Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV

Nonhlanhla N. Mkhize, Bo Zhang, Caroline Brackett, Peter James Elyanu, Asa Tapley, Sufia Dadabhai, Jiani Hu, Bich T. N. Do, Daniel J. Schuster, Jack Heptinstall, Sheetal Sawant, Kelly Seaton, Marcella Sarzotti-Kelsoe, Aaron Hudson, Yutong Jin, Sinethemba Bhebhe, Haajira Kaldine, Prudence Kgagudi, Tandile Modise, Nyaradzo M. Mgodi, Jessica Andriesen, April K. Randhawa, Leigh H. Fisher, Jia Jin Kee, Craig A. Magaret, James Peng, Avi Kenny, Lindsay N. Carpp, Zhe Chen, Siyu Heng, Manuel Villaran, Azwidihwi Takalani, Bert Roux, Eduan Wilkinson, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Joseph Makhema, Ethel Kamuti, Katanekwa Njekwa, Harriet Nuwagaba-Biribonwoha, Allan Baguma, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Gill, Anda Madikida, Zaheer Ahmed Ebrahim Hoosain, Mina C. Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Humphrey Mwape, Priya Kassim, Melvin C. Kamanga, William Kilembe, Fatima Laher, Mookho Malahleha, Vongane Louisa Maluleke, Grace Mboya, Philister Adhiambo Madiega, Kirsten McHarry, Essack Mitha, Yajna Duki, Pamela Mda, Moroesi Moerane, Tumelo Moloantoa, Simpson Nuwamanya, Sharana Mahomed, Vimla Naicker, Anusha Nana, Annet Nanvubya, Barbarah Kawoozo, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Sheetal Kassim, Dorothie Vendt, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, James G. Kublin, Linda-Gail Bekker, Lawrence Corey, Glenda E. Gray, Yunda Huang, Philip Kotze, Nigel Garrett, John Hural, Guido Ferrari, Erica Andersen-Nissen, David Montefiori, Penny L. Moore, M. Juliana McElrath, Georgia D. Tomaras () and Peter B. Gilbert ()
Additional contact information
Nonhlanhla N. Mkhize: National Health Laboratory Service
Bo Zhang: Fred Hutchinson Cancer Center
Caroline Brackett: Duke University
Peter James Elyanu: Baylor College of Medicine Children’s Foundation-Uganda
Asa Tapley: Fred Hutchinson Cancer Center
Sufia Dadabhai: Johns Hopkins Research Project
Jiani Hu: Fred Hutchinson Cancer Center
Bich T. N. Do: Duke University
Daniel J. Schuster: Duke University
Jack Heptinstall: Duke University
Sheetal Sawant: Duke University
Kelly Seaton: Duke University
Marcella Sarzotti-Kelsoe: Duke University
Aaron Hudson: Fred Hutchinson Cancer Center
Yutong Jin: Fred Hutchinson Cancer Center
Sinethemba Bhebhe: National Health Laboratory Service
Haajira Kaldine: National Health Laboratory Service
Prudence Kgagudi: National Health Laboratory Service
Tandile Modise: National Health Laboratory Service
Nyaradzo M. Mgodi: University of Zimbabwe
Jessica Andriesen: Fred Hutchinson Cancer Center
April K. Randhawa: Fred Hutchinson Cancer Center
Leigh H. Fisher: Fred Hutchinson Cancer Center
Jia Jin Kee: Fred Hutchinson Cancer Center
Craig A. Magaret: Fred Hutchinson Cancer Center
James Peng: University of Washington
Avi Kenny: Duke University
Lindsay N. Carpp: Fred Hutchinson Cancer Center
Zhe Chen: University of Pennsylvania
Siyu Heng: New York University
Manuel Villaran: Fred Hutchinson Cancer Center
Azwidihwi Takalani: Chris Hani Baragwanath Academic Hospital
Bert Roux: Chris Hani Baragwanath Academic Hospital
Eduan Wilkinson: University of KwaZulu-Natal
Jackline Odhiambo: Fred Hutchinson Cancer Center
Parth Shah: Fred Hutchinson Cancer Center
Laura Polakowski: National Institutes of Health
Margaret Yacovone: National Institutes of Health
Taraz Samandari: COVID-19 Prevention Network
Zvavahera Chirenje: University of Zimbabwe
Joseph Makhema: Botswana Harvard AIDS Institute
Ethel Kamuti: Centre for Infectious Disease Research in Zambia
Katanekwa Njekwa: Centre for Infectious Disease Research in Zambia
Harriet Nuwagaba-Biribonwoha: Eswatini Prevention Center
Allan Baguma: Baylor College of Medicine Children’s Foundation-Uganda
Sharlaa Badal-Faesen: Clinical HIV Research Unit / Helen Joseph Clinical Research Site
William Brumskine: Rustenburg Clinical Research Site
Soritha Coetzer: Synexus Helderberg
Rodney Dawson: University of Cape Town Lung Institute Clinical Research Site
Sinead Delany-Moretlwe: Wits RHI University of the Witwatersrand
Andreas Henri Diacon: TASK
Samantha Fry: FAMCRU Family Clinical Research Unit
Katherine Gill: University of Cape Town
Anda Madikida: University of Cape Town
Zaheer Ahmed Ebrahim Hoosain: Josha Research Clinical Research Site
Mina C. Hosseinipour: Malawi Clinical Research Site
Mubiana Inambao: CFHRZ - Ndola Clinical Research Site
Craig Innes: Klerksdorp Clinical Research Site
Steve Innes: University of Cape Town
Dishiki Kalonji: Isipingo Clinical Research Site
Humphrey Mwape: UNC Global Projects / Kamwala District Health Centre
Priya Kassim: Soweto - Kliptown Clinical Research Site
Melvin C. Kamanga: Johns Hopkins Research Project-Kamuzu University of Health Sciences
William Kilembe: CFHRZ Clinical Research Site
Fatima Laher: University of the Witwatersrand
Mookho Malahleha: Synergy Biomed Research Institute
Vongane Louisa Maluleke: MERC Middelburg
Grace Mboya: Kisumu Clinical Research Site
Philister Adhiambo Madiega: Kenya Medical Research Institute
Kirsten McHarry: TASK Eden
Essack Mitha: Newtown Clinical Research
Yajna Duki: Aurum Tembisa Clinic 4
Pamela Mda: Walter Sisulu University
Moroesi Moerane: Walter Sisulu University
Tumelo Moloantoa: PHRU Matlosana Clinical Research Site
Simpson Nuwamanya: Joint Clinical Research Centre
Sharana Mahomed: University of KwaZulu–Natal
Vimla Naicker: Tongaat Clinical Research Site
Anusha Nana: Soweto - Kliptown Clinical Research Site
Annet Nanvubya: UVRI-IAVI HIV Vaccine Program Ltd. Clinical Research Site
Barbarah Kawoozo: UVRI-IAVI HIV Vaccine Program Ltd. Clinical Research Site
Maphoshane Nchabeleng: MeCRU Clinical Research Site
Walter Otieno: Kombewa Clinical Research Site
Elsje Louise Potgieter: Synexus Stanza Clinical Research Centre Clinical Research Site
Disebo Potloane: University of KwaZulu–Natal
Zelda Punt: PHOENIX Pharma (Pty) Ltd
Jamil Said: Moi University Clinical Research Centre
Yashna Singh: University of Cape Town
Sheetal Kassim: University of Cape Town
Dorothie Vendt: University of Cape Town
Mohammed Siddique Tayob: MERC Kempton
Yacoob Vahed: MERC Welkom
Deo Ogema Wabwire: MU-JHU Research Collaboration Clinical Research Site
James G. Kublin: Fred Hutchinson Cancer Center
Linda-Gail Bekker: University of Cape Town
Lawrence Corey: Fred Hutchinson Cancer Center
Glenda E. Gray: South African Medical Research Council
Yunda Huang: Fred Hutchinson Cancer Center
Philip Kotze: Qhakaza Mbokodo Research Clinic
Nigel Garrett: University of Cape Town
John Hural: Fred Hutchinson Cancer Center
Guido Ferrari: Duke University
Erica Andersen-Nissen: Fred Hutchinson Cancer Center
David Montefiori: Duke University
Penny L. Moore: National Health Laboratory Service
M. Juliana McElrath: Fred Hutchinson Cancer Center
Georgia D. Tomaras: Duke University
Peter B. Gilbert: Fred Hutchinson Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.

Date: 2025
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DOI: 10.1038/s41467-025-63948-4

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