South Africa Pauses AstraZeneca Vaccine Rollout Over Small but Dismal Study Results

 

South Africa has delayed the distribution of the AstraZeneca-University of Oxford COVID-19 vaccine after data suggested it “provides minimal protection” against mild disease from the South African variant. The data was announced by the Wits Vaccines and Infectious Diseases Analytics (VIDA) Research Unit, which is running the COVID-19 vaccine trial in South Africa. The data has yet to be peer-reviewed.

Actual efficacy against severe COVID-19 infection for the South African variant was not evaluated, but the vaccine had high efficacy against the original non-B.1.351 variants in South Africa. The study suggests that AstraZeneca-Oxford vaccine neutralized the virus, but that the B.1.351 variant was significantly decreased compared to the original, “wildtype” variant that originated in China.

The study evaluated about 2,000 volunteers, mostly young, with a median age of 31 years. Mild disease was defined as at least one symptom of COVID-19. Because of the low-risk target population, they could not evaluate efficacy against moderately severe disease, hospitalization or death.

The University of Oxford and AstraZeneca are already working on a next-generation vaccine that is modified for the South African B.1.351 variant, if necessary.

“Recent data from a study in South Africa sponsored by Janssen which assessed moderate to severe disease, rather than mild disease, using a similar viral vector, indicated that protection against these important disease endpoints was preserved,” said Shabir Madhi, professor of Vaccinology and director of VIDA at the University of the Witwatersrand, and chief investigator of the South Africa trial. “This could be relevant to the ChAdOx1 nCoV-19 vaccine [the AstraZeneca-Oxford vaccine], which has been developed using similar technology as the Janssen vaccine, and for which vaccine induced immune responses are also similar.”

He added, “These findings also force us to recalibrate thinking about how to approach the pandemic virus and shift the focus from the aspirational goal of herd immunity against transmission to the protection of all at risk individuals in population against severe disease.”

Two virologists who are advising the South African government said during a press conference that the country’s rollout-pause was necessary so the government could develop a new process to try and determine that each vaccine decreases COVID-19 vaccinations in the country.

“The AstraZeneca vaccine rollout needs to be put on a temporary halt while we get the clinical efficacy information in,” stated Salim Abdool Karim, an epidemiologist at Columbia University and a participant in a commission that is advising the South African government. “And the way that we can do that is with the new approach to rollout.”

The news adds fuel to the fire over concerns about the South African variant, B.1.351. The AstraZeneca-Oxford vaccine has not been authorized for use in the U.S. and seems unlikely to be for several months, if then. It has been granted authorization in the U.K. and European Union, but has not yet been submitted for authorization in the U.S. In the U.K., South Africa and Brazil, the vaccine demonstrated 76% efficacy after a single dose, which rose to 82% after a second dose three months later.

The U.S. Food and Drug Administration (FDA) is waiting for a U.S. clinical trial to be completed. AstraZeneca indicated that it thinks the trial will wrap in “the next month or two.”

The delay is at least partially related to a clinical hold that occurred in November 2020 after a U.K. patient suffered a partial paralysis of the spine that may have been related to the vaccine. Although the clinical trials resumed quickly afterwards in the U.K. and other countries, such as Brazil, it was delayed for several weeks in the U.S. while the FDA evaluated the data.

There were also other questions about the AstraZeneca-Oxford data. A cohort of the trial accidentally received half-doses of the initial shot, and that group demonstrated efficacy up to 90%, while the full-dose group had an efficacy of 62%. That difference has yet to be explained. There are also questions about how well the vaccine works in people over 65.

Ashish Jha, dean of the Brown University School of Public Health, said it is “a reasonable decision under normal circumstances” for the FDA to wait for “cleaner” data from the U.S. clinical trial, although he added, “there’s a reasonable question to ask: Are these normal circumstances?”

According to the company, data from the Phase III U.K. trial has already been shared with the FDA, and as soon as U.S. trial data is available, it will be submitted as well. Regulators in Germany and France have indicated there is not sufficient data to justify authorizing the vaccine in people over the age of 65, and as a result, have only authorized it for people below that age.

An early look at the study data behind the South African pause does not give a clear picture of the issue. The data is only in a small number of patients and may be insufficient for a conclusion.

Madhi noted that before B.1.351 became more common in South Africa, the AstraZeneca-Oxford vaccine was trending toward decreasing mild COVID-19 cases by 75%. But as the variant emerged, that number dropped significantly, and cases were decreased only 22% based on 42 cases of symptomatic COVID-19. However, that data isn’t viewed as reliable, with the confidence interval for the 22% figure ranging from -50% to 60%.

AstraZeneca, for its part, believes the vaccine will still protect against severe disease with the South African variant and that the current study doesn’t provide information about that.