Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections

Amin Alirezaylavasani; Linda Gail Skeie; Ingrid Marie Egner; Adity Chopra; Tuva Børresdatter Dahl; Christian Prebensen; John Torgils Vaage; Bente Halvorsen; Fridtjof Lund-Johansen; Kristian Tonby; Dag Henrik Reikvam; Birgitte Stiksrud; Jan Cato Holter; Anne Ma Dyrhol-Riise; Ludvig A Munthe; Hassen Kared

doi:10.1038/s41541-024-00972-3

Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections

NPJ Vaccines. 2024 Oct 9;9(1):185. doi: 10.1038/s41541-024-00972-3.

Authors

Amin Alirezaylavasani^{1

2

3}, Linda Gail Skeie⁴, Ingrid Marie Egner^{1

2

3}, Adity Chopra^{1

3

5}, Tuva Børresdatter Dahl^{1

6

7}, Christian Prebensen^{4

7}, John Torgils Vaage^{1

7}, Bente Halvorsen^{6

7}, Fridtjof Lund-Johansen^{1

3

5}, Kristian Tonby^{4

7}, Dag Henrik Reikvam^{4

7}, Birgitte Stiksrud⁴, Jan Cato Holter^{7

8}, Anne Ma Dyrhol-Riise^{4

7}, Ludvig A Munthe^{9

10

11}, Hassen Kared^{12

13

14}

Affiliations

¹ Department of Immunology, Oslo University Hospital, Oslo, Norway.
² KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway.
³ Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.
⁴ Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁵ ImmunoLingo Convergence Center, University of Oslo, Oslo, Norway.
⁶ Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ Department of Microbiology, Oslo University Hospital, Oslo, Norway.
⁹ Department of Immunology, Oslo University Hospital, Oslo, Norway. [email protected].
¹⁰ KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway. [email protected].
¹¹ Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway. [email protected].
¹² Department of Immunology, Oslo University Hospital, Oslo, Norway. [email protected].
¹³ KG Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway. [email protected].
¹⁴ Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway. [email protected].

Abstract

The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm³). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.