Clinical Trial

. 2023 May 26;41(23):3486-3492.

doi: 10.1016/j.vaccine.2023.04.058. Epub 2023 Apr 27.

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005)

Anthonet L Koen¹, Alane Izu¹, Vicky Baillie¹, Gaurav Kwatra², Clare L Cutland³, Lee Fairlie⁴, Sherman D Padayachee⁵, Keertan Dheda⁶, Shaun L Barnabas⁷, Qasim Ebrahim Bhorat⁸, Carmen Briner⁹, Khatija Ahmed¹⁰, Sutika Bhikha¹, Jinal N Bhiman¹¹, Jeanine du Plessis¹, Aliasgar Esmail¹², Elizea Horne⁴, Shi-Hsia Hwa¹³, Aylin Oommen-Jose¹, Teresa Lambe¹⁴, Matt Laubscher¹, Mookho Malahleha¹⁵, Gabriella Benade⁴, Shakeel McKenzie¹, Suzette Oelofse¹², Faeezah Patel⁴, Sureshnee Pillay¹⁶, Sarah Rhead¹⁷, Hylton Rodel¹³, Carol Taoushanis¹, Houriiyah Tegally¹⁶, Asha Thombrayil¹, Tonya L Villafana¹⁸, Sarah Gilbert¹⁹, Andrew J Pollard²⁰, Shabir A Madhi²¹

Affiliations

¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Clinical Microbiology, Christian Medical College, Vellore, India.
³ African Leadership in Vaccinology Expertise (ALIVE), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Setshaba Research Centre, Tshwane, South Africa.
⁶ Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, South Africa.
⁷ Family Centre for Research with Ubuntu, Department of Paediatrics, Stellenbosch University, Cape Town, South Africa.
⁸ Soweto Clinical Trials Centre, Soweto, South Africa.
⁹ Perinatal HIV Research Unit, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Setshaba Research Centre, Tshwane, South Africa; Faculty of Health Sciences, Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
¹¹ National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa; SAMRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
¹² Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, Cape Town, South Africa.
¹³ Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, UK.
¹⁴ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK; Chinese Academy of Medical Science, Oxford Institute, University of Oxford, Oxford, UK.
¹⁵ Setshaba Research Centre, Tshwane, South Africa; Synergy Biomed Research Institute, East London, Eastern Cape, South Africa.
¹⁶ KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Centre for Epidemic Response and Innovation (CERI), Stellenbosch University, Stellenbosch, South Africa.
¹⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK.
¹⁸ Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
¹⁹ Nuffield Department of Medicine, University of Oxford, ORCRB, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
²⁰ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
²¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: shabir.madhi@wits.ac.za.

PMID: 37149443
PMCID: PMC10133888
DOI: 10.1016/j.vaccine.2023.04.058

Clinical Trial

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005)

Anthonet L Koen et al. Vaccine. 2023.

. 2023 May 26;41(23):3486-3492.

doi: 10.1016/j.vaccine.2023.04.058. Epub 2023 Apr 27.

Authors

Affiliations

¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Clinical Microbiology, Christian Medical College, Vellore, India.
³ African Leadership in Vaccinology Expertise (ALIVE), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Setshaba Research Centre, Tshwane, South Africa.
⁶ Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, South Africa.
⁷ Family Centre for Research with Ubuntu, Department of Paediatrics, Stellenbosch University, Cape Town, South Africa.
⁸ Soweto Clinical Trials Centre, Soweto, South Africa.
⁹ Perinatal HIV Research Unit, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Setshaba Research Centre, Tshwane, South Africa; Faculty of Health Sciences, Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
¹¹ National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa; SAMRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
¹² Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, Cape Town, South Africa.
¹³ Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, UK.
¹⁴ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK; Chinese Academy of Medical Science, Oxford Institute, University of Oxford, Oxford, UK.
¹⁵ Setshaba Research Centre, Tshwane, South Africa; Synergy Biomed Research Institute, East London, Eastern Cape, South Africa.
¹⁶ KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Centre for Epidemic Response and Innovation (CERI), Stellenbosch University, Stellenbosch, South Africa.
¹⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK.
¹⁸ Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
¹⁹ Nuffield Department of Medicine, University of Oxford, ORCRB, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
²⁰ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
²¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: shabir.madhi@wits.ac.za.

