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J Med Virol . Interleukin-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccinat

tetano

Editor, Senior Moderator
J Med Virol


. 2024 Aug;96(8):e29820.
doi: 10.1002/jmv.29820. Interleukin-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV

Akshita Gupta[SUP] 1 2 [/SUP], Elda Righi[SUP] 3 [/SUP], Angelina Konnova[SUP] 1 2 [/SUP], Concetta Sciammarella[SUP] 3 [/SUP], Gianluca Spiteri[SUP] 4 [/SUP], Vincent Van Averbeke[SUP] 1 [/SUP], Matilda Berkell[SUP] 1 2 [/SUP], An Hotterbeekx[SUP] 1 2 [/SUP], Assunta Sartor[SUP] 5 [/SUP], Massimo Mirandola[SUP] 3 6 [/SUP], Surbhi Malhotra-Kumar[SUP] 2 [/SUP], Anna Maria Azzini[SUP] 3 [/SUP], Diletta Pezzani[SUP] 3 [/SUP], Maria Grazia Lourdes Monaco[SUP] 4 [/SUP], Guido Vanham[SUP] 7 [/SUP], Stefano Porru[SUP] 4 [/SUP], Evelina Tacconelli[SUP] 3 [/SUP], Samir Kumar-Singh[SUP] 1 2 [/SUP]



Affiliations
Abstract

People living with HIV (PLWH) despite having an appreciable depletion of CD4[SUP]+[/SUP] T-cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4[SUP]+[/SUP] counts as PLWH-high (CD4 ≥ 500 cells/mm[SUP]3[/SUP]) and PLWH-low (<500 cells/mm[SUP]3[/SUP]). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different from age and vaccination-matched HIV-negative controls at T3. The immunoglobulin G titers were also protective showing a good correlation with angiotensin-converting enzyme 2-neutralizations (R = 0.628, p = 0.005). While surface and intracellular activation analysis showed no significant difference at T3 between PLWH and controls in activated CD4[SUP]+[/SUP]CD154[SUP]+[/SUP] and CD4[SUP]+[/SUP] memory T-cells, spike-specific CD4[SUP]+[/SUP] polyfunctional cytokine expression analysis showed that PLWH preferentially express interleukin (IL)-2 (p < 0.001) and controls, interferon-γ (p = 0.017). CD4[SUP]+[/SUP] T-cell counts negatively correlated with IL-2-expressing CD4[SUP]+[/SUP] T-cells including CD4[SUP]+[/SUP] memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; p < 0.001). Our results suggest that the durable serological and CD4[SUP]+[/SUP] T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4[SUP]+[/SUP] T-cell activation that likely compensates for CD4[SUP]+[/SUP] T-cell depletion in PLWH.

Keywords: COVID‐19; T cell; cytokine; people living with HIV; serology; vaccine.

 
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