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Durability of ChAdOx1 nCoV-19 (AZD1222) Vaccine and Hybrid Humoral Immunity Against Variants Including Omicron BA.1 and BA.4 Six Months after Vaccination: A Randomised, Phase 1b/2a Trial

30 Pages Posted: 28 Jul 2022

See all articles by Shabir A. Madhi

Shabir A. Madhi

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Gaurav Kwatra

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Richard Welch

National Institute For Communicable Diseases Of South Africa - Division of Public Health Surveillance and Response

Anthonet L. Koen

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Vicky L. Baillie

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Clare Cutland

University of the Witwatersrand - Faculty of Health Sciences

Lee Fairlie

University of the Witwatersrand - Reproductive Health and HIV Research Unit (RHRU)

Sherman D. Padayachee

Setshaba Research Centre

Keertan Dheda

University of Cape Town (UCT) - Centre for Lung Infection and Immunity

Shaun L. Barnabas

Soweto Clinical Trials Centre; Stellenbosch University - Family Centre for Research with Ubuntu

Qasim Ebrahim Bhorat

Soweto Clinical Trials Centre

Carmen Briner

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Khatija Ahmed

Setshaba Research Centre

Parvinder K. Aley

University of Oxford - Centre for Vaccinology and Tropical Medicine

Sutika Bhikha

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

As'ad Ebrahim Bhorat

Soweto Clinical Trials Centre

Aliasgar Esmail

University of Cape Town (UCT) - Centre for Lung Infection and Immunity

Elizea Horne

University of the Witwatersrand

Haajira Kaldine

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases

Christian K. Mukendi

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Vimbai Sharon Madzorera

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases

Nelia P. Manamela

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases

Mduduzi Masilela

Setshaba Research Centre

Tandile Hermanus

National Institute for Communicable Diseases of the National Health Laboratory Service

Thopisang Motlou

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases

Nonkululeko Mzindle

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases

Suzette Oelofse

University of Cape Town (UCT) - Centre for Lung Infection and Immunity

Faeezah Patel

University of the Witwatersrand

Sarah Rhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection; University of Oxford - Centre for Vaccinology and Tropical Medicine

Lindie Rossouw

University of the Witwatersrand - Reproductive Health and HIV Research Unit (RHRU)

Carol Taoushanis

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Samuel van Eck

University of the Witwatersrand

Teresa Lambe

University of Oxford - Centre for Vaccinology and Tropical Medicine

Sarah C. Gilbert

University of Oxford - The Jenner Institute

Andrew J. Pollard

University of Oxford - Centre for Vaccinology and Tropical Medicine

Penny L. Moore

University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa

Alane Izu

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

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Abstract

Background: Covid-19 vaccine rollout is lagging in Africa, where there has been a high force of SARS-CoV-2 infection. We evaluated the effect of SARS-CoV-2 infection prior to vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days (D180).

Methods: We undertook a post-hoc immunogenicity analysis after two doses of AZD1222 in a randomised, placebo-controlled phase Ib/2a study undertaken in South Africa.  Recipients were stratified by serological assessment of SARS-CoV-2 infection prior to 1st dose into baseline seropositive or baseline seronegative groups. Binding immunoglobulin G (IgG) to spike (anti-S) and receptor binding domain (anti-RBD) were measured prior to first dose (D0),  2nd dose (D28), and at D42 and D180. Neutralizing antibody (NAb) against SARS-CoV-2 variants D614G, Beta, Delta, Gamma, A.VOI.V2, Omicron BA1 and BA.4 variants and SARS-CoV-1, were measured by pseudovirus assay (D28, D42 and D180). Antibody dependent cellular cytoxicity against D614G and Delta was measured at D28 and D42.

Findings: Anti-S (and anti-RBD) IgG geometric mean concentrations (GMCs) were higher throughout in the baseline seropositive than seronegative group, persisting to D180 (GMCs: 517.8 vs 82.1 BAU/ml). Similarly, the percentage who had anti-S IgG ≥264BAU/ml (i.e. putative 80% risk reduction threshold [PRRT] against wild type (WT)/Alpha symptomatic Covid-19) was 76.6% vs 13.8% at D180.  Also D614G NAb geometric mean titres (GMT) were higher in the baseline seropositive than seronegative group, as was the percentage with titres ≥185 (80% PRRT against WT/Alpha Covid-19) even at D180 (92.0% vs 18.2%). Similar findings were observed for Beta, A.VOI.V2 and Gamma at D28, D42 and D180. NAb GMTS against BA.1 and BA.4 were higher in the baseline seropositive than seronegative group at D28 (499 vs. 14; and 436 vs. 25.0) and D42 (535 vs. 16; and 429 vs. 25.0), as was the percentage with NAb titres ≥185 for BA.1 and BA.4 at D28 (84.0% and 87.5% vs. 0%) and D42 (84.0% and 87.5% vs. 0%).  

Interpretation: A single dose of AZD1222 in the general African population, where Covid-19 vaccine coverage is low and SARS-CoV-2 seropositivity is 90%, could enhance the magnitude and quality of antibody responses to SARS-CoV-2.

Trial Registration Details: The COV005 study is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinical Trials Registry, ACTR202006922165132.

Funding Information: Grants from The Bill & Melinda Gates Foundation and the South African Medical Research Council provided funding for the study and the funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Vaccines used in the study were donated by the University of Oxford.