PMID: 37149443
PMCID: PMC10133888
DOI: 10.1016/j.vaccine.2023.04.058

Abstract

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa's Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674.

Keywords: AZD1222; COVID-19; ChAdOx1 nCov-19; SARS-CoV-2 variant; Vaccine efficacy.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shabir Madhi reports financial support was provided by GlaxoSmithKline. Shabir Madhi reports financial support was provided by AstraZeneca. Shabir Madhi reports financial support was provided by BMGF. Shabir Madhi reports financial support was provided by South African Medical Research Council. Shabir Madhi reports financial support was provided by Pfizer. Shabir Madhi reports financial support was provided by Minervax. Shabir Madhi reports financial support was provided by Novavax. Shabir Madhi reports financial support was provided by Providence. Shabir Madhi reports financial support was provided by Greenstone. Shabir Madhi reports financial support was provided by ImmunityBio. Clare L. Cutland reports financial support was provided by BMGF. Clare L. Cutland reports financial support was provided by Pfizer. Clare L. Cutland reports financial support was provided by Biovac. Lee Fairlie reports financial support was provided by South African Medical Research Council. Lee Fairlie reports financial support was provided by Bill and Melinda Gates Foundation. Mookho Malahleha reports financial support was provided by Synergy Biomed Research Institute. Andrew J. Pollard reports financial support was provided by University of Oxford. Andrew J. Pollard reports financial support was provided by Shionogi. Andrew J. Pollard reports financial support was provided by AstraZeneca. Andrew J. Pollard reports financial support was provided by National Institute for Health and Care Research. Qasim Ebrahim Bhorat reports financial support was provided by Wits Health Consortium. Qasim Ebrahim Bhorat reports financial support was provided by Regeneron Pharmaceuticals. Qasim Ebrahim Bhorat reports financial support was provided by GlaxoSmithKline. Qasim Ebrahim Bhorat reports financial support was provided by Avillion. Qasim Ebrahim Bhorat reports financial support was provided by Sanofi. Qasim Ebrahim Bhorat reports financial support was provided by NovoNordisk. Qasim Ebrahim Bhorat reports financial support was provided by Bill & Melinda Gates Foundation. Qasim Ebrahim Bhorat reports financial support was provided by South African Medical Research Council. Qasim Ebrahim Bhorat reports financial support was provided by Novavax. Qasim Ebrahim Bhorat reports financial support was provided by AstraZeneca. Qasim Ebrahim Bhorat reports financial support was provided by Clover BioPharmaceticals. Tonya L. Villafana reports financial support was provided by AstraZeneca. Clare L. Cutland reports a relationship with BMGF that includes: employment and funding grants. Mookho Malahleha reports a relationship with RTI that includes: consulting or advisory. Andrew J. Pollard reports a relationship with UK Joint Committee on Vaccines and Immunization that includes: board membership. Andrew J. Pollard reports a relationship with World Health Organisation SAGE that includes: board membership. Sarah Gilbert reports a relationship with Vaccitech that includes: equity or stocks. Teresa Lambe reports a relationship with Vaccitech that includes: consulting or advisory. Mookho Malahleha reports a relationship with Synergy Biomed Research Institute that includes: board membership, employment, and equity or stocks. Sarah Gilbert has patent issued to Vaccitech. Teresa Lambe has patent issued to Vaccitech.

Figures

**Fig. 1**
Participant disposition. ^aUpdated from enrollment reported in , to exclude five participants who were randomized but withdrew before they received their first injection.

**Fig. 2**
Rolling mean number of total monthly SARS-CoV-2 infections through time. The color indicates the rolling mean of prevalence out of all samples for Alpha (light blue), Beta (green), Delta (dark blue) and unclassified (gray). The unclassified isolates were detected in individuals with viral loads too low (>32Ct) to get a definite strain classification. Abbreviation: Ct, Cycle threshold. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 3**
Cumulative incidence over time for any SARS-CoV-2 infection (including both asymptomatic and symptomatic illness) due to wild type (a), Beta (b) and Delta (c) variants, and overall (d).

See this image and copyright information in PMC

References

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Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005)

Affiliations

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005)

Authors

Affiliations

Abstract

Conflict of interest statement

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Supplementary concepts

Associated data

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