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; Alane Izu; Vicky Baillie; Gaurav Kwatra; Clare L Cutland; Lee Fairlie; Sherman D Padayachee; Keertan Dheda; Shaun L Barnabas; Qasim Ebrahim Bhorat; Carmen Briner; Khatija Ahmed; Sutika Bhikha; Jinal N Bhiman; Jeanine du Plessis; Aliasgar Esmail; Elizea Horne; Shi-Hsia Hwa; Aylin Oommen-Jose; Teresa Lambe; Matt Laubscher; Mookho Malahleha; Gabriella Benade; Shakeel McKenzie; Suzette Oelofse; Faeezah Patel; Sureshnee Pillay; Sarah Rhead; Hylton Rodel; Carol Taoushanis; Houriiyah Tegally; Asha Thombrayil; Tonya L Villafana; Sarah Gilbert; Andrew J Pollard; Shabir A Madhi

doi:10.1016/j.vaccine.2023.04.058

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)

Vaccine. 2023 May 26;41(23):3486-3492. doi: 10.1016/j.vaccine.2023.04.058. Epub 2023 Apr 27.

Authors

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.

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.

Publication types

Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase II
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
ChAdOx1 nCoV-19*
Humans
SARS-CoV-2 / genetics
South Africa
Vaccination

Substances

ChAdOx1 nCoV-19
COVID-19 Vaccines

Supplementary concepts

SARS-CoV-2 variants

Associated data

ClinicalTrials.gov/NCT04444674