tetano
Editor, Senior Moderator
Nat Commun
. 2026 Sep 28;17(1):11173.
doi: 10.1038/s41467-026-77995-y.
Sharon Khuzwayo # 1 , Bo Zhang # 2 , Valentin Voillet # 1 2 , Lindsay N Carpp 2 , Faatima LaherOmar 1 , James Peng 3 , Jiani Hu 2 , Katharine Schwedhelm 2 , Erica Smit 1 , Craig A Magaret 2 , Zhe Chen 4 , Siyu Heng 5 , Yutong Jin 2 , Peter James Elyanu 6 , Asa Tapley 7 8 , Jia Jin Kee 2 , Aaron Hudson 2 3 9 , Sinethemba Bhebhe 10 11 , Haajira Kaldine 10 11 , Prudence Kgagudi 10 11 , Tandile Hermanus 10 11 , Jessica Andriesen 2 , April K Randhawa 2 , Leigh H Fisher 2 , Manuel Villaran 2 , Laura Polakowski 12 , Margaret Yacovone 12 , Taraz Samandari 13 , Zvavahera Chirenje 14 , Sharlaa Badal-Faesen 15 , William Brumskine 16 , Soritha Coetzer 17 , Rodney Dawson 18 , Sinead Delany-Moretlwe 19 , Andreas Henri Diacon 20 , Samantha Fry 21 , Katherine Margaret Gill 8 , Zaheer Ahmed Ebrahim Hoosain 22 , Mina C Hosseinipour 23 24 , Mubiana Inambao 25 , Craig Innes 26 , Steve Innes 8 , Dishiki Kalonji 27 , Margaret Kasaro 28 , Priya Kassim 29 , Noel Kayange 30 , Ethel Kamuti 31 , William Kilembe 32 , Fatima Laher 33 , Joseph Makhema 34 , Moelo Malahleha 35 , Vongane Louisa Maluleke 36 , Matsontso Mathebula 37 , Grace Mboya 38 , Kirsten McHarry 39 , Cissy Kityo Mutuluuza 40 , Pamela Mda 41 , Essack Mitha 42 , Sibekezelo Msomi 43 , Tumelo Moloantoa 44 , Nivashnee Naicker 45 , Vimla Naicker 46 , Annet Nanvubya 47 , Harriet Nuwagaba-Biribonwoha 48 49 , Walter Otieno 50 51 , Elsje Louise Potgieter 52 , Disebo Potloane 45 , Zelda Punt 53 , Jamil AbdulKadir Said 54 , Yashna Singh 8 , Mohammed Siddique Tayob 55 , Yacoob Vahed 56 , Joel Maena 57 , Myron S Cohen 58 , James G Kublin 2 , Linda- Gail Bekker 8 , Lawrence Corey 2 7 59 , Glenda E Gray 33 60 , Yunda Huang 2 61 , Nyaradzo M Mgodi 14 , Sufia Dadabhai 62 , Philip L Kotze 63 , Nigel Garrett 8 45 64 , John Hural 2 , Guido Ferrari 65 , David Montefiori 65 , Penny L Moore 10 11 45 , Georgia D Tomaras 65 , Nonhlanhla N Mkhize 10 11 , Stephen C De Rosa 2 59 , M Juliana McElrath 2 , Peter B Gilbert 66 67 68 , Erica Andersen-Nissen 69 70 ; CoVPN 3008 Study Team
Affiliations Expand
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.
. 2026 Sep 28;17(1):11173.
doi: 10.1038/s41467-026-77995-y.
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
Sharon Khuzwayo # 1 , Bo Zhang # 2 , Valentin Voillet # 1 2 , Lindsay N Carpp 2 , Faatima LaherOmar 1 , James Peng 3 , Jiani Hu 2 , Katharine Schwedhelm 2 , Erica Smit 1 , Craig A Magaret 2 , Zhe Chen 4 , Siyu Heng 5 , Yutong Jin 2 , Peter James Elyanu 6 , Asa Tapley 7 8 , Jia Jin Kee 2 , Aaron Hudson 2 3 9 , Sinethemba Bhebhe 10 11 , Haajira Kaldine 10 11 , Prudence Kgagudi 10 11 , Tandile Hermanus 10 11 , Jessica Andriesen 2 , April K Randhawa 2 , Leigh H Fisher 2 , Manuel Villaran 2 , Laura Polakowski 12 , Margaret Yacovone 12 , Taraz Samandari 13 , Zvavahera Chirenje 14 , Sharlaa Badal-Faesen 15 , William Brumskine 16 , Soritha Coetzer 17 , Rodney Dawson 18 , Sinead Delany-Moretlwe 19 , Andreas Henri Diacon 20 , Samantha Fry 21 , Katherine Margaret Gill 8 , Zaheer Ahmed Ebrahim Hoosain 22 , Mina C Hosseinipour 23 24 , Mubiana Inambao 25 , Craig Innes 26 , Steve Innes 8 , Dishiki Kalonji 27 , Margaret Kasaro 28 , Priya Kassim 29 , Noel Kayange 30 , Ethel Kamuti 31 , William Kilembe 32 , Fatima Laher 33 , Joseph Makhema 34 , Moelo Malahleha 35 , Vongane Louisa Maluleke 36 , Matsontso Mathebula 37 , Grace Mboya 38 , Kirsten McHarry 39 , Cissy Kityo Mutuluuza 40 , Pamela Mda 41 , Essack Mitha 42 , Sibekezelo Msomi 43 , Tumelo Moloantoa 44 , Nivashnee Naicker 45 , Vimla Naicker 46 , Annet Nanvubya 47 , Harriet Nuwagaba-Biribonwoha 48 49 , Walter Otieno 50 51 , Elsje Louise Potgieter 52 , Disebo Potloane 45 , Zelda Punt 53 , Jamil AbdulKadir Said 54 , Yashna Singh 8 , Mohammed Siddique Tayob 55 , Yacoob Vahed 56 , Joel Maena 57 , Myron S Cohen 58 , James G Kublin 2 , Linda- Gail Bekker 8 , Lawrence Corey 2 7 59 , Glenda E Gray 33 60 , Yunda Huang 2 61 , Nyaradzo M Mgodi 14 , Sufia Dadabhai 62 , Philip L Kotze 63 , Nigel Garrett 8 45 64 , John Hural 2 , Guido Ferrari 65 , David Montefiori 65 , Penny L Moore 10 11 45 , Georgia D Tomaras 65 , Nonhlanhla N Mkhize 10 11 , Stephen C De Rosa 2 59 , M Juliana McElrath 2 , Peter B Gilbert 66 67 68 , Erica Andersen-Nissen 69 70 ; CoVPN 3008 Study Team
Affiliations Expand
- PMID: 42946742
- DOI: 10.1038/s41467-026-77995-y
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.