A few journalists have asked us about comments made by Pascal Soriot, the Executive Director and Chief Executive Officer of AstraZeneca, during an interview on BBC Radio 4’s The Today Programme this morning.
Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:
“I am aware of at least one relatively small study that showed antibody levels in older people, a few weeks after their second dose of vaccine, were greater in those receiving mRNA vaccine whilst T cells were nearly 50% greater in those receiving the AZ vaccine (https://immunityageing.biomedcentral.com/articles/10.1186/s12979-021-00246-9). But this needs to be looked at in the context of the wealth of literature and real-life data.
“Real-life data for vaccine effectiveness suggests that the Pfizer vaccine out-performs the AZ vaccine in protecting against infection and symptomatic infection, but both vaccines are still delivering good, and reasonably comparable, protection from serious disease.
“I think the real reason we are seeing stable case numbers here in the UK and escalating numbers in many parts of the EU is more to do with levels of population immunity. In the UK we have been seeing high virus circulation when we came out of lockdown in summer, and that has generated relatively high levels of immunity in younger people. Most older people have gained immunity from vaccination. That was not the case in some EU countries.
“This means that our population is generally less susceptible to infection and serious disease. And this resistance has been bolstered by booster vaccination. But immunity doesn’t last forever. It’s important to get vaccinate or boosted, even if you have already been infected with the virus. High levels of immunity in our population will put the brakes on virus spread and disease.”
Dr Lance Turtle, Senior Clinical Lecturer and Consultant Physician in Infectious Diseases, University of Liverpool, NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, said:
“Clinical trials and real-world experience show that the Oxford Astra Zeneca vaccine provides excellent protection against severe disease and death from COVID-19. There is also some information on the relative effectiveness of the AZ vaccine compared with other vaccines. However, these are observations that are not well controlled for all the other factors that might affect whether people get sick from COVID-19. No clinical trial has properly assessed the effectiveness of AZ vaccine and other vaccines side by side. This would be the only way to be sure that one vaccine was really more effective than another.
“The ComCOV study compared giving either a dose of AZ followed by Pfizer, or the other way round, or only AZ or only Pfizer vaccines. This study looked at lab measures of how well the vaccine worked, rather than actual cases of COVID-19. Antibodies were higher with the Pfizer vaccine. T cells, a specialised set of white blood cells, were also measured. The ComCOV study showed that the T cell response to the AZ vaccine was slightly larger than the T cell response to the Pfizer vaccine after one dose. But when a second dose was given 28 days later, the response after the second dose was similar between the two vaccines.
“Several other studies have also found T cell responses after both the AZ and Pfizer vaccines. It is possible that a longer time after vaccination the AZ vaccine turns out to have better T cell responses, but we do not know this yet. Future studies will be needed to tell if this is the case.
“At the moment, it is not possible to say for certain whether the AZ COVID-19 vaccine is better than any other vaccine. Based on the real-world experience this is unlikely to be the case. If it is the case the difference will probably be small.
“There are many reasons why the infection rate, the hospitalisation rate and the death rate may vary between countries. These include how many people have been vaccinated, and when they were vaccinated. The appearance of variants can have an effect, especially if they appear a long time after people have been vaccinated. The age of the population and the prevalence of other diseases will have an effect. Drawing comparisons between countries presents many difficulties, and is very likely to lead to conclusions which are not reliable.
“All the COVID-19 vaccines available in the UK are excellent at protecting against needing hospital treatment or dying from COVID-19. They achieve as good an immune response as natural infection. When combined with natural infection, they provide even higher protection. it is really important to get vaccinated to protect yourself against COVID-19. It is important to have two doses of vaccine, and to get a third dose as well if you are in group who is offered it. Even if you have had COVID-19, you should still have all doses offered, as the body’s response is even better still. It is much less important to worry about which vaccine you get. The best COVID-19 vaccine you can get is the one you can get the soonest.”
Prof Matthew Snape, Associate Professor in Paediatrics and Vaccinology, University of Oxford, and Chief Investigator of the Com-COV trial, said:
“Useful data regarding T cell responses come from the COMCOV study, a randomised trial in which we compared antibody and T cell responses in those receiving ‘standard’ or ‘mixed’ schedules of the COVID-19 vaccines manufactured by Pfizer and AstraZeneca. The Lancet publication of this can be read here: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01694-9/fulltext
“These showed that, while a single dose of the AZ vaccine does induce a better T cell response than the Pfizer mRNA vaccine, shortly after 2 doses the T cell response was very similar. We are following up these studies to look at what these responses look like up to 6 months after the second dose.
“Intriguingly, the best T cell responses seem to come if you give a first dose of the AZ vaccine followed by Pfizer, and using vaccines across different platforms to optimise T cell responses is an important avenue to explore to help generate the most effective vaccine responses.”
Prof Eleanor Riley, Professor of Immunology and Infectious Disease, The University of Edinburgh, said:
“It does seem, from a growing number of clinical trials, that the mRNA vaccines initially induce higher levels of neutralising antibodies than the Oxford AZ vaccine and that these antibodies persist somewhat longer after the second vaccination. As these antibodies are particularly important for preventing initial infection by the virus, this likely explains why protection against infection is slightly higher – and lasts slightly longer – after mRNA vaccination.
