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

Author

Listed:
  • Nonhlanhla N. Mkhize

    (National Health Laboratory Service
    University of the Witwatersrand)

  • 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
    University of Washington
    University of Cape Town)

  • 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
    University of Washington
    Fred Hutchinson Cancer Center)

  • Yutong Jin

    (Fred Hutchinson Cancer Center)

  • Sinethemba Bhebhe

    (National Health Laboratory Service
    University of the Witwatersrand)

  • Haajira Kaldine

    (National Health Laboratory Service
    University of the Witwatersrand)

  • Prudence Kgagudi

    (National Health Laboratory Service
    University of the Witwatersrand)

  • Tandile Modise

    (National Health Laboratory Service
    University of the Witwatersrand)

  • 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
    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
    Centre for Epidemic Response & Innovation)

  • Jackline Odhiambo

    (Fred Hutchinson Cancer Center
    Chris Hani Baragwanath Academic Hospital)

  • 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
    Columbia University)

  • 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
    University of North Carolina at Chapel Hill School of Medicine)

  • 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
    Maseno University School of Medicine)

  • 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
    University of Washington)

  • Philip Kotze

    (Qhakaza Mbokodo Research Clinic)

  • Nigel Garrett

    (University of Cape Town
    University of KwaZulu–Natal
    University of KwaZulu-Natal)

  • John Hural

    (Fred Hutchinson Cancer Center)

  • Guido Ferrari

    (Duke University)

  • Erica Andersen-Nissen

    (Fred Hutchinson Cancer Center
    Hutchinson Centre Research Institute of South Africa)

  • David Montefiori

    (Duke University)

  • Penny L. Moore

    (National Health Laboratory Service
    University of the Witwatersrand
    University of KwaZulu–Natal)

  • M. Juliana McElrath

    (Fred Hutchinson Cancer Center)

  • Georgia D. Tomaras

    (Duke University)

  • Peter B. Gilbert

    (Fred Hutchinson Cancer Center
    University of Washington
    Fred Hutchinson Cancer Center)

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.

Suggested Citation

  • 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 Seato, 2025. "Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63948-4
    DOI: 10.1038/s41467-025-63948-4
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