immune phenotype and function of peripheral leukocytes, including peripheral T follicular helper cells (pTffh).Results:
Absolute responders with >4 fold increase in titer to all the vaccine antigens were fewer in HIV+ (14%) than in HIV− (32%), lower in old compared to young, and inversely correlated with age for Ab to H1N1 and B antigen. Several immunologic markers were negative predictors of the vaccine response in HIV infection; these included higher levels of activated pTfh, monocytes expressing inflammatory marker CD11b, activated naive B cells, checkpoint inhibitor Tim3 on CD4 T cells and high plasma sCD25. Positive correlations were found with frequencies of bulk and antigen specific pTfh cells exhibiting high IL-21 and low IL-2 expression and lacking in inflammatory cytokines (TNFa, IL17) production. Although more deficiencies were evident in HIV+ old compared to other groups, the differences between HIV+ and HIV− for Ab responses and immunologic markers were maximal in young age.