Barry Schoub | The ABC of AstraZeneca vaccine and the B.1.351 variant

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SA has sold its batch of AstraZeneca vaccines to the AU.
SA has sold its batch of AstraZeneca vaccines to the AU.
PHOTO: Justin Tallis/AFP

The overriding reason for suspending the rollout of the AstraZeneca vaccine is that South Africa is virtually the only country in the world almost totally dominated by the immune-resistant SARS CoV-2 virus variant, writes Barry Schoub.

The decision by the government to suspend the rollout of one million doses of the AstraZeneca [AZ] vaccine, which arrived in South Africa in February, still elicits some considerable unease in the public, and even in some professional circles.

The science underlying the advice given to the Department of Health by the Ministerial Advisory Committee on Vaccines can be viewed at three levels:

A]  A one sentence explanation.

B]  A four-sentence explanation or

C]  A fuller scientific background.

Dominated by 501Y.V2 or B.1.351

A] In one sentence – the fundamental and overriding reason for suspending the rollout of the AZ vaccine is the fact that South Africa is virtually the only country in the world almost totally dominated by the immune-resistant SARS CoV-2 virus variant, termed 501Y.V2 or B.1.351.

B] Essentially, there are four pieces of supportive scientific evidence for the advisory:

1. The level of neutralising antibodies produced following AZ vaccination is significantly lower than that produced by other vaccines, such as the Pfizer vaccine.

2. Laboratory studies demonstrated that AZ-elicited antibodies had little or no ability to neutralise the B.1.351 variant virus.

3. Corresponding to the laboratory findings, the clinical trials conducted in South Africa similarly showed that the efficacy to prevent clinical illness dropped from about 60% in overseas studies down to 21.9% in South Africa. And, in a smaller B.1.351 subgroup, the efficacy dropped even further to only 10.4%.

4. The efficacy of the vaccine to prevent severe disease and hospitalisation, the most important outcome, could not be assessed as, unfortunately, the South African trial excluded the all-important age group of over 65 years of age.

Role of neutralising antibodies 

C] For a fuller scientific background, let us first examine the role of neutralising antibodies in immune defence. It is true that the precise laboratory correlates of immune protection are still not entirely clear. The immune system is indeed complex, and functionally it is certainly broader than neutralising antibodies alone. Undoubtedly cellular immunity, non-neutralising antibodies, as well as innate immunity, all contribute to immune protection.

Nevertheless, neutralising antibodies have long been a useful and reliable metric of protection against virus infection. (An exception are those viruses which cause latent infections and often reactivate in the presence of neutralising antibodies, e.g. viruses of the herpes family and HIV. However, there is no evidence that SARS CoV-2 virus undergoes latent infection).

Therefore, the virtual absence of effective AZ vaccine-elicited antibodies against B.1.351 must be a serious signal of the impotence of the AZ vaccine against the variant virus.

READ | Explainer: Key insights from US trial data on AstraZeneca's Covid-19 vaccine

Corroborating these laboratory studies, clinical trial results published recently [16th March] in the prestigious peer-reviewed journal, the New England Journal of Medicine, revealed the poor ability of AZ to prevent mild-to-moderate illness due to B.1.351.

Despite these findings, there is still speculation in some quarters that the other components of the immune system may somehow play a role in hypothetically protecting against severe disease due to B.1.351. Unfortunately, there is currently no evidence to support this speculation.

There is also the claim that because the AZ vaccine is structured similarly to other adenovirus-vectored vaccines, such as Johnson and Johnson [J&J], which is proven to be effective against B.1.351, AZ should function as well. This is incorrect.

While J&J uses a human adenovirus vector, AZ use a non-human, chimpanzee, adenovirus vector.

It is well-established that adenoviruses are effective vaccine vectors, which play an important role in the presentation of the viral antigen to the immune system.

However, there may well be differences how different adenovirus species assist in the priming of the immune system. Furthermore, the structure of the virus insert, i.e. that piece of the virus' genome incorporated into the vector, which elicits the specific immune response, is different in the two vaccines. These differences may well account for the much more efficient immune response to the B.1.351 variant by J&J vaccine, as compared to AZ.

Any downsides?

Over and above these scientific reasons, there were also important societal reasons.

The argument has been made: "Why not make the vaccine available to those volunteers who wish to take the chance that it may possibly still be effective in preventing severe disease by the variant, especially given the current tardiness of the vaccine programme in the healthcare worker implementation study?"

Bottom line: Was there a downside to at least giving AZ a try? Was there anything to lose?

I believe there are three important downsides to "giving it a try", and one important medical ethical downside.

Firstly, if the vaccine will not work to prevent severe disease, and, as we have seen, there certainly are some worryingly compelling pieces of evidence that it may not work, it could engender false confidence and false security in those vaccine recipients.

READ | Covid-19: Sale of AstraZeneca vaccine to AU concluded - Health Minister Zweli Mkhize

Secondly, the all-important population confidence and societal trust in vaccines could be seriously damaged by manifestly visible vaccine failures.

Thirdly, utilising short supply consumables, such as the global shortage in syringes, and other limited resources, such human vaccinators, for a vaccine which may or may not work, is clearly not justifiable.

Finally, medical interventions, be it drugs, procedures or vaccines, must be founded on authentic scientific evidence.

Obviously, should there be no other alternative, experimental interventions of unknown efficacy may well be justifiable in medical practice.

Constantly changing 

However, in South Africa at the current time, there is no credible scientific evidence that the AZ vaccine would prevent severe disease. The only available evidence suggests that it may well not be effective. While, on the other hand, there are alternative vaccines available, where there is scientific evidence of efficacy against the variant, even if there has to be a relatively short wait for it.

It goes without saying that our knowledge of Covid-19 and our planned responses to the pandemic are constantly changing.

Should the AZ vaccine be demonstrated in the future to be satisfactorily effective against B.1.351 or other future variants, it may well occupy an important public health role in South Africa. However, public health interventions must continue to be guided by the best, currently available, scientific evidence.

Barry Schoub is the Chair of the Ministerial Advisory Committee on Covid Vaccines. He was the founding Director of the National Institute for Communicable Diseases and is Professor Emeritus of Virology, University of the Witwatersrand. He has written this piece in his personal capacity.

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