“However, it also seems that the Oxford AZ vaccine initially induces higher levels of T cells than the mRNA vaccines. These T cells are important for long term immune memory and also for inhibiting virus replication and killing infected cells once an infection becomes established. T cells are therefore assumed to contribute to long term protection against severe COVID-19. Since the AZ vaccine is slightly better at inducing these T cells, the implication is that it may provide longer term protection against hospitalisation and death. I think this is the point that Dr Soriot was making.
“However, getting good data on this is complicated. The different vaccines have been rolled out at different times and in different groups of people with different underlying risks of severe disease, making direct comparison between them very difficult. Moreover, the virus has changed over time since the first vaccines were deployed (with Delta being much more infectious and more able to evade vaccine-induced antibodies) and now the boosters are being rolled out, with everyone – in the UK at least – being offered an mRNA booster whichever vaccine they had first time around. So, any differences between the types of vaccine will be even harder to detect.
“In practice, unless they turn out to be very large, any differences in long term efficacy between the vaccines are unlikely to be the major driver of vaccine choice. Differences in cost, in availability, and in ease of storage, transportation and administration, are more likely to influence the choice of vaccine in any particular setting.”
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, Chair of the BMA Public Health Medicine Committee until October 2020, said:
“I am not aware of the specific evidence that Pascal Soriot was referring to, but I might be able to provide some background.
“If you’ll excuse the cliché, immunology is not rocket science – it’s much harder!
“There are many different aspects to the immune system – and to how it prevents, fights, or causes disease. Any classification of it is likely to be a simplification but (just as all models are wrong but some are useful), they can help us to understand what is going on.
“One way of classifying the immune system is into “adaptive” and “innate”, with the adaptive part of the immune system relating to the response once the immune system has learned to respond to a particular threat – and that’s what we’re dealing with, with vaccination.
“The adaptive immune system can be divided into “humoral” and “cellular”. “Humoral” immunity refers to the immunity found in the blood, or specifically, serum, the non-cellular part of the blood – ie, to antibodies. And cellular immunity is all the rest. Humoral immunity is relatively easy to measure – you can relatively easily assess how much of a particular kind of antibody is in a serum sample. Measuring cellular immune responses in the laboratory is much more tricky, so we tend to see a lot of reports of antibody levels following disease or vaccination, and fewer reports on cellular immunity.
“While B-cells (derived in the Bone marrow) are mostly associated with the production of antibodies, many different types of T-cells (derived in the Thymus) are involved. They include, for example, the “killer T-cells”, whose role is to kill cells which are misbehaving – including, for example, by having become vaccine factories after being infected. They are also involved with stimulating some B cells to become long-lived “memory B-cells”; cells which circulate in the bloodstream or live in the bone marrow, and which can very rapidly pump out large quantities of antibody if the virus is (or, more accurately, the relevant antigens are) detected in the future.
“Circulating antibodies (humoral immunity) can neutralise a pathogen before it can get into and infect cells. T-cells come into their own once cells have been infected.
“This means that whether people get symptomatic or serious illness, and whether and how quickly they recover, can depend on the T-cell response.
“Different vaccines can stimulate different parts of the immune system more or less effectively. It is perfectly plausible that some vaccines will stimulate a stronger T-cell response than others.
“What would this mean in the real world?
“People whose immune systems have produced a strong T-cell response, but a weaker antibody response, might (compared to somebody with a good antibody response but a poorer T-cell response) be more likely to be infected in the first place (less protection from antibodies); but more likely to be able to fight the infection so they may have no or few symptoms, and they will be much less likely to develop severe disease.
“Soriot’s commented on the fact that, while we have a high infection rate in the UK, we have a relatively low hospitalisation and death rate.
“It is plausible that this is because many people received the AstraZeneca vaccine, and this generated an excellent T-cell response, which means that while people can still be infected (and infectious), they are unlikely to be seriously unwell.
“I would be very interested to see the evidence on which this claim is based.”
Pascal Soriot interview from: 1:30:27 at this link: https://www.bbc.co.uk/sounds/play/m0011sf5
All our previous output on this subject can be seen at this weblink:
Prof Jonathan Ball: “Receiving funding to develop and trial new generation COVID19 vaccines.”
Dr Lance Turtle: “Lance Turtle received a fee for his university from Eisai for a talk on cancer and COVID-19.”
Prof Eleanor Riley: “No conflicts of interest to declare.”
Prof Matthew Snape: “MS is the Director of the National Immunisation Schedule Evaluation Consortium (NISEC) and the Chief Investigator on COMCOV, COMCOV2and COMCOV3 studies He is also an Investigator on the Oxford/AZ UK vaccine studies. He is, or has recently been, an investigator on studies funded by vaccine manufacturers including Novavax, Pfizer, GSK, MCM vaccines and Janssen.”
Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position. While he is also a member of the BMA’s Public Health Medicine Committee (and its chair until Oct 2020), this comment is made in a personal capacity. Dr English sometimes receives honoraria for acting as a consultant to various vaccine manufacturers, most recently to Seqirus.”
None others received.