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.

COVID-19 HCoV-NL63 HIV SARS-CoV-2 T-cell response antibody response

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 08 09 2023
accepted: 18 12 2023
medline: 12 2 2024
pubmed: 12 2 2024
entrez: 12 2 2024
Statut: epublish

Résumé

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. 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. Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4 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.

Sections du résumé

Background UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4
Conclusion UNASSIGNED
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.

Identifiants

pubmed: 38343437
doi: 10.3389/fimmu.2023.1291048
pmc: PMC10853422
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1291048

Informations de copyright

Copyright © 2024 Ng’uni, Musale, Nkosi, Mandolo, Mvula, Michelo, Karim, Moosa, Khan, Jambo, Hanekom, Sigal, Kilembe and Ndhlovu.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Front Immunol. 2023 Feb 16;14:1108716
pubmed: 36875071
Sci Rep. 2021 Mar 18;11(1):6283
pubmed: 33737527
Cell. 2021 Apr 29;184(9):2384-2393.e12
pubmed: 33794143
Nat Commun. 2021 Oct 5;12(1):5839
pubmed: 34611163
Cell Rep Med. 2023 Jun 20;4(6):101088
pubmed: 37295422
Chin Med J (Engl). 2020 May 5;133(9):1015-1024
pubmed: 32004165
J Immunol. 2013 Sep 1;191(5):2194-204
pubmed: 23918986
Nature. 2006 Sep 21;443(7109):350-4
pubmed: 16921384
Nature. 2020 Nov;587(7833):270-274
pubmed: 32726801
Clin Vaccine Immunol. 2010 Dec;17(12):1875-80
pubmed: 20943876
Nature. 2020 Aug;584(7821):463-469
pubmed: 32717743
J Infect Dis. 2017 Mar 15;215(6):911-919
pubmed: 28453847
Open Forum Infect Dis. 2020 Nov 26;8(2):ofaa574
pubmed: 33553467
Curr HIV/AIDS Rep. 2022 Feb;19(1):5-16
pubmed: 34843064
J Clin Invest. 2021 Jun 15;131(12):
pubmed: 33945513
Nature. 2020 Aug;584(7821):457-462
pubmed: 32668444
Cell Rep Med. 2020 Jun 23;1(3):100040
pubmed: 32835303
Science. 2021 Oct 08;374(6564):eabh1823
pubmed: 34465633
J Clin Invest. 2021 Jan 4;131(1):
pubmed: 32997649
Sci Immunol. 2020 Jun 11;5(48):
pubmed: 32527802
PLoS One. 2021 Jan 25;16(1):e0245532
pubmed: 33493185
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
Hum Antibodies. 2022;30(2):105-115
pubmed: 35431235
Front Med (Lausanne). 2022 Mar 07;9:768138
pubmed: 35330585
Open Forum Infect Dis. 2021 Apr 02;8(6):ofab156
pubmed: 34095336
PLoS Pathog. 2014 May 15;10(5):e1004078
pubmed: 24831517
Respir Res. 2023 Feb 22;24(1):60
pubmed: 36814234
JCI Insight. 2020 Oct 15;5(20):
pubmed: 32937615
Cell. 2020 Nov 25;183(5):1340-1353.e16
pubmed: 33096020
Clin Infect Dis. 2022 Aug 24;75(1):e249-e256
pubmed: 34472583
Sci Immunol. 2020 Jun 26;5(48):
pubmed: 32591408
Sci Immunol. 2022 Feb 04;7(68):eabl5652
pubmed: 34914544
Front Microbiol. 2021 Jan 20;11:618097
pubmed: 33552028
Science. 2020 Oct 2;370(6512):89-94
pubmed: 32753554
Cell. 2021 Apr 29;184(9):2348-2361.e6
pubmed: 33730597
J Clin Pathol. 2023 Jun;76(6):384-390
pubmed: 35039453
Vaccines (Basel). 2022 Sep 28;10(10):
pubmed: 36298488
J Clin Invest. 2021 Jan 4;131(1):
pubmed: 33216734
Infect Dis Ther. 2021 Sep;10(3):1267-1285
pubmed: 33939121
Curr HIV/AIDS Rep. 2008 Feb;5(1):13-9
pubmed: 18417030
JCI Insight. 2021 Aug 23;6(16):
pubmed: 34251356
Elife. 2022 Jul 26;11:
pubmed: 35880744
Curr HIV/AIDS Rep. 2022 Feb;19(1):17-25
pubmed: 35113346
Nat Rev Immunol. 2020 Aug;20(8):457-458
pubmed: 32636479
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
J Leukoc Biol. 2022 Feb;111(2):355-365
pubmed: 34730247

Auteurs

Tiza L Ng'uni (TL)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.

Vernon Musale (V)

Emory-University of Georgia, Center of Excellence of Influenza Research and Surveillance (CEIRS), Lusaka, Zambia.
Center for Family Health Research in Zambia (CFHRZ), formerly Zambia Emory HIV Research Project (ZEHRP), Lusaka, Zambia.

Thandeka Nkosi (T)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.

Jonathan Mandolo (J)

Infection and Immunity Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Memory Mvula (M)

Infection and Immunity Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Clive Michelo (C)

Emory-University of Georgia, Center of Excellence of Influenza Research and Surveillance (CEIRS), Lusaka, Zambia.
Center for Family Health Research in Zambia (CFHRZ), formerly Zambia Emory HIV Research Project (ZEHRP), Lusaka, Zambia.

Farina Karim (F)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.

Mohomed Yunus S Moosa (MYS)

Human Immunodeficiency Virus (HIV) Pathogenesis Program, School of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, Durban, South Africa.

Khadija Khan (K)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.

Kondwani Charles Jambo (KC)

Infection and Immunity Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Willem Hanekom (W)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.
Division of Infection and Immunity, University College London, London, United Kingdom.

Alex Sigal (A)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.

William Kilembe (W)

Emory-University of Georgia, Center of Excellence of Influenza Research and Surveillance (CEIRS), Lusaka, Zambia.
Center for Family Health Research in Zambia (CFHRZ), formerly Zambia Emory HIV Research Project (ZEHRP), Lusaka, Zambia.

Zaza M Ndhlovu (ZM)

Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, Durban, South Africa.
Human Immunodeficiency Virus (HIV) Pathogenesis Program, School of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, Durban, South Africa.
Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA, United States.

Classifications MeSH