South Africa suspends use of AstraZeneca vaccine

 

South Africa has suspended use of the Oxford-AstraZeneca vaccine in its vaccination drive after a small clinical trial suggested that the drug is not effective in preventing mild to moderate illness from the variant dominant in the country.

South Africa's Minister of Health Dr Zweli Mkhize Sunday said the halt would be temporary while the government awaited advice from scientists on how best to proceed. In the meantime, Dr Mkhize said South Africa will move forward with the deployment of vaccines made by Pfizer/BioNTech and Johnson & Johnson.

The developments, coming nearly a week after the arrival of a million doses of the AstraZeneca-Oxford vaccine might have an enormous setback for a country like Kenya which is heavily relying on the same vaccine and doesn’t have a variety of options to choose from. Kenya is one of the countries expecting a shipment of 4.2million doses from the Covid-19 Vaccines Global Access (Covax) facility later this month.

But the country has some advantages so far. For starters, there have only been three confirmed cases of the new variant, with the latest reported in a truck driver detected in Lunga Lunga in Kwale County following sequencing of 60 samples early this year.

According to acting director-general for health Patrick Amoth, test results of contacts of the said driver have since turned negative and therefore there was no evidence the two strains are active in Kenya. Dr Amoth said even though the B.1.351 (also called the 501Y.V2) variant, predominant in South Africa, is more transmissible, Kenya has not recorded any upsurge of cases, which so far stand at 101,819.

For Dr Moses Masika, a virologist at the University of Nairobi, despite the low numbers, there is need to confirm how far the variant might have spread beyond the three cases. Kenya Medical Research Institute had planned to sequence 400 samples between January and February in multiple sites across the country to ascertain the extent of the spread of new variants. Results of this data are yet to be announced.

“My concern is that we have not characterised the strains circulating locally very well. The number we have sequenced so far is very small, about 500 out of more than 100,000 cases. We should sequence more genomes to know which strains are here and whether any of them poses a problem,” said Dr Masika, adding that for now, “I would not strike it [the vaccine] out of the list for Kenya yet, since we do not have any evidence to support such a decision,” he explained.

In an analysis, submitted as a pre-print prior to peer-review publication, a two-dose regimen of the AstraZeneca vaccine known as ChAdOx1 nCoV-19 provided minimal protection against mild to moderate infection caused by 501Y.V2 coronavirus variant first identified in South Africa in mid-November 2020.

Clinical trial data are important for the drug and medical device development processing pharmaceutical companies to examine and evaluate the efficacy and safety of the new medical product in human volunteers. This data is a staple resource for most health and medical research and is either collected during the course of ongoing patient care or as part of a formal clinical trial program.

Prior to widespread circulation of the variant found to be more contagious, the vaccine was found to be about 75 per cent effective, researchers said.

However, in a later analysis based mostly on infections caused by the new variant, there was only a 22 per cent lower risk of developing mild-to-moderate Covid-19 compared to those given a placebo. Although researchers said the figure was not statistically significant, due to trial design, it is well below the benchmark of at least 50 per cent regulators have set for vaccines to be considered effective against the virus.

Professor Shabir Madhi, the principal investigator on the AstraZeneca trial, said data on the vaccine were a reality check and that it was time to “recalibrate our expectations of COVID-19 vaccines”.

 “When researchers looked at protection that the AstraZeneca jab provided against mild to moderate Covid19 disease, there was considerable protection against the original form of the virus. But the antibodies induced by the jab didn't work nearly as well for 501Y.V2,” he said.

Pro Madhi also said that there is some evidence from the Novavax vaccine trial that showed that people with natural immunity against the original form of Sars-CoV-2 (the virus that causes Covid-19), are not protected against getting infected with 501Y.V2.

“We don't yet know if the AstraZeneca vaccine will protect  against severe Covid-19 causes by 501Y.V2. All we know is that it doesn't protect against mild to moderate Covid-19 caused by the new variant,” said Prof Madhi during his presentation at the conference.

Until the end of October 2020 (before the variant emerged), the protection conferred by the AstraZeneca vaccine provided similar levels of protection in the UK, SA and Brazil. The scientists said that they believed the vaccine might protect against more severe cases, based on the immune responses detected in blood samples from people who were given the jab. If further studies show that to be the case, South African health officials will consider resuming use of the AstraZeneca-Oxford vaccine, they said.

The number of cases evaluated as part of the studies outlined by South African scientists on Sunday were low, making it difficult to pinpoint just how effective or not the vaccine might be against the variant. The 2,000 evaluated clinical trial participants were also relatively young (18-65 years) and unlikely to become severely ill. Therefore, it was impossible for the scientists to determine if the variant interfered with the AstraZeneca-Oxford vaccine’s ability to protect against severe Covid-19, hospitalisations or deaths.

“The only Covid-19 vaccine that we have clinical data for that protects against severe Covid-19 caused by the new variant 501Y.V2, is the Johnson & Johnson vaccine,” said Salim Abdool Karim, an epidemiologist and co-chair of the South African Ministerial Advisory Committee on Covid-19.

Mutations in the spike protein of the 501Y.V2 (or B.1.351) may, in theory, reduce, but not obliterate the recognition of the virus by antibodies (the body’s defense mechanism against infections). This is because, in practice, the human immune system will recognise more than a single region of the spike protein. These mutations may reduce vaccine efficacy directed against the spike protein.

Currently, most Covid-19 vaccines specifically target the spike protein. There are also some like ones developed by China which uses an inactivated virus that targets a wider array of viral proteins, inducing several protective immune responses. But this kind instils redundancy in the protective immune responses.

Until now, there has been insufficient indication that mutations recorded in the 501Y.V2 variant affect the function of drugs. Early results from  Pfizer-BioNTech and Moderna suggest their vaccine is still effective against the South Africa variant, while AstraZeneca has said its vaccine provides good protection against the variant first identified in the UK.