. 2022 Mar 19;399(10330):1141-1153.

doi: 10.1016/S0140-6736(22)00007-1.

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 Bekker¹, Nigel Garrett², Ameena Goga³, Lara Fairall⁴, Tarylee Reddy⁵, Nonhlanhla Yende-Zuma⁶, Reshma Kassanjee⁷, Shirley Collie⁸, Ian Sanne⁹, Andrew Boulle¹⁰, Ishen Seocharan⁵, Imke Engelbrecht¹¹, Mary-Ann Davies¹², Jared Champion⁸, Tommy Chen⁸, Sarah Bennett¹³, Selaelo Mametja¹⁴, Mabatlo Semenya¹⁴, Harry Moultrie¹⁵, Tulio de Oliveira¹⁶, Richard John Lessells¹⁶, Cheryl Cohen¹⁷, Waasila Jassat¹⁸, Michelle Groome¹⁹, Anne Von Gottberg²⁰, Engelbert Le Roux²¹, Kentse Khuto²¹, Dan Barouch²², Hassan Mahomed²³, Milani Wolmarans²⁴, Petro Rousseau²⁴, Debbie Bradshaw²⁵, Michelle Mulder²⁶, Jessica Opie²⁷, Vernon Louw²⁸, Barry Jacobson²⁹, Pradeep Rowji³⁰, Jonny G Peter³¹, Azwi Takalani²¹, Jackline Odhiambo²¹, Fatima Mayat³², Simbarashe Takuva³³, Lawrence Corey³⁴, Glenda E Gray³⁵; Sisonke Protocol Team; Sisonke Study Team

Collaborators, Affiliations

Collaborators

Affiliations

¹ The Desmond Tutu HIV Centre, Cape Town, South Africa; University of Cape Town, Cape Town, South Africa.
² Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
³ HIV Prevention Research Unit, Cape Town, South Africa; Department of Paediatrics and Child Health, University of Pretoria, Pretoria, South Africa.
⁴ The Desmond Tutu HIV Centre, Cape Town, South Africa; King's Global Health Institute, King's College London, London, UK.
⁵ Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa.
⁶ Nelson R Mandela School of Medicine, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
⁷ Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa.
⁸ Discovery Health, Sandton, South Africa.
⁹ Clinical HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Right to Care, Houghton South Africa.
¹⁰ Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa; Western Cape Government Health, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa.
¹¹ Right to Care, Centurion, South Africa.
¹² Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa; Western Cape Government: Health Centre for Infectious Disease Epidemiology and Research, Cape Town, South Africa.
¹³ Medscheme, Cape Town, South Africa.
¹⁴ Government Employees Medical Scheme, Pretoria, South Africa.
¹⁵ Centre for Tuberculosis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁶ KwaZulu-Natal Research Innovation, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁷ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁸ National Institute for Communicable Diseases, Sandringham, South Africa.
¹⁹ School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
²⁰ Department of Pathology, Cape Town, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
²¹ Hutchinson Center Research Institute of South Africa (HCRISA), Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.
²² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
²³ Metro Health Services, Western Cape Government Health, Cape Town, South Africa; Division of Health Systems and Public Health, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
²⁴ National Department of Health, Pretoria, South Africa.
²⁵ South African Medical Research Council, Tygerberg, South Africa.
²⁶ South Africa Medical Research Council, Cape Town, South Africa.
²⁷ University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Cape Town, South Africa.
²⁸ Division of Clinical Haematology, Department of Medicine, Cape Town, South Africa; Groote Schuur Hospital, Cape Town, South Africa.
²⁹ Faculty of Health Sciences, and Allergy and Immunology Unit, Cape Town, South Africa.
³⁰ Neurology Association of South Africa, The Southern African Society of Thrombosis and Haemostasis, Johannesburg, South Africa.
³¹ Division of Allergy and Clinical Immunology, Cape Town, South Africa.
³² Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Witwatersrand, South Africa.
³³ School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁵ South Africa Medical Research Council, Cape Town, South Africa. Electronic address: glenda.gray@mrc.ac.za.

PMID: 35305740
PMCID: PMC8930006
DOI: 10.1016/S0140-6736(22)00007-1

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 et al. Lancet. 2022.

. 2022 Mar 19;399(10330):1141-1153.

doi: 10.1016/S0140-6736(22)00007-1.

Authors

Collaborators

Affiliations

¹ The Desmond Tutu HIV Centre, Cape Town, South Africa; University of Cape Town, Cape Town, South Africa.
² Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
³ HIV Prevention Research Unit, Cape Town, South Africa; Department of Paediatrics and Child Health, University of Pretoria, Pretoria, South Africa.
⁴ The Desmond Tutu HIV Centre, Cape Town, South Africa; King's Global Health Institute, King's College London, London, UK.
⁵ Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa.
⁶ Nelson R Mandela School of Medicine, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
⁷ Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa.
⁸ Discovery Health, Sandton, South Africa.
⁹ Clinical HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Right to Care, Houghton South Africa.
¹⁰ Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa; Western Cape Government Health, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa.
¹¹ Right to Care, Centurion, South Africa.
¹² Centre of Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa; Western Cape Government: Health Centre for Infectious Disease Epidemiology and Research, Cape Town, South Africa.
¹³ Medscheme, Cape Town, South Africa.
¹⁴ Government Employees Medical Scheme, Pretoria, South Africa.
¹⁵ Centre for Tuberculosis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁶ KwaZulu-Natal Research Innovation, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁷ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁸ National Institute for Communicable Diseases, Sandringham, South Africa.
¹⁹ School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
²⁰ Department of Pathology, Cape Town, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Witwatersrand, South Africa; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
²¹ Hutchinson Center Research Institute of South Africa (HCRISA), Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.
²² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
²³ Metro Health Services, Western Cape Government Health, Cape Town, South Africa; Division of Health Systems and Public Health, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
²⁴ National Department of Health, Pretoria, South Africa.
²⁵ South African Medical Research Council, Tygerberg, South Africa.
²⁶ South Africa Medical Research Council, Cape Town, South Africa.
²⁷ University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Cape Town, South Africa.
²⁸ Division of Clinical Haematology, Department of Medicine, Cape Town, South Africa; Groote Schuur Hospital, Cape Town, South Africa.
²⁹ Faculty of Health Sciences, and Allergy and Immunology Unit, Cape Town, South Africa.
³⁰ Neurology Association of South Africa, The Southern African Society of Thrombosis and Haemostasis, Johannesburg, South Africa.
³¹ Division of Allergy and Clinical Immunology, Cape Town, South Africa.
³² Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Witwatersrand, South Africa.
³³ School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁵ South Africa Medical Research Council, Cape Town, South Africa. Electronic address: glenda.gray@mrc.ac.za.

PMID: 35305740
PMCID: PMC8930006
DOI: 10.1016/S0140-6736(22)00007-1

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.

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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.

Figures

**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**
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).

See this image and copyright information in PMC

Comment in

Sisonke: reaching several goals together.
Preiser W, Fish T. Preiser W, et al. Lancet. 2022 Mar 19;399(10330):1095-1097. doi: 10.1016/S0140-6736(22)00482-2. Lancet. 2022. PMID: 35305727 Free PMC article. No abstract available.

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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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

MeSH terms

Substances

Supplementary concepts

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous