Peer-reviewedCC BY-NC-ND 4.0Nature Communications
mRNA-1273 SARS-CoV-2 vaccination in people with HIV: an immune correlates analysis of CD4 + T cell responses in the multicenter CoVPN 3008 observational study
40 affiliations
- 1Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
- 2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA USA
- 3Department of Biostatistics, University of Washington, Seattle, WA USA
- 4Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA USA
- 5Department of Biostatistics, School of Global Public Health, New York University, New York, NY USA
- 6Baylor College of Medicine Children’s Foundation-Uganda, Kampala, Uganda
- 7Department of Medicine, University of Washington, Seattle, WA USA
- 8Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
- 9Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA
- 10SAMRC Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- 11National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa
- 12National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
- 13COVID-19 Prevention Network, Seattle, Washington USA
- 14Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe
- 15Clinical HIV Research Unit (CHRU), Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
- 16The Aurum Institute, Rustenburg Clinical Research Site, Rustenburg, South Africa
- 17Synexus Helderberg, Cape Town, South Africa
- 18University of Cape Town Lung Institute Clinical Research Site, Cape Town, South Africa
- 19Wits RHI University of the Witwatersrand, Johannesburg, South Africa
- 20TASK, Cape Town, South Africa
- 21Department of Paediatrics and Child Health, FAMCRU (Family Centre for Research with Ubuntu), Stellenbosch University, Cape Town, South Africa
- 22Josha Research Clinical Research Site, Bloemfontein, South Africa
- 23Malawi Clinical Research Site, Lilongwe, Malawi
- 24University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, CA USA
- 25CFHRZ - Ndola Clinical Research Site, Ndola, Zambia
- 26The Aurum Institute, Klerksdorp Clinical Research Site, Klerksdorp, South Africa
- 27South African Medical Research Council, Isipingo Clinical Research Site, KwaZulu-Natal, South Africa
- 28UNC Global Projects / Kamwala District Health Centre, Lusaka, Zambia
- 29Soweto - Kliptown Clinical Research Site, Soweto, South Africa
- 30Johns Hopkins Research Project (Blantyre CRS), Blantyre, Malawi
- 31Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- 32CFHRZ Clinical Research Site, Lusaka, Zambia
- 33Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa
- 34Botswana Harvard AIDS Institute, Gaborone, Botswana
- 35Synergy Biomed Research Institute, East London, South Africa
- 36MERC Middelburg, Middelburg, South Africa
- 37MeCRU CRS, Pretoria, Ga-Rankuwa South Africa
- 38Kisumu Clinical Research Site, Kisumu, Kenya
- 39TASK Eden, Western Cape, South Africa
- 40Joint Clinical Research Centre Lubowa, Lubowa, Uganda
Abstract
T cell correlates of COVID-19 risk are poorly defined, particularly in people with HIV (PWH). CoVPN 3008 (NCT05168813) Part A was a prospective 14,002-participant cohort study that administered one or two doses of mRNA-1273 COVID-19 vaccine, depending on baseline SARS-CoV-2 serostatus, in participants (83% PWH) in sub-Saharan Africa. Participants self-monitored for prespecified COVID-19 symptoms, defined by Centers for Disease Control and Prevention symptom criteria. Previous work showed that protection from COVID-19 was superior for hybrid versus vaccine-induced immunity, and that neutralizing antibody titers inversely associated with COVID-19 risk. In the present work, we measured T cell responses to Spike and Nucleocapsid at baseline and 4 weeks post last-vaccination (Peak) in a case-cohort study and assessed them as correlates of risk. In Hybrid Group PWH (n = 22 cases), COVID-19 risk over 6 months decreased with increasing Peak Spike BA.4/5-specific CD4 + T cell responses, from 15.8%, 4.7%, and 0% risk at 0.1%, 0.2%, and 0.3% IFN-γ and/or IL-2 response magnitude, respectively. Including baseline Spike-specific neutralizing antibody titer and Peak CD4 + T cell functionality score in the same model increased the association’s strength (overall p < 0.001). Thus, CD4 + T cell responses are an independent correlate of COVID-19 risk among PWH with pre-existing SARS-CoV-2 immunity.