Declaration of Interests: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). SCG is cofounder of Vaccitech, a collaborator in the early development of this vaccine candidate, and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine (GB2003670.3). TL is named as an inventor on a patent application covering ChAdOx1 nCoV-19 and was a consultant to Vaccitech. All other authors declare no competing interests.

Ethical Approval Statement: The study was approved by the South African Health and Pharmaceutical Products Regulatory Authority (SAHPRA) and the Human Ethics Research Committees of the various sites. Signed informed consent was obtained from all study participants. The South African Health Products Regulatory Authority (SAHPRA, reference 20200407), the Ethics committees at the University of the Witwatersrand, (HREC:200501), University of Stellenbosch (Ref: M20/06/009_Covid-19), University of Cape Town (Ref: 350/2020) and Oxford Tropical Research Ethics Committee (OxTREC ref 35-20) at the University of Oxford provided Ethics approval.

Keywords: COVID-19, AZD1222, immunogenicity, durability of protection

Suggested Citation

Madhi, Shabir A. and Kwatra, Gaurav and Welch, Richard and Koen, Anthonet L. and Baillie, Vicky L. and Cutland, Clare and Fairlie, Lee and Padayachee, Sherman D. and Dheda, Keertan and Barnabas, Shaun L. and Bhorat, Qasim Ebrahim and Briner, Carmen and Ahmed, Khatija and Aley, Parvinder K. and Bhikha, Sutika and Bhorat, As'ad Ebrahim and Esmail, Aliasgar and Horne, Elizea and Kaldine, Haajira and Mukendi, Christian K. and Madzorera, Vimbai Sharon and Manamela, Nelia P. and Masilela, Mduduzi and Hermanus, Tandile and Motlou, Thopisang and Mzindle, Nonkululeko and Oelofse, Suzette and Patel, Faeezah and Rhead, Sarah and Rossouw, Lindie and Taoushanis, Carol and van Eck, Samuel and Lambe, Teresa and Gilbert, Sarah C. and Pollard, Andrew J. and Moore, Penny L. and Izu, Alane, Durability of ChAdOx1 nCoV-19 (AZD1222) Vaccine and Hybrid Humoral Immunity Against Variants Including Omicron BA.1 and BA.4 Six Months after Vaccination: A Randomised, Phase 1b/2a Trial. Available at SSRN: https://ssrn.com/abstract=4173050 or http://dx.doi.org/10.2139/ssrn.4173050

Shabir A. Madhi (Contact Author)

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit ( email )

Gaurav Kwatra

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit ( email )

Richard Welch

National Institute For Communicable Diseases Of South Africa - Division of Public Health Surveillance and Response ( email )

South Africa

Anthonet L. Koen

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Vicky L. Baillie

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Clare Cutland

University of the Witwatersrand - Faculty of Health Sciences ( email )

7 York Rd
Parktown, Johannesburg 2193
South Africa

Lee Fairlie

University of the Witwatersrand - Reproductive Health and HIV Research Unit (RHRU) ( email )

Sherman D. Padayachee

Setshaba Research Centre

Soshanguve
South Africa

Keertan Dheda

University of Cape Town (UCT) - Centre for Lung Infection and Immunity ( email )

Cape Town
South Africa

Shaun L. Barnabas

Soweto Clinical Trials Centre ( email )

Stellenbosch University - Family Centre for Research with Ubuntu ( email )

Qasim Ebrahim Bhorat

Soweto Clinical Trials Centre ( email )

Carmen Briner

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Khatija Ahmed

Setshaba Research Centre

Soshanguve
South Africa

Parvinder K. Aley

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Sutika Bhikha

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit ( email )

As'ad Ebrahim Bhorat

Soweto Clinical Trials Centre ( email )

Aliasgar Esmail

University of Cape Town (UCT) - Centre for Lung Infection and Immunity ( email )

Cape Town
South Africa

Elizea Horne

University of the Witwatersrand

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Haajira Kaldine

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases ( email )

Johannesburg
South Africa

Christian K. Mukendi

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Vimbai Sharon Madzorera

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases ( email )

Johannesburg
South Africa

Nelia P. Manamela

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases ( email )

Johannesburg
South Africa

Mduduzi Masilela

Setshaba Research Centre

Soshanguve
South Africa

Tandile Hermanus

National Institute for Communicable Diseases of the National Health Laboratory Service ( email )

South Africa

Thopisang Motlou

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases ( email )

Johannesburg
South Africa

Nonkululeko Mzindle

National Health Laboratory Services (NHLS) - National Institute for Communicable Diseases ( email )

Johannesburg
South Africa

Suzette Oelofse

University of Cape Town (UCT) - Centre for Lung Infection and Immunity ( email )

Cape Town
South Africa

Faeezah Patel

University of the Witwatersrand

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Sarah Rhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Lindie Rossouw

University of the Witwatersrand - Reproductive Health and HIV Research Unit (RHRU) ( email )

Carol Taoushanis

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Samuel Van Eck

University of the Witwatersrand

1 Jan Smuts Avenue
Johannesburg, GA 2000
South Africa

Teresa Lambe

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Sarah C. Gilbert

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Andrew J. Pollard

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Penny L. Moore

University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa ( email )

Durban
South Africa

Alane Izu

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit ( email )

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