PhD candidate University of Miami Miller School of Medicine, United States
Disclosure(s):
Sheldon Davis: No financial relationships to disclose
Introduction/Rationale: We have previously noted that flu vaccine responses decline with aging and further impaired in people with HIV (PWH), linked to chronic inflammation and impaired peripheral T follicular helper cell (pTfh) function. This study evaluated young (Y) and old (O) virally suppressed people with HIV (PWH) and people without HIV (PWoH) to determine whether high-dose (HD) vaccination could overcome pTfh defects.
Methods: Participants (mean age, n) included YPWH (33, n=10), OPWH (65, n=19), YPWoH (31, n=10), and OPWoH (65, n=19), who received a standard-dose (SD) influenza vaccine in one season followed by HD the next. PBMC at D0 and D14 were stimulated with A/H1N1 for 12h and stained (surface/ICS) to identify Activation Induced Markers (AIM) CD40L and CD69 in pTfh (CD45RO⁺CXCR5⁺ PD-1hi)) CD4+ T cells and intracellular cytokines by high-dimensional flow cytometry. Serum A/H1N1 and whole-vaccine (WV) HAI titers were measured at D0 and D28.
Results: With SD, A/H1N1 D28/D0 titer fold change (FC) was higher in PWoH than PWH. H1N1-induced AIM⁺ pTfh frequencies did not differ across groups at D0 or D14 post-SD vaccine. In AIM⁺ pTfh cells at D14, intracellular IL-21 was similar between groups, but IL-2 and TNF-α (deleterious for Ab production) were higher in O vs Y participants. In OPWH, TNF-α at D14 negatively correlated with WV titer FC (r=-0.78, p=0.04). In YPWoH, ICOS expression increased and the Th2 marker CCR6 was reduced in AIM+ pTfh cells from D0 to D14. In YPWH, HD increased pTfh frequencies at D14 verse SD and correlated with WV (r=0.64, p=0.046) and H1N1 titer FC (r=0.71, p=0.002). HD vaccination lowered IFN-γ and IL-2 in AIM+ pTfh cells versus SD among Y participants, while O participants increased ICOS expression that correlated with WV (r=0.74, p=0.002) and H1N1 titer FC (r=0.54, p=0.036) in OPWH.
Conclusion: HD vaccination increased AIM⁺ pTfh frequency, enhanced ICOS expression and reduced pro-inflammatory cytokine production in pTfh with improved vaccine responses in aging individuals and PWH.
