First data from Pfizer vaccine.
The Indian Variant (now referred to as ‘Delta’) is recognised as being highly transmissible and, as a consequence, it is now the predominant variant in the UK and elsewhere. The question in many people’s minds is whether, despite the rising number of cases, those who have been fully vaccinated will still be protected against this variant. A laboratory study published this weekend in the Lancet suggested that vaccines may be less effective. This has important consequences both for individuals and communities as to how careful, despite vaccination, we need to be in returning to ‘normal’ life.
A second concern raised by this study is that the level of protection against this variant after one dose could be much less than against other variants. As vaccine roll out to younger generations is proceeding apace, how much more careful should they be with this variant? Are greater warnings needed not to relax their guard until after their second dose?
In this post I will try and explain the issues and what the new data tell us
Why we need to understand the background to these variants in relation to current vaccines?
- In order to understand why there is now a concern about vaccines and variants, we need to trace the rise and fall of the key variants
- The variants of the virus all differ in the shape of its spike protein
- Importantly they vary in the specific part of the spike protein that allows the virus to enter our cells
- The Indian variant is the most different in this respect from the Wuhan original virus
- Vaccines were developed to produce an antibody response to the spike protein and were designed specifically based on the detailed genetic code for the protein for the Wuhan variant – which was shared worldwide early on in the pandemic by the Chinese
- The hope from the vaccine developers, even though they could not know what mutations might arise, was that the spike protein of any emergent variants would not be so different that the ‘Wuhan designed vaccine’ would not still work
- However, the Indian variant is the most different in that part of the spike protein that attaches to the cells in the body, so it is less of a given how much vaccines would work against it
What does ‘how much vaccines work’ mean?
- The vaccines all aim that the body produces antibodies against the spike protein of any of the variants
- These antibodies can knock out (posh term ‘neutralise’) the virus
- This is not an all or nothing response with any of the vaccines:
- All the vaccines should produce some neutralising response
- The level of this response may vary between the different variants of the virus, as explained above
- But the vaccines are designed to be very powerful, so just because there is a lower neutralising response against some variants, this does not mean that this would not be sufficient to stop infection
- Also importantly individuals will vary in their antibody response because of:
- Health issues including obesity
- Other factors that are not known
- Plus the antibody response may wane over time
- (not discussed in this post is that – as regular readers will recall – vaccines also work by boosting our T cells to fight infection as well as antibodies – but they are much harder to study!)
What do these new Lancet data tell us:
The study addressed the following questions:
Who did they study?
- 250 health worker volunteers in London
- All had had 2 doses of the Pfizer vaccine
- Their mean age was 42, with just one quarter aged over 52
What did they test?
- The serum from these volunteers was tested for the level of ‘neutralising antibodies’ (ie antibodies that should stop the infection) at 25 days after the first and 25 and 100 days after the second vaccine dose
- Antibodies were tested in each serum sample to see if they would neutralise against the following strains of the virus:
3. UK (Alpha)
4. South African (Beta)
5. Indian (Delta)
(the Brazilian (Gamma) strain was not tested)
- They also analysed the antibody responses to compare the results by age, between men and woman and by body weight
What did they find?
- The good news was that only 3% of the participants had no antibodies against the Indian strain
- Indeed, that percentage was less than the 5% who had no antibodies against the South African strain
- But, the ability of the antibodies to neutralise the virus was different when compared between the strains
- The researchers helpfully presented their data, not just in the levels of antibodies, but more importantly in simple terms ‘how much less good was each sample at neutralising one of the variants compared to the Wuhan’
- As an analogy think of taking an antibiotic for a throat infection caused by one of 2 bacteria, ‘A’ and ‘B’. The antibiotic might have some benefit against both types of bacteria but on average be only half as effective against ‘B’ than ‘A’.
- The researchers in the Lancet study, rather than presenting such a result as ‘half as effective”, preferred to say ‘twice (twofold) as ineffective’ (hope that’s not too confusing!)
- So here are the data:
- Thus these vaccinated volunteers had weaker responses to all the strains but they were particularly weaker (nearly 6 times) against the Indian variant
- But they were also 5 times weaker against the South African variant
Were the results from all people the same?
- As you would expect, the answer is no
- Many of the volunteers actually had a good neutralising response to the Indian variant
- Others had a very weak response
- On average their response was much lower than against the other variants
- The older the person, the weaker the response – and that was true against all the variants
- The more obese the person was, the weaker the response – and again that was also true for all the variants
- All variants showed a weaker response 100 days after the second dose compared to 25 days
What about vaccine effectiveness after one dose
- Here the results were more worrying
- Remember that the first trials of all the vaccines, especially the Pfizer vaccine, showed a good response after one dose
- Indeed that was the behind the UK government’s decision to increase the delay between doses to 12 weeks – ‘Given the availability and resources to administer the vaccine better to cover twice the number of people with one dose’
- Now look at this figure which I have adapted from the Lancet article:
- The black diamonds show the average level of antibodies after 1 and 2 doses
- As examples I have used red arrows to point to the average values against the Indian variant
- The top purple line I have drawn shows the ideal level of response, the bottom purple line the lowest level of antibodies that can neutralise the virus: the aim should be to lie between the two lines
- After two doses, most of the samples were above the minimum in their response – but lower against the Indian and South African variants
- With the Wuhan, D416G and UK variants, one dose of vaccine does provide protection for more than half the volunteers
- That is not true for the Indian variant, with more than half the volunteers being below the minimal level of response (lower red arrow)
How bad news is all this?
- As always, need to be cautious!
- Laboratory samples of antibodies may not reflect what happens in real life in the body when we are exposed to the virus:
- Antibody levels may increase and could be high enough to neutralise any of the variants
- T cells may also be active enough
- In theory therefore two doses of Pfizer vaccine could still provide sufficient protection against the Indian variant
- This may be less likely for older and/or obese people
- Time will tell the answers to the above – but my guess is that the results of this lab-based study may turn out to be pessimistic
- One thing is clear which is that one dose – of what is the most effective vaccine (Pfizer) – does not protect against the Indian variant
- We need to ensure that younger people, now entering vaccine programmes should not relax their guard until after a second dose!
- Indeed given these results there is less defence for having a long interval between doses of the Pfizer vaccine
AstraZeneca or Moderna Vaccine?
These results refer to the data from Pfizer, but it has to be assumed that the conclusions apply to the other vaccines as well
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