Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study

Linda-Gail Bekker, Nigel Garrett, Ameena Goga, Lara Fairall, Tarylee Reddy, Nonhlanhla Yende-Zuma, Reshma Kassanjee, Shirley Collie, Ian Sanne, Andrew Boulle, Ishen Seocharan, Imke Engelbrecht, Mary-Ann Davies, Jared Champion, Tommy Chen, Sarah Bennett, Selaelo Mametja, Mabatlo Semenya, Harry Moultrie, Tulio de Oliveira, Richard John Lessells, Cheryl Cohen, Waasila Jassat, Michelle Groome, Anne Von Gottberg, Engelbert Le Roux, Kentse Khuto, Dan Barouch, Hassan Mahomed, Milani Wolmarans, Petro Rousseau, Debbie Bradshaw, Michelle Mulder, Jessica Opie, Vernon Louw, Barry Jacobson, Pradeep Rowji, Jonny G Peter, Azwi Takalani, Jackline Odhiambo, Fatima Mayat, Simbarashe Takuva, Lawrence Corey, Glenda E Gray, Sisonke Protocol Team, Sisonke Study Team, William Brumskine, Nivashnee Naicker, Disebo Makhaza, Vimla Naicker, Logashvari Naidoo, Elizabeth Spooner, Elane van Nieuwenhuizen, Kathryn Mngadi, Maphoshane Nchabeleng, James Craig Innes, Katherine Gill, Friedrich Georg Petrick, Shaun Barnabas, Sharlaa Badal-Faesen, Sheetal Kassim, Scott Hayden Mahoney, Erica Lazarus, Anusha Nana, Rebone Molobane Maboa, Philip Kotze, Johan Lombaard, Daniel Rudolf Malan, Sheena Kotze, Phuthi Mohlala, Amy Ward, Graeme Meintjes, Dorothea Urbach, Faeezah Patel, Andreas Diacon, Khatija Ahmed, Coert Grobbelaar, Pamela Mda, Thozama Dubula, Angelique Luabeya, Musawenkosi Bhekithemba Mamba, Lesley Burgess, Rodney Dawson, Linda-Gail Bekker, Nigel Garrett, Ameena Goga, Lara Fairall, Tarylee Reddy, Nonhlanhla Yende-Zuma, Reshma Kassanjee, Shirley Collie, Ian Sanne, Andrew Boulle, Ishen Seocharan, Imke Engelbrecht, Mary-Ann Davies, Jared Champion, Tommy Chen, Sarah Bennett, Selaelo Mametja, Mabatlo Semenya, Harry Moultrie, Tulio de Oliveira, Richard John Lessells, Cheryl Cohen, Waasila Jassat, Michelle Groome, Anne Von Gottberg, Engelbert Le Roux, Kentse Khuto, Dan Barouch, Hassan Mahomed, Milani Wolmarans, Petro Rousseau, Debbie Bradshaw, Michelle Mulder, Jessica Opie, Vernon Louw, Barry Jacobson, Pradeep Rowji, Jonny G Peter, Azwi Takalani, Jackline Odhiambo, Fatima Mayat, Simbarashe Takuva, Lawrence Corey, Glenda E Gray, Sisonke Protocol Team, Sisonke Study Team, William Brumskine, Nivashnee Naicker, Disebo Makhaza, Vimla Naicker, Logashvari Naidoo, Elizabeth Spooner, Elane van Nieuwenhuizen, Kathryn Mngadi, Maphoshane Nchabeleng, James Craig Innes, Katherine Gill, Friedrich Georg Petrick, Shaun Barnabas, Sharlaa Badal-Faesen, Sheetal Kassim, Scott Hayden Mahoney, Erica Lazarus, Anusha Nana, Rebone Molobane Maboa, Philip Kotze, Johan Lombaard, Daniel Rudolf Malan, Sheena Kotze, Phuthi Mohlala, Amy Ward, Graeme Meintjes, Dorothea Urbach, Faeezah Patel, Andreas Diacon, Khatija Ahmed, Coert Grobbelaar, Pamela Mda, Thozama Dubula, Angelique Luabeya, Musawenkosi Bhekithemba Mamba, Lesley Burgess, Rodney Dawson

Abstract

Background: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic.

Methods: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 1010 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual.

Findings: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]).

Interpretation: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally.

Funding: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.

Conflict of interest statement

Declaration of interests L-GB declares honoraria for advisory roles from MSD, ViiV Health Care, and Gilead. RJL declares Department of Science and Innovation and South African Medical Research Council (SAMRC) funding to the KwaZulu-Natal Research Innovation and Sequencing Platform at the University of KwaZulu-Natal for the Network for Genomic Surveillance South Africa, which supported the genomic sequencing for this study; and committee membership of the Ministerial Advisory Committee on COVID-19 Vaccines (a committee that makes recommendations to the Minister of South Africa on the national COVID-19 vaccine programme. CC declares grants or contracts from CDC, PATH, the Bill & Melinda Gates Foundation, SAMRC, Wellcome Trust, and Sanofi Pasteur in the past 36 months. MG reports grants from SAMRC during the conduct of the study, and grants from the Bill & Melinda Gates Foundation outside of the submitted work. DBa reports grants from US National Institutes of Health (NIH) and Janssen during the conduct of the study; grants from Defense Advanced Research projects Agency, Massachusetts Consortium on Pathogen Readiness, Ragon Institute, the Bill & Melinda Gates Foundation, SAMRC, Henry Jackson Foundation, Musk Foundation, Gilead, Legend Bio, CureVac, Sanofi, Intima Bio, Alkermes, and Zentalis; and personal fees from SZQ Bio, Pfizer, Celsion, Avidea, Laronde, Meissa, and Vector Sciences outside of the submitted work DBr has three patents (63/121,482; 63/133,969; 63/135,182) licensed to Janssen. All other authors declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Trial profile Sisonke participants were matched with unvaccinated controls on age, sex, number of comorbidities, geographical location (health district), socioeconomic status (by scheme plan option for scheme A and income level for scheme B), and, for scheme A, previous SARS-CoV-2 infection (could not be matched for scheme B due to paucity of data available).*Includes 2027 individuals who were also included in the Western Cape provincial dataset. †Includes 13 135 individuals who were also included in the Western Cape provincial dataset.
Figure 2
Figure 2
Cumulative incidence of primary COVID-19 outcomes in vaccinated and unvaccinated insured individuals (schemes A and B) by time since vaccination or matching (A) COVID-19-related hospital admissions. (B) COVID-19-related hospital admissions requiring critical or intensive care. (C) COVID-19-related deaths. Solid lines show the cumulative incidence, with shaded areas showing 95% CIs. Number censored at each timepoint is in the appendix (p 17).

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Source: PubMed

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