{"id":3851,"date":"2021-03-17T09:57:07","date_gmt":"2021-03-17T07:57:07","guid":{"rendered":"https:\/\/wits-vida.org\/?p=3851"},"modified":"2022-03-25T10:00:28","modified_gmt":"2022-03-25T08:00:28","slug":"findings-of-the-sa-study-in-the-oxford-astrazeneca-covid-19-vaccine-trial-have-been-published-in-the-new-england-journal-of-medicine-nejm","status":"publish","type":"post","link":"https:\/\/wits-vida.org\/press-release\/findings-of-the-sa-study-in-the-oxford-astrazeneca-covid-19-vaccine-trial-have-been-published-in-the-new-england-journal-of-medicine-nejm\/","title":{"rendered":"South African Oxford AstraZeneca Covid-19 vaccine study a global game-changer"},"content":{"rendered":"
\"Prof<\/span><\/div>

Findings of the SA study in the Oxford AstraZeneca Covid-19 vaccine trial have been published in the New England Journal of Medicine (NEJM).<\/strong><\/p>\n<\/div>

The\u00a0NEJM<\/em>, which\u00a0published<\/a>\u00a0the study on 16 March 2021 following peer review, is\u00a0the leading medical journal globally.<\/p>\n

This is a landmark study in so far as being the first to raise the alarm that, despite early successes with Covid-19 vaccines, further research is warranted on a next generation of Covid-19 vaccines.<\/p>\n

The results from this study, however, only indicate that the AstraZeneca vaccine does not have at least 60% efficacy against mild-moderate Covid-19 due to the B.1.351 (N501Y.V2) variant.<\/p>\n

Based on a broader body of evidence, the World Health Organization recommends that this vaccine still be deployed in countries where the B.1.351 variant circulates, as it likely still protects against severe infection, hospitalisation, and death caused by Covid-19.<\/p>\n

Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics (VIDA) Research Unit at the University of the Witwatersrand, Johannesburg, led the trial in South Africa:<\/p>\n

\u201cDespite the disappointing finding that the AstraZeneca vaccine did not protect against mild Covid infection because of the B.1.351 variant first identified in South Africa, peer review and publication of our research validates the findings and makes a compelling case for the development of a second-generation vaccines worldwide,\u201d says Madhi.<\/p>\n

First-generation vaccines refer to those designed to respond to the original SARS-CoV-2 virus. Second-generation vaccines refer to technology and design innovations that can provide protections against the constantly evolving variants that cause Covid-19 disease.<\/p>\n

A rapid response to variant reality<\/strong><\/p>\n

The findings of this study were\u00a0previously publicised<\/a>\u00a0as a preprint on Sunday, 7 February 2021, and concluded that the ChAdOx1 nCoV-19 vaccine provided minimal protection against mild to moderate Covid-19 infection from the B.1.351 coronavirus variant first identified in South Africa in mid-November 2020.<\/p>\n

Prior to the evolution of the B.1.351 and P.1 variants, the South African National Department of Health (NDOH) had ordered and taken delivery of approximately one million doses of the Oxford AstraZeneca vaccine on 1 February 2021, after a\u00a0published<\/a>\u00a0pooled analysis of this vaccine in December 2020 showed an overall vaccine efficacy of 66.7% in the UK and Brazil.<\/p>\n

\u201cWe were in a state of euphoria about the high efficacy of several Covid-19 vaccines against the original virus, but then the AstraZeneca study threw us a curve-ball,\u201d says Madhi. \u201cIn this study now published in NEJM, we found that two doses of ChAdOx1 nCoV19 had no efficacy against non-hospitalized mild to moderate Covid-19, mainly due to the B.1.351 variant.\u201d<\/p>\n

What the SA study published in\u00a0NEJM<\/em>\u00a0reveals<\/strong><\/p>\n

The randomised, multi-centre, double-blinded trial enrolled 2026 participants between 24 June and 9 November 2020.<\/p>\n

The trial was a phase 1b\/11 trial that aimed to evaluate the safety, immunogenicity, and efficacy of the AstraZeneca vaccine ChAdOx1 nCoV19 in preventing symptomatic Covid-19. Immunogenicity refers to the ability of a foreign substance, such as an antigen, to provoke an immune response. Vaccine efficacy refers to the percentage reduction of a disease in a clinical trial.<\/p>\n

\u201cA trial enrolling just 2026 participants is considered small, while phase 3 trials enroll tens of thousands of participants,\u201d says Madhi. \u201cYet the startling data that our small trial generated was irrefutable, and the implications profound.\u201d<\/p>\n

Profile of a South African AstraZenca Covid-19 vaccine trial participant<\/em><\/p>\n

The majority of participants enrolled were relatively young (under 65-years-old), generally healthy, and HIV-negative. The median [middle] age of participants was 30 years old. More than half (56.5%) of the trial participants identified as male, 70.5% were Black Africans, 12.8% were white, and 14.9% identified as \u2018mixed\u2019 race.<\/p>\n

\u201cThese demographics are important because they reflect characteristics of the overall population in South Africa. Conducting clinical trials in diverse settings like these is critical to understanding how vaccines work in local contexts,\u201d says Madhi.<\/p>\n

Testing a hypothesis<\/em><\/p>\n

The primary ojective of this trial was to establish this vaccine\u2019s efficacy against\u00a0all-severity<\/em>\u00a0Covid-19, irrespective of variants.<\/p>\n

A secondary objective was to evaluate the vaccine\u2019s efficacy against the B.1.351 variant specifically.<\/p>\n

\u201cWhen this trial began in June 2020, we were testing a vaccine against SARS-COV-2,\u201d says Madhi. \u201cBy January 2021, SARS-CoV-2 had spawned variants, including the B.1.351 first discovered in South Africa. As a secondary objective, we tested a hypothesis: would this vaccine prove at least 60% efficacious in preventing mild to moderate Covid-19 disease? It did not.\u201d<\/p>\n

The results showed that a two-dose regimen of ChAdOx1-nCov19 did not show protection against mild to moderate Covid-19 due to the B.1.351 variant.<\/p>\n

Crucially, Madhi notes that, \u201cThis vaccine may still help protect high-risk individuals with co-morbidities from contracting severe Covid-19 disease, having to be hospitalised, mechanically ventilated, or dying. The AstraZeneca vaccine remains essential in the arsenal against this virus, particularly in Africa, which has already received 14 million doses of this vaccine as the Covid-19 immunization programme starts in multiple countries.\u201d<\/p>\n

How the WHO took note<\/strong><\/p>\n

On 15 February 2021, the WHO\u00a0recommended<\/a>\u00a0that the AstraZeneca vaccine still be rolled out, even in countries where the B.1.351 variant or other similar variants of concern are circulating.<\/p>\n

A WHO news release says that the vaccine was reviewed on 8 February by the WHO Strategic Advisory Group of Experts on Immunization (SAGE), which makes recommendations for vaccines\u2019 use in populations (i.e. recommended age groups, intervals between shots, advice for specific groups such as pregnant and lactating women). The SAGE recommended the vaccine for all age groups 18 years and above.<\/p>\n

\u201cWhile the AstraZeneca vaccine \u2013 like many other first-generation Covid-19 vaccines \u2013 is unlikely to interrupt transmission of SARS-CoV-2 or protect against\u00a0mild<\/em>\u00a0infection from variants like B.1.351, these first-generation vaccines could still provide the only sustainable option to prevent flooding our hospitals with severe Covid-19 cases, and to mitigate Covid-19 deaths once the third wave hits,\u201d says Madhi.<\/p>\n

Second-generation vaccine innovation<\/strong><\/p>\n

The development of an Oxford AstraZeneca and other Covid-19 vaccines targeting the B.1351 variant is currently underway.<\/strong><\/p>\n

The South African study increased awareness worldwide of the necessity of developing vaccines that target variants specifically \u2013 and even reimagining vaccines entirely.<\/p>\n

Innovations in vaccine technologies, platforms and designs suggest exciting advances in this field.<\/p>\n

\u201cThe finding of our [Oxford AstraZeneca Covid-19 vaccine] study are truly a turning point in Covid vaccine development \u2013 and a rude awakening,\u201d says Madhi. \u201cThis one small South African study has alerted the world to the fact that second generation Covid-19 vaccines will be required to provide protection against inevitable and persistent SARS-COV-2 variants. If we had not conducted this trial in South Africa, the world would be none the wiser.\u201d<\/p>\n<\/div>