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BibTeX
@article{khuzwayo2026mrna1273,
title = {{mRNA-1273 SARS-CoV-2 vaccination in people with HIV: an immune correlates analysis of CD4 + T cell responses in the multicenter CoVPN 3008 observational study}},
author = {Sharon Khuzwayo and Bo Zhang and Valentin Voillet and Lindsay N. Carpp and Faatima LaherOmar and James Peng and Jiani Hu and Katharine Schwedhelm and Erica Smit and Craig A. Magaret and Zhe Chen and Siyu Heng and Yutong Jin and Peter James Elyanu and Asa Tapley and Jia Jin Kee and Aaron Hudson and Sinethemba Bhebhe and Haajira Kaldine and Prudence Kgagudi and Tandile Hermanus and Jessica Andriesen and April K. Randhawa and Leigh H. Fisher and Manuel Villaran and Laura Polakowski and Margaret Yacovone and Taraz Samandari and Zvavahera Chirenje and Sharlaa Badal-Faesen and William Brumskine and Soritha Coetzer and Rodney Dawson and Sinead Delany-Moretlwe and Andreas Henri Diacon and Samantha Fry and Katherine Margaret Gill and Zaheer Ahmed Ebrahim Hoosain and Mina C. Hosseinipour and Mubiana Inambao and Craig Innes and Steve Innes and Dishiki Kalonji and Margaret Kasaro and Priya Kassim and Noel Kayange and Ethel Kamuti and William Kilembe and Fatima Laher and Joseph Makhema and Moelo Malahleha and Vongane Louisa Maluleke and Matsontso Mathebula and Grace Mboya and Kirsten McHarry and Cissy Kityo Mutuluuza and Pamela Mda and Essack Mitha and Sibekezelo Msomi and Tumelo Moloantoa},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77995-y},
url = {https://doi.org/10.1038/s41467-026-77995-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - mRNA-1273 SARS-CoV-2 vaccination in people with HIV: an immune correlates analysis of CD4 + T cell responses in the multicenter CoVPN 3008 observational study
AU - Sharon Khuzwayo
AU - Bo Zhang
AU - Valentin Voillet
AU - Lindsay N. Carpp
AU - Faatima LaherOmar
AU - James Peng
AU - Jiani Hu
AU - Katharine Schwedhelm
AU - Erica Smit
AU - Craig A. Magaret
AU - Zhe Chen
AU - Siyu Heng
AU - Yutong Jin
AU - Peter James Elyanu
AU - Asa Tapley
AU - Jia Jin Kee
AU - Aaron Hudson
AU - Sinethemba Bhebhe
AU - Haajira Kaldine
AU - Prudence Kgagudi
AU - Tandile Hermanus
AU - Jessica Andriesen
AU - April K. Randhawa
AU - Leigh H. Fisher
AU - Manuel Villaran
AU - Laura Polakowski
AU - Margaret Yacovone
AU - Taraz Samandari
AU - Zvavahera Chirenje
AU - Sharlaa Badal-Faesen
AU - William Brumskine
AU - Soritha Coetzer
AU - Rodney Dawson
AU - Sinead Delany-Moretlwe
AU - Andreas Henri Diacon
AU - Samantha Fry
AU - Katherine Margaret Gill
AU - Zaheer Ahmed Ebrahim Hoosain
AU - Mina C. Hosseinipour
AU - Mubiana Inambao
AU - Craig Innes
AU - Steve Innes
AU - Dishiki Kalonji
AU - Margaret Kasaro
AU - Priya Kassim
AU - Noel Kayange
AU - Ethel Kamuti
AU - William Kilembe
AU - Fatima Laher
AU - Joseph Makhema
AU - Moelo Malahleha
AU - Vongane Louisa Maluleke
AU - Matsontso Mathebula
AU - Grace Mboya
AU - Kirsten McHarry
AU - Cissy Kityo Mutuluuza
AU - Pamela Mda
AU - Essack Mitha
AU - Sibekezelo Msomi
AU - Tumelo Moloantoa
PY - 2026
DA - 2026/09/28
JO - Nature Communications
DO - 10.1038/s41467-026-77995-y
UR - https://doi.org/10.1038/s41467-026-77995-y
AB - T cell correlates of COVID-19 risk are poorly defined, particularly in people with HIV (PWH). CoVPN 3008 (NCT05168813) Part A was a prospective 14,002-participant cohort study that administered one or two doses of mRNA-1273 COVID-19 vaccine, depending on baseline SARS-CoV-2 serostatus, in participants (83% PWH) in sub-Saharan Africa. Participants self-monitored for prespecified COVID-19 symptoms, defined by Centers for Disease Control and Prevention symptom criteria. Previous work showed that protection from COVID-19 was superior for hybrid versus vaccine-induced immunity, and that neutralizing antibody titers inversely associated with COVID-19 risk. In the present work, we measured T cell responses to Spike and Nucleocapsid at baseline and 4 weeks post last-vaccination (Peak) in a case-cohort study and assessed them as correlates of risk. In Hybrid Group PWH (n = 22 cases), COVID-19 risk over 6 months decreased with increasing Peak Spike BA.4/5-specific CD4 + T cell responses, from 15.8%, 4.7%, and 0% risk at 0.1%, 0.2%, and 0.3% IFN-γ and/or IL-2 response magnitude, respectively. Including baseline Spike-specific neutralizing antibody titer and Peak CD4 + T cell functionality score in the same model increased the association’s strength (overall p < 0.001). Thus, CD4 + T cell responses are an independent correlate of COVID-19 risk among PWH with pre-existing SARS-CoV-2 immunity.
SN - 2041-1723
ER -