Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa

Madhi, Shabir A.; Baillie, Vicky L.; Cutland, Clare; Voysey, Merryn; Al, Koen; Fairlie, Lee; Sd, Padayachee; Dheda, Keertan; Sl, Barnabas; Qe, Bhorat; Briner, Carmen; Kwatra, Gaurav; Ahmed, Khatija; Aley, Parvinder K.; Bhikha, Sutika; Jn, Bhiman; Ae, Bhorat; Jd, Plessis; Esmail, Aliasgar; Groenewald, M.; Horne, Elizea; S, Hwa; Jose, Aylin; Lambe, Teresa; Laubscher, Marius; Malahleha, Mookho; Masenya, Maysseb; Masilela, Mduduzi; McKenzie, Shakeel; Molapo, K; Moultrie, Andrew; Oelofse, Suzette; Patel, Faeezah; Pillay, Sureshnee; Rhead, Sarah; Rodel, Hylton; Rossouw, Lindie; Taoushanis, Carol; Tegally, Houriiyah; Thombrayil, Asha; Sv, Eck; Wibmer, Constantinos Kurt; Durham, NM; Ej, Kelly; Tl, Villafana; Gilbert, Sarah C.; Aj, Pollard; Oliveira, Túlio de; Pl, Moore; Sigal, Alex; A, Izu

doi:10.1101/2021.02.10.21251247

Cited by 99 publications

(111 citation statements)

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“…48 Preliminary data suggest that, in common with other ancestral spikebased vaccines, ChAdOx1 nCov-19 might have a lower clinical efficacy against upper respiratory infection caused by viral lineages bearing this mutation. 49 Further work is ongoing to ascertain the impact of E484K on the neutralising activity and efficacy afforded by ChAdOx1 nCov-19. Preclinical COVID-19 vaccine studies suggest that the development of neutralising antibody is associated with protection from subsequent challenge with live virus.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Emary¹,

Golubchik²,

Aley³

et al. 2021

The Lancet

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Background A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. Methods Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 − relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov , NCT04400838 , and ISRCTN, 15281137. Findings Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18–55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2–11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6–84·5) for B.1.1.7 and 81·5% (67·9–89·4) for non-B.1.1.7 lineages. Interpretation ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. Funding UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

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Section: Discussionmentioning

confidence: 99%

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Emary¹,

Golubchik²,

Aley³

et al. 2021

The Lancet

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599

509

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“…This is an interim analysis of the continuing, adaptive, phase 1b/2, double-blind, randomized, placebo-controlled COV005 trial, assessing the safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in South Africa, details of which have previously been published 9 . Brie y, the trial began enrolling on June 24, 2020, and is being carried out in 7 South African locations in accordance with principles of the Declaration of Helsinki and Good Clinical Practice Guidelines 7 .…”

Section: Clinical Trial Design and Trial Participantsmentioning

confidence: 99%

ChAdOx1 nCoV-19 (AZD1222) Vaccine in People Living With and Without HIV

Madhi

Koen

Fairlie

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern1. People living with HIV (PLWH) are at increased risk for adverse COVID-19 outcomes compared with HIV-negative individuals2-5, and are a high-risk group for COVID-19 prevention4. The ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated safety and efficacy against COVID-19 in clinical trials6-8. To date, there are no reports on the safety and immunogenicity of this, or any COVID-19 vaccine, in PLWH, and reports on the immunogenicity of COVID-19 vaccines in Africa are limited9. Here, we show comparable safety and immunogenicity of two doses of ChAdOx1 nCoV-19 between PLWH and HIV-negative individuals in South Africa. Furthermore, in PLWH previously exposed to SARS-CoV-2, antibody responses increased substantially from baseline following a priming dose, with modest increases after a booster dose. Full-length spike and receptor-binding domain IgG geometric mean concentrations after a single dose of ChAdOx1 nCoV-19 in PLWH previously exposed to SARS-CoV-2 were 6.49–6.84-fold higher than after two doses in those who were SARS-CoV-2 naïve at enrollment. Neutralizing antibody responses were consistent with the antibody-binding responses. This is the first report of a COVID-19 vaccine specific to PLWH, and specific to Africa, and demonstrates favorable safety and immunogenicity of ChAdOx1 nCoV-19 in PLWH.

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“…The identification of a correlate of protection is too important and urgent 3 and reductions in neutralising activity in vaccinee serum samples for all four vaccines tested. [4][5][6][7] Although these reductions were small for the BBIBP-CorV, 4 BNT162b2, 5 and mRNA-1273 6 vaccines, preliminary data suggest they were substantial, including with a complete immune escape for the AZD1222 vaccine. 7 Concerningly, the clinical trial efficacy of AZD1222 was 70% in the UK and Brazil, 8 but 22% according to preliminary data from South Africa.…”

mentioning

confidence: 93%

“…[4][5][6][7] Although these reductions were small for the BBIBP-CorV, 4 BNT162b2, 5 and mRNA-1273 6 vaccines, preliminary data suggest they were substantial, including with a complete immune escape for the AZD1222 vaccine. 7 Concerningly, the clinical trial efficacy of AZD1222 was 70% in the UK and Brazil, 8 but 22% according to preliminary data from South Africa. 7 For NVX-CoV237 the efficacy was 89% in the UK but Gender-neutral policy making inherently neglects the needs of women.…”

mentioning

confidence: 93%

“…7 Concerningly, the clinical trial efficacy of AZD1222 was 70% in the UK and Brazil, 8 but 22% according to preliminary data from South Africa. 7 For NVX-CoV237 the efficacy was 89% in the UK but Gender-neutral policy making inherently neglects the needs of women. 3 Thus, it is imperative to ensure that all considerations of health-care workers are disaggregated by gender and race to understand the differential effect between different members of the workforce.…”

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confidence: 99%

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