The news this week continues to be dominated by concerns over the South African variant of the COVID-19 virus and concomitant stories about the possibility that the AstraZeneca vaccine will not be effective against it.
Previous blog topics have discussed some of these issues before. Click here to read "Africa - Second waves, Vaccines and Variants" and here to read "Vaccines and Variants - is there a problem?"
Once again the media is running frightening headlines such as "AstraZeneca vaccine doesn't stop South African strain" and "New Variant in South Africa renders AstraZeneca vaccine ineffective in young people." (1) (2)
South Africa suspended its plans to roll out the AZ vaccine in light of the news whilst more data could be gathered. (3)
How Significant is the South African variant?
It is important to remember that thousands of variants are in circulation around the world - this is how viruses behave. Viruses change every few weeks and whilst these changes are expected they are unpredictable in terms of exactly what aspect of the virus will change. Most variants have such minor changes from the original virus that they are insignificant and viruses can even mutate to become weaker but a few will have more marked changes and become "variants of concern".
Variants of concern are labelled as such because they may prove more infectious and/or more lethal. They may also go unrecognised by the body's immune system, so called “escape mutants”, which means a vaccine that worked pre-mutation is no longer as effective. However, if the vaccine continues to prevent serious disease and death, perhaps by reducing the illness to a milder form, that would still be hugely beneficial.
The variant identified in South Africa is known as B1351 and has some subtle but important changes to the spike protein projections on the surface of the virus. These are the target area for all of the vaccines (not just AstraZeneca's) which is why concerns have been raised.
When a variant has changes that benefit it, it can quickly dominate and become the main one in circulation. This is exactly what happened in the UK in December 2020 when the so-called UK variant of concern was first identified and quickly swept through the country. (Click here to read more on the background of the UK variant.)
New variants of concern have arisen in South Africa with B.1351 and also in Brazil which has a circulating variant now labelled B.11248.
(For ease of understanding I will continue to label these variants by country rather than by their numbered names.)
All of these variants, the UK, Brazilian and South African, have a change that is present in all three. This shared mutation seems to increase the transmission of the virus, in other words they are more infectious.
The Brazilian and South African variants also share a similar second change and there is some early evidence that this second change is beginning in the UK variant. This change may interfere with the body's immune response to the vaccine.
The fact that virtually identical changes are occurring with the virus across three different continents suggests that the virus is behaving in a similar way around the world. This at least means that a vaccine adapted to work better against one variant should also have some impact against the others.
Some scientists think the UK variant will become the world's dominant strain. It is already the main variant in the northern hemisphere and with all the current vaccines being highly effective against we should see the case and death figures for COVID-19 substantially reduce over the first half of 2021. Unfortunately this may mean the South African and Brazilian variants become dominant and the concern then is that people could potentially be re-infected by these strains if the initial vaccines don't offer any protection against them. (4)
However all is not lost as previous vaccination may still offer some protection against the South African and Brazilian variants. Despite the negative headlines there is no evidence that the current vaccines will have no effect at all on these other variants.
What exactly did the study on the AstraZeneca vaccine and the South African variant show?
The study behind the headlines is a new study that involved only 2000 people with a mean age of 31 years. The study could not establish if the vaccine was preventing severe disease and hospitalisation from the South African variant of COVID-19 because the study was too small and it was only carried out on young and healthy adults.
There were no cases of serious disease in the vaccinated group but there is not enough data to know if that was because the vaccine stopped serious disease and those infected were only mildly ill instead or if the lack of serious disease cases simply represents the fact that the study demographic was far less likely to become seriously ill anyway.
It is also of note that the first and second doses of the vaccine were given four weeks apart despite evidence which shows a longer interval gives a better immune response. (5)
So is the AZ vaccine preventing serious disease and yet not mild disease? Or is it "converting" serious disease to mild disease? It would be unusual for any vaccine to prevent the more serious cases of an infection whilst having no impact on the milder cases. It is more likely it is reducing the severity of the disease - but we do not yet have the hard data on that for the impact of the AZ vaccine on the South African variant in the way we do for the UK variant where it is proven to work.
So, what can we know for certain at this stage?
Professor Sarah Gilbert who heads up the Oxford-AstraZeneca vaccine team expects the vaccine to still protect against severe disease. Work is already underway to modify the AZ vaccine against the South Africa variant with the aim of increasing its efficacy against it.
Two vaccines which are waiting to be approved, the Janssen and Novavax vaccines, showed that whilst they were effective against all current variants, they too were less effective against the South African variant. However once again there were no hospitalisations or deaths among those in the vaccinated arms of their trials. (6) (7)
Pfizer have announced that early studies in the laboratory show their vaccine is effective against the South African variant. However laboratory findings are not always replicated in humans and they are yet to carry out trials in people. (8)
Moderna has said that its vaccine is effective against the UK variant but gives less protection against the South African one and is currently developing a booster shot to address this. (9)
The AZ vaccine creates the same neutralising antibodies as all these other vaccines. This is why scientists are confident it too will still have some effect on the South African variant. (10)
The human body's complex and multi-layered immune responses means it is highly unlikely that any single variant will be able to achieve a complete immune escape. All the current approved vaccines are likely to remain capable of both limiting infection and crucially preventing serious illness and deaths.
What has the World Health Organisation said?
The World Health Organization (WHO) and health officials around the world have backed the AZ vaccine. The WHO has recommended its use in adults of all ages and as two doses given eight to 12 weeks apart. Joachim Hombach from the WHO said, “You can expect to see a higher efficacy if you administer the vaccine in our recommended schedule which is eight to 12 weeks between doses.”
With regard to the South African variant he announced that the AZ vaccine should, "still prevent severe disease and death caused by the variant." (11)
Elsewhere, Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations, said "It is vastly too early to be dismissing this vaccine."
Professor Salim Abdool Karim, co-chair of South Africa's Ministerial Advisory Committee on COVID-19, said "It is too early to conclude that the AstraZeneca would not prevent serious disease caused by the variant prevalent there."
Prof Shabir Madhi, the lead investigator on the South African AstraZeneca trial told Reuters, "The vaccine has a major role to play in Africa and globally, and the 1 million doses in South Africa, which expire in April, should be rolled out quickly, not wasted." (12) (13)
In Conclusion
Whenever a news article says a vaccine is "ineffective" or "failing to protect" it is important to ask, "What was the end point the failure is based on?"
There are many different layers of protection - protection from death, protection from severe disease, protection from mild disease, protection from asymptomatic infection.
A vaccine that "fails" to prevent asymptomatic and mild illness but protects against serious disease and deaths is not, in my opinion, a failure.
(1) https://www.webmd.com/vaccines/covid-19-vaccine/news/20210208/astrazeneca-vaccine-doesnt-stop-south-african-strain
(2) https://nationalpost.com/news/world/new-variant-in-south-africa-renders-astrazeneca-vaccine-ineffective-in-young-people
(3) https://www.bbc.co.uk/news/world-africa-55999678
(4) https://www.bbc.co.uk/news/uk-56019995
(5) https://www.ft.com/content/e9bbd4fe-e6bf-4383-bfd3-be64140a3f36
(6) https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial
(7) https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3
(8) https://www.pfizer.com/news/press-release/press-release-detail/vitro-studies-demonstrate-pfizer-and-biontech-covid-19
(9) https://www.modernatx.com/
(10) https://www.bbc.co.uk/news/uk-55967767
(11) https://www.pmlive.com/pharma_news/who_backs_azoxford_covid-19_vaccine,_including_in_older_adults_1363151
(12) https://www.bbc.co.uk/news/world-africa-55999678
(13) https://www.reuters.com/article/us-health-coronavirus-britain/global-health-officials-back-astrazeneca-vaccine-after-south-africa-study-rings-alarm-idUSKBN2A80ME
