Review 2: "Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa"

Julian Ruiz-Saenz

doi:doi:10.1162/2e3983f5.b070ec70

This preprint suggests the Astra-Zeneca vaccine had little efficacy against non-hospitalized mild to moderate Covid-19 due to B.1.351. Reviewers found it was potentially informative, suggesting the need for more studies to assess vaccine effectiveness against the B.1.351 variant.

by Julian Ruiz-Saenz

Published onApr 20, 2021

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

by Shabir A. Madhi, Vicky Baillie, Clare L. Cutland, Merryn Voysey, Anthonet L. Koen, Lee Fairlie, Sherman D. Padayachee, Keertan Dheda, Shaun L. Barnabas, Qasim Ebrahim Bhorat, Carmen Briner, Gaurav Kwatra, Khatija Ahmed, Parvinder Aley, Sutika Bhikha, Jinal N. Bhiman, As’ad Ebrahim Bhorat, Jeanine du Plessis, Aliasgar Esmail, Marisa Groenewald, Elizea Horne, Shi-Hsia Hwa, Aylin Jose, Teresa Lambe, Matt Laubscher, Mookho Malahleha, Masebole Masenya, Mduduzi Masilela, Shakeel McKenzie, Kgaogelo Molapo, Andrew Moultrie, Suzette Oelofse, Faeezah Patel, Sureshnee Pillay, Sarah Rhead, Hylton Rodel, Lindie Rossouw, Carol Taoushanis, Houriiyah Tegally, Asha Thombrayil, Samuel van Eck, Constantinos Kurt Wibmer, Nicholas M. Durham, Elizabeth J Kelly, Tonya L Villafana, Sarah Gilbert, Andrew J Pollard, Tulio de Oliveira, Penny L. Moore, Alex Sigal, Alane Izu, undefined undefined, and undefined undefined

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AbstractBackgroundAssessing safety and efficacy of Covid-19 vaccines in different populations is essential, as is investigation of efficacy against emerging SARS-CoV-2 variants of concern including the B.1.351 (501Y.V2) variant first identified in South Africa.MethodsWe conducted a randomized multicentre, double blinded controlled trial on safety and efficacy of ChAdOx1-nCoV19 in HIV-uninfected people in South Africa. Participants age 18 to <65 years randomized (1:1) to two doses of vaccine containing 5×1010 viral particles or placebo (0.9%NaCl) 21-35 days apart. Post 2nd-dose serum samples (n=25) were tested by pseudotyped (PSVNA) and live virus (LVNA) neutralization assays against the D614G and B.1.351 variants. Primary endpoints were safety and vaccine efficacy (VE) >14 days following second dose against laboratory confirmed symptomatic Covid-19.Results2026 HIV-uninfected adults were enrolled between June 24th and Nov 9th, 2020; 1010 and 1011 received at least one dose of placebo or vaccine, respectively. Median age was 31 years. The B.1.351 variant showed increased resistance to vaccinee sera using the PSVNA and LVNA. In the primary endpoint analysis, 23/717 (3.2%) placebo and 19/750 (2.5%) vaccine recipients developed mild-moderate Covid-19; VE 21.9% (95%Confidence Interval: −49.9; 59.8). Of the primary endpoint cases, 39/42 (92.9%) were the B.1.351 variant; against which VE was 10.4% (95%CI: −76.8; 54.8) analyzed as a secondary objective. The incidence of serious adverse events was balanced between the vaccine and placebo groups.ConclusionsA two-dose regimen of ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, VE against severe Covid-19 is undetermined.(Funded by The Bill & Melinda Gates Foundation and South African Medical Research Council; ClinicalTrails.gov number, NCT04444674).

RR:C19 Evidence Scale rating by reviewer:

Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

The paper by Madhi et al., entitled Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa explored an important problem that the COVID-19 vaccine is facing at this time.

The paper has multiple strengths mainly because the authors conducted a randomized multicenter, double-blinded controlled trial. In general, the results are well-presented, however, some mistakes must be corrected such as the lack of figure 1. For this reviewer, it is not appropriate to include data from other cohorts for the shared analyzes, as presented in figure 2.

The safety results of the ChAdOx1-nCoV vaccine are very promising and show that it can be applied without risk to the population. Additionally, the absence of reactogenicity was observed after the 2nd dose.

The appropriate evaluation of T-helper lymphocyte cell responses is really important to perform an adequate analysis in the South African vaccinee population since the data included in the paper belongs to a different cohort from another country (unpublished data on a subset of 17 ChAdOx1-nCoV-19 recipients from the UK).

For this reviewer, it is very important that the paper shows that ChAdOx1-nCoV had no efficacy against non-hospitalized mild to moderate Covid-19 mainly due to the B.1.351 variant. The lack of efficacy being specific to the B.1.351 variant, is supported by primary/secondary outcomes and by PSVNA and LVNA.

The conclusion of the paper adequately reflects the results presented.

Review 2: "Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa"

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