Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa | medRxiv preprints (not peer reviewed)

Type Journal Article Author Shabir A. Madhi Author Vicky Baillie Author Clare L. Cutland Author Merryn Voysey Author Anthonet L. Koen Author Lee Fairlie Author Sherman D. Padayachee Author Keertan Dheda Author Shaun L. Barnabas Author Qasim Ebrahim Bhorat Author Carmen Briner Author Gaurav Kwatra Author NGS-SA Author Wits-VIDA COVID Team Author Khatija Ahmed Author Parvinder Aley Author Sutika Bhikha Author Jinal N. Bhiman Author As’ad Ebrahim Bhorat Author Jeanine du Plessis Author Aliasgar Esmail Author Marisa Groenewald Author Elizea Horne Author Shi-Hsia Hwa Author Aylin Jose Author Teresa Lambe Author Matt Laubscher Author Mookho Malahleha Author Masebole Masenya Author Mduduzi Masilela Author Shakeel McKenzie Author Kgaogelo Molapo Author Andrew Moultrie Author Suzette Oelofse Author Faeezah Patel Author Sureshnee Pillay Author Sarah Rhead Author Hylton Rodel Author Lindie Rossouw Author Carol Taoushanis Author Houriiyah Tegally Author Asha Thombrayil Author Samuel van Eck Author Constantinos Kurt Wibmer Author Nicholas M. Durham Author Elizabeth J. Kelly Author Tonya L. Villafana Author Sarah Gilbert Author Andrew J. Pollard Author Tulio de Oliveira Author Penny L. Moore Author Alex Sigal Author Alane Izu URL https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1 Rights © 2021, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/ Pages 2021.02.10.21251247 Publication medRxiv Date 12/02/2021 Extra Publisher: Cold Spring Harbor Laboratory Press DOI 10.1101/2021.02.10.21251247 Library Catalog www.medrxiv.org Language en Abstract Background Assessing 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. Methods We 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. Results 2026 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. Conclusions A 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).