TY - JOUR
T1 - Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study)
T2 - results from a single-arm, open-label, phase 3B, implementation study
AU - Sisonke Protocol Team
AU - Sisonke Study Team
AU - Bekker, Linda Gail
AU - Garrett, Nigel
AU - Goga, Ameena
AU - Fairall, Lara
AU - Reddy, Tarylee
AU - Yende-Zuma, Nonhlanhla
AU - Kassanjee, Reshma
AU - Collie, Shirley
AU - Sanne, Ian
AU - Boulle, Andrew
AU - Seocharan, Ishen
AU - Engelbrecht, Imke
AU - Davies, Mary Ann
AU - Champion, Jared
AU - Chen, Tommy
AU - Bennett, Sarah
AU - Mametja, Selaelo
AU - Semenya, Mabatlo
AU - Moultrie, Harry
AU - de Oliveira, Tulio
AU - Lessells, Richard John
AU - Cohen, Cheryl
AU - Jassat, Waasila
AU - Groome, Michelle
AU - Von Gottberg, Anne
AU - Le Roux, Engelbert
AU - Khuto, Kentse
AU - Barouch, Dan
AU - Mahomed, Hassan
AU - Wolmarans, Milani
AU - Rousseau, Petro
AU - Bradshaw, Debbie
AU - Mulder, Michelle
AU - Opie, Jessica
AU - Louw, Vernon
AU - Jacobson, Barry
AU - Rowji, Pradeep
AU - Peter, Jonny G.
AU - Takalani, Azwi
AU - Odhiambo, Jackline
AU - Mayat, Fatima
AU - Takuva, Simbarashe
AU - Corey, Lawrence
AU - Gray, Glenda E.
AU - Brumskine, William
AU - Naicker, Nivashnee
AU - Makhaza, Disebo
AU - Naicker, Vimla
AU - Naidoo, Logashvari
AU - Nchabeleng, Maphoshane
N1 - Funding Information:
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.
Funding Information:
We thank the health-care workers who participated in the Sisonke study. We thank the clinical research site investigators, the study staff and teams, and the support staff at the SAMRC. We thank the data and analytical teams at Discovery Health and Government Employees Medical Scheme, Medscheme, and the provincial public health teams at Western Cape Government Health. In particular, we thank Steven Dorfman, Naomi Folb, Stanley Moloabi, and Theuns Jacobs. We also thank Paul Stoffels, Johan van Hoof, and Abeda Williams from Janssen, Johnson & Johnson, who facilitated and provided the investigational product. We thank the President of South Africa, Cyril Ramaphosa and the previous Minister of Health, Zweli Mkhize for their support. We thank Sandile Buthelezi, Anban Pillay, Lesley Bamford, Gaurang Tanna, Khadija Jamaloodien, and the National Department of Health, and the nine Provincial Departments of Health, vaccination sites, and staff. We are also grateful for the support of the private medical clinics for partnering with Sisonke and establishing vaccination sites. We thank the Biovac Institute for vaccine storage and packing, Biocair South Africa and Leonard Lazarus for the distribution of the vaccines, and the National Joint Operational Intelligence Structure for ensuring safe deployment. We also thank Zameer Brey, Koleka Mlisana, Rob Botha, Penny Moore, Peter Gilbert, and Holly Janes. We also thank the SAMRC for their unfailing support. The Sisonke Safety Desk were critical to support the pharmacovigilance of the study. We also thank the Hutchinson Cancer Research Institute of South Africa staff for their hard work in providing training and oversight of study operations. We thank Right to Care for their expansion in the rural areas of the Northern Cape and Eastern Cape with the assistance of Josef Tayag and Thomas Minior, United States Agency for International Development (grant number AID-OAA-A-15-00070). We also thank our regulator, South African Health Products Regulatory Authority, and the Health Research Ethics Committees who provided guidance and oversight. Direct funding for the Sisonke study was provided by the 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 (grant number 21-V0001), and the Bill & Melinda Gates Foundation (grant number INV-030342). The content is solely the responsibility of the authors and does not necessarily represent the official views of Johnson & Johnson or our funders. The funders had an opportunity to review a preliminary version of the manuscript; however, the authors are solely responsible for the final content and interpretation.
Funding Information:
We thank the health-care workers who participated in the Sisonke study. We thank the clinical research site investigators, the study staff and teams, and the support staff at the SAMRC. We thank the data and analytical teams at Discovery Health and Government Employees Medical Scheme, Medscheme, and the provincial public health teams at Western Cape Government Health. In particular, we thank Steven Dorfman, Naomi Folb, Stanley Moloabi, and Theuns Jacobs. We also thank Paul Stoffels, Johan van Hoof, and Abeda Williams from Janssen, Johnson & Johnson, who facilitated and provided the investigational product. We thank the President of South Africa, Cyril Ramaphosa and the previous Minister of Health, Zweli Mkhize for their support. We thank Sandile Buthelezi, Anban Pillay, Lesley Bamford, Gaurang Tanna, Khadija Jamaloodien, and the National Department of Health, and the nine Provincial Departments of Health, vaccination sites, and staff. We are also grateful for the support of the private medical clinics for partnering with Sisonke and establishing vaccination sites. We thank the Biovac Institute for vaccine storage and packing, Biocair South Africa and Leonard Lazarus for the distribution of the vaccines, and the National Joint Operational Intelligence Structure for ensuring safe deployment. We also thank Zameer Brey, Koleka Mlisana, Rob Botha, Penny Moore, Peter Gilbert, and Holly Janes. We also thank the SAMRC for their unfailing support. The Sisonke Safety Desk were critical to support the pharmacovigilance of the study. We also thank the Hutchinson Cancer Research Institute of South Africa staff for their hard work in providing training and oversight of study operations. We thank Right to Care for their expansion in the rural areas of the Northern Cape and Eastern Cape with the assistance of Josef Tayag and Thomas Minior, United States Agency for International Development (grant number AID-OAA-A-15-00070). We also thank our regulator, South African Health Products Regulatory Authority, and the Health Research Ethics Committees who provided guidance and oversight. Direct funding for the Sisonke study was provided by the 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 (grant number 21-V0001), and the Bill & Melinda Gates Foundation (grant number INV-030342). The content is solely the responsibility of the authors and does not necessarily represent the official views of Johnson & Johnson or our funders. The funders had an opportunity to review a preliminary version of the manuscript; however, the authors are solely responsible for the final content and interpretation.
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2022/3/19
Y1 - 2022/3/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126537263&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(22)00007-1
DO - 10.1016/S0140-6736(22)00007-1
M3 - Article
C2 - 35305740
AN - SCOPUS:85126537263
SN - 0140-6736
VL - 399
SP - 1141
EP - 1153
JO - The Lancet
JF - The Lancet
IS - 10330
ER -