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
Year: 2026
Type: article
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.
Source: Nature Communications
Authors: Sharon Khuzwayo, Bo Zhang, Valentin Voillet, Lindsay N. Carpp, Faatima LaherOmar, James Peng, Jiani Hu, Katharine Schwedhelm, Erica Smit, Craig A. Magaret, Zhe Chen, Siyu Heng, Yutong Jin, Peter James Elyanu, Asa Tapley, Jia Jin Kee, Aaron Hudson, Sinethemba Bhebhe, Haajira Kaldine, Prudence Kgagudi, Tandile Hermanus, Jessica Andriesen, April K. Randhawa, Leigh H. Fisher, Manuel Villaran, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C. Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, Ethel Kamuti, William Kilembe, Fatima Laher, Joseph Makhema, Moelo Malahleha, Vongane Louisa Maluleke, Matsontso Mathebula, Grace Mboya, Kirsten McHarry, Cissy Kityo Mutuluuza, Pamela Mda, Essack Mitha, Sibekezelo Msomi, Tumelo Moloantoa, Nivashnee Naicker, Vimla Naicker, Annet Nanvubya, Harriet Nuwagaba-Biribonwoha, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil AbdulKadir Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Joel Maena, Myron S. Cohen, James G. Kublin, Linda- Gail Bekker, Lawrence Corey, Glenda E. Gray, Yunda Huang, Nyaradzo M. Mgodi, Sufia Dadabhai, Philip L. Kotze, Nigel Garrett, John Hural, Guido Ferrari, David Montefiori, Penny L. Moore, Georgia D. Tomaras, Nonhlanhla N. Mkhize, Stephen C. De Rosa, M. Juliana McElrath, Peter B. Gilbert, Erica Andersen-Nissen, for the CoVPN 3008 Study Team
Institutions: Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa, Fred Hutch Cancer Center, University of Washington, University of Pennsylvania, New York University, Baylor College of Medicine Children’s Foundation, University of Cape Town, National Health Laboratory Service, South African Medical Research Council, University of the Witwatersrand, National Institute for Communicable Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of Zimbabwe, Aurum Institute, Task Applied Science, Stellenbosch University, University of North Carolina at Chapel Hill, Soweto CTC, Johns Hopkins University, Centre for Infectious Disease Research in Zambia, Botswana Harvard AIDS Institute Partnership, Joint Clinical Research Centre, Walter Sisulu University, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, International AIDS Vaccine Initiative, UVRI-CRP Initiative, Uganda Virus Research Institute, ICAP Global Health, Columbia University, Maseno University, Kitovu Hospital, Moi University, MUJHU Research Collaboration, Duke University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: International AIDS Vaccine Initiative, Fred Hutchinson Cancer Research Center, Emory University, Johns Hopkins University, South African Medical Research Council, Inyuvesi Yakwazulu-Natali, National Commission for Science, Technology and Innovation, University of Cape Town, Uganda National Council for Science and Technology, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Office of Research Infrastructure Programs, National Institutes of Health
Awards: G1131636781, G1384187122, G1636177350, G4681072085, G7522203623, G8343818084, G9000009643, G9000028484, HIV Vaccine Trials Network Laboratory Center, SDMC: HIV Vaccine Trials Network, Statistical Methods for Efficacy Trials of Vaccines and Monoclonal Antibodies Against Genetically-Diverse Pathogens, Host Defense Training in Allergy and Infectious Diseases
OpenAlex ID: W7214552430