tetano
Editor, Senior Moderator
Front Immunol
. 2024 Jan 26:14:1291048.
doi: 10.3389/fimmu.2023.1291048. eCollection 2023. 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
Tiza L Ng'uni[SUP] 1 [/SUP], Vernon Musale[SUP] 2 3 [/SUP], Thandeka Nkosi[SUP] 1 [/SUP], Jonathan Mandolo[SUP] 4 [/SUP], Memory Mvula[SUP] 4 [/SUP], Clive Michelo[SUP] 2 3 [/SUP], Farina Karim[SUP] 1 [/SUP], Mohomed Yunus S Moosa[SUP] 5 [/SUP], Khadija Khan[SUP] 1 [/SUP], Kondwani Charles Jambo[SUP] 4 6 [/SUP], Willem Hanekom[SUP] 1 7 [/SUP], Alex Sigal[SUP] 1 [/SUP], William Kilembe[SUP] 2 3 [/SUP], Zaza M Ndhlovu[SUP] 1 5 8 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: COVID-19; HCoV-NL63; HIV; SARS-CoV-2; T-cell response; antibody response.
. 2024 Jan 26:14:1291048.
doi: 10.3389/fimmu.2023.1291048. eCollection 2023. 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
Tiza L Ng'uni[SUP] 1 [/SUP], Vernon Musale[SUP] 2 3 [/SUP], Thandeka Nkosi[SUP] 1 [/SUP], Jonathan Mandolo[SUP] 4 [/SUP], Memory Mvula[SUP] 4 [/SUP], Clive Michelo[SUP] 2 3 [/SUP], Farina Karim[SUP] 1 [/SUP], Mohomed Yunus S Moosa[SUP] 5 [/SUP], Khadija Khan[SUP] 1 [/SUP], Kondwani Charles Jambo[SUP] 4 6 [/SUP], Willem Hanekom[SUP] 1 7 [/SUP], Alex Sigal[SUP] 1 [/SUP], William Kilembe[SUP] 2 3 [/SUP], Zaza M Ndhlovu[SUP] 1 5 8 [/SUP]
Affiliations
- PMID: 38343437
- PMCID: PMC10853422
- DOI: 10.3389/fimmu.2023.1291048
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: COVID-19; HCoV-NL63; HIV; SARS-CoV-2; T-cell response; antibody response.