As more than a dozen countries throughout Europe have suspended use of the ChAdOx1 (Oxford-AstraZeneca) Covid-19 vaccine due to concerns that it might cause blood clots, there is more bad news regarding the vaccine — according to peer-reviewed data from South Africa, the vaccine failed to show protection against mild-to-moderate Covid-19 in people with the B.1.351 variant of the virus first identified in that country.
Of the roughly 2,000 people enrolled in the placebo-controlled trial in South Africa, 3.2% and 2.5%, respectively, in the placebo- and 2-dose ChAdOx1 Covid-19 vaccine groups developed mild-to-moderate Covid-19, and vaccine efficacy was determined to be just over 10% among people infected with the B.1.351 variant.
The study findings were published online Tuesday, March 16, in The New England Journal of Medicine.
On Monday, Germany, France, Italy, and Spain joined a growing list of European countries that have stopped administering the vaccine due to reports that blood clots had occurred in some recipients. ChAdOx1 is one of three vaccines approved for use in Europe.
There is, as yet, no proof that the blood clots that have occurred are linked to the vaccine, which has been given to millions of people in Europe. On Monday, the regulatory European Medicines Agency (EMA) announced that it would be working closely with AstraZeneca and other health authorities to investigate the reported cases.
EMA executive director Emer Cooke said in a virtual press conference that while there was no indication that the vaccine caused the blood clots, the matter would be thoroughly investigated. Cooke said the agency remains “firmly convinced that the benefits of the ChAdOx1 Covid-19 vaccine outweigh the risks and side effects.”
The B.1.351 variants of SARS-CoV-2 contains three receptor-binding domain (RBD) mutations (N501Y, E484K and K417N) as well as 5 N-terminal domain (NTD) mutations.
In a previous pooled analysis of the data from the AstraZeneca vaccine trials in the United Kingdom, Brazil, and South Africa, performed before the emergence of B.1.351, researchers reported an overall vaccine efficacy of 66.7% (95% CI, 57.4-74.0) for ChAdOx1.
In the newly published interim analysis, researchers Shabir Madhi, PhD, and colleagues reported phase Ib-II trial data from South Africa, including data on patients infected with the B.1.351 variant.
Study participants between the ages of 18 and 64 years were assigned in a 1:1 ratio to receive two doses of ChAdOx1 vaccine containing 5×1010 viral particles or placebo 21 to 35 days apart.
Serum samples obtained from 25 participants after the second dose were tested by pseudo-virus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary endpoints were vaccine safety and efficacy more than 14 days after the second dose.
Between late June and early November 2020, a total of 2,026 HIV-negative adults (median age, 30 years) were enrolled in the study and 1,010 and 1,011 participants received at least one dose of placebo or vaccine, respectively.
Both pseudo-virus and live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients compared to samples from placebo recipients.
Among the other main findings:
- In the primary endpoint analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% CI, −49.9 to 59.8).
- Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary endpoint, was 10.4% (95% CI, −76.8 to 54.8).
- The incidence of serious adverse events was balanced between the vaccine and placebo groups.
- No cases of hospitalization for severe Covid-19 occurred among the study cohort.
“The lack of efficacy against the B.1.351 variant should be considered in the context of the 75% efficacy (95% CI, 8.7-95.5) in preventing mild-to-moderate Covid-19 with onset at least 14 days after even a single dose of ChAdOx1 nCov-19 vaccine that was observed before the B.1.351 variant emerged in South Africa,” the researchers wrote.
They further noted that since efficacy against variants was a secondary, and not a primary, study endpoint, and since the study cohort had a low risk for severe Covid-19 due to young age and overall good health, “the trial findings are inconclusive with respect to whether the vaccine may protect against severe Covid-19 caused by infection with the B.1.351 variant.”
They added that given the lack of data and uncertainty regarding the efficacy of all Covid-19 vaccines against the B.1.351 variant, research directed at this variant is urgently needed.
“Although efforts to develop second-generation Covid-19 vaccines targeted against B.1.351 and P1-like variants are under way, the only Covid-19 vaccines likely to be available for most of 2021 have been formulated against the original virus,” they wrote, adding that the AstraZeneca vaccine remains “one of the most accessible of the currently authorized Covid-19 vaccines, with an expected manufacture of approximately 3 billion doses during 2021.”
Madhi and colleagues noted that it is also one of the least costly vaccines.
“Relative resistance to human neutralizing antibody responses is expected to be a feature of the pandemic coronavirus in the years ahead, as a result of pressure on the virus to select for variants that can transmit despite immunity after natural infection or vaccination,” they concluded. “Deliberations on the utility of the ChAdOx1 nCoV-19 vaccine also need to be made in the context of ongoing global spread and community transmission of the B.1.351 variant and the evolution of other SARS-CoV-2 lineages that included similar mutations.”
- In peer-reviewed data from a study in South Africa, the ChAdOx1 vaccine failed to show protection against mild-to-moderate Covid-19 in people with the B.1.351 variant first identified in that country.
- Of the roughly 2,000 people enrolled in the placebo-controlled trial in South Africa, 3.2% and 2.5%, respectively, in the placebo- and 2-dose ChAdOx1 Covid-19 vaccine groups developed mild-to-moderate Covid-19.
Salynn Boyles, Contributing Writer, BreakingMED™
This research was funded by the Bill and Melinda Gates Foundation, and others.
Corresponding researcher Madhi reported receiving grants from Bill and Melinda Gates Foundation, grants from South African Medical Research Council , grants from NIHR, during the conduct of the study; grants and personal fees from Bill and Melinda Gates Foundation, grants from Pfizer, grants from GSK, other from Novavax, outside the submitted work.
Cat ID: 31
Topic ID: 79,31,730,933,31,926,192,561,925,934
