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IL-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 (PLWH)
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  • Samir Kumar-Singh,
  • Akshita Gupta,
  • Elda Righi,
  • Angelina Konnova,
  • Concetta Sciammarella,
  • Gianluca Spiteri,
  • Vincent Van Averbeke,
  • Matilda Berkell,
  • * Hotterbeekx,
  • Assunta Sartor,
  • Massimo Mirandola,
  • Surbhi Malhotra-Kumar,
  • Anna Maria Azzini,
  • Diletta Pezzani,
  • Maria Grazia Lourdes Monaco,
  • Guido Van Ham,
  • Stefano Porru,
  • Evelina Tacconelli
Samir Kumar-Singh
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie

Corresponding Author:samir.kumarsingh@uantwerpen.be

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Akshita Gupta
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie
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Elda Righi
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Angelina Konnova
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie
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Concetta Sciammarella
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Gianluca Spiteri
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Vincent Van Averbeke
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie
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Matilda Berkell
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie
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* Hotterbeekx
Universiteit Antwerpen Laboratorium voor Celbiologie en Histologie
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Assunta Sartor
Universita degli Studi di Udine Dipartimento di Scienze giuridiche
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Massimo Mirandola
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Surbhi Malhotra-Kumar
Universiteit Antwerpen Laboratory for Microbiology Parasitology and Hygiene
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Anna Maria Azzini
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Diletta Pezzani
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Maria Grazia Lourdes Monaco
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Guido Van Ham
Universiteit Antwerpen Collaborative Antwerp Psychiatric Research Institute
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Stefano Porru
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Evelina Tacconelli
Universita degli Studi di Verona Dipartimento di Diagnostica e Sanita Pubblica
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Abstract

People living with HIV (PLWH) despite having appreciable depletion of CD4 + T-cell show a good SARS-CoV-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 + counts as PLWH-high (CD4 ≥500 cells/μL) and PLWH-low (<500 cells/μL). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), and 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 to age and vaccination-matched HIV-negative controls at T3. The IgG titers were also protective showing a good correlation with ACE2-neutralizations (R=0.628, P=0.005). While no difference at T3 was observed between PLWH and controls in activated CD4 +CD154 + and CD4 + memory T-cells, spike-specific CD4 + polyfunctional cytokine expression analysis showed that PLWH preferentially express IL-2 (P<0.001) and controls, IFN-γ (P=0.017). CD4 + T-cell counts negatively correlated with IL-2-expressing CD4 + T-cells including CD4 + memory T-cells (Spearman ρ: ­ -0.85 and -0.80, respectively; P<0.001). Our results suggest that the durable serological and CD4 + T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4 + T-cell activation that likely compensates for CD4 + T-cell depletion in PLWH.
04 Mar 2024Submitted to Journal of Medical Virology
04 Mar 2024Review(s) Completed, Editorial Evaluation Pending
10 Jun 2024Editorial Decision: Revise Major
06 Jul 2024Reviewer(s) Assigned
07 Jul 2024Review(s) Completed, Editorial Evaluation Pending
09 Jul 2024Editorial Decision: Accept