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Ng’uni, Tiza L., Musale, Vernon, Nkosi, Thandeka, Mandolo, Jonathan, Mvula, Memory, Michelo, Clive, Karim, Farina, Moosa, Mohomed Yunus S., Khan, Khadija, Jambo, Kondwani 
ORCID: https://orcid.org/0000-0002-3195-2210, Hanekom, Willem, Sigal, Alex, Kilembe, William and Ndhlovu, Zaza M.
(2024)
'Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV'. Frontiers in Immunology, Vol 14, p. 1291048.
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Abstract
Background:
Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.
Methods:
We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses.
Results:
Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity.
Conclusion:
Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Cells and Genetics > QU 375 Cell physiology WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19 |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW) |
| Digital Object Identifer (DOI): | https://doi.org/10.3389/fimmu.2023.1291048 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 09 Feb 2024 09:05 |
| Last Modified: | 09 Feb 2024 09:06 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/24008 |
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