The UK, US, Canada and other countries have announced a programme of a 4th vaccine dose, with the possibility of using the new vaccines developed by Moderna and Pfizer, designed to increase protection against the Omicron variant. Studies published last week have evaluated whether these new vaccines offer any additional benefit
The existing vaccines
- The vaccines in use up to now were all developed to combat the original Wuhan strain
- They have been of proven success in reducing the severity of Covid-19 infection
- Somewhat surprisingly, this success has continued despite the emergence of new variants over the 18 months since these original vaccines were launched
- The problem with these vaccines has been their limited ability to prevent infections happening. Although most infections – especially with the current prevalent Omicron variants – are mild, there are still concerns about long Covid-19 in some sufferers as well as work and school absences from mild infections
- Some of the ‘Wuhan’ vaccines’ failure to prevent infection is due to waning immunity but some may be related to the reduced protection they provide against the new variants
- Thus it would appear to make sense to develop vaccines that are effective against the newer strains
Why haven’t new vaccines been developed before now?
- In fact new vaccines have been developed almost continuously since the Wuhan vaccines were released
- The two companies marketing mRNA vaccines (Pfizer and Moderna) from the outset were clear that this technology could easily be modified to create new vaccines, if new strains arose
- Indeed regulators offered a ‘light touch’ approval process – ie because the initial vaccines that resulted from the technology were effective and safe, there was a low bar for the regulators to allow newer vaccines derived from the same approach.
- The drug companies though had 5 problems until now in mass producing a new vaccine:
Pfizer and Moderna’s new ‘bivalent’ Vaccines
- On August 15th in UK and September 2nd in USA and Canada, approval was given for the use of so called ‘bivalent’ vaccines
- The term ‘bivalent’ means simply (the clue is in the ‘bi’) that the vaccine is designed to be active against both the original Wuhan strain and Omicron as well
- Actually, having vaccines that work against more than one variant is not unusual: I have discussed previously in this blog how the annual flu jab is ‘quadrivalent’, to be effective against both 2 strains of influenza A and 2 strains of influenza B
How easy is it to show that these new bivalent vaccines work better than the original vaccines?
- It’s not a given that these vaccines would be more effective
- None of the previous vaccines have been particularly effective at stopping transmission of mild illness, so why should the new vaccine be any different?
- It is of course also difficult to do studies to show that they are more successful than the original vaccines for several reasons
- The original studies involved tens of thousands of individuals who were randomly allocated to either the Wuhan vaccine or placebo and then followed up to see who got infected
- To mount such a trial comparing the new versus the original vaccines might need hundreds of thousands of participants if the difference was only modest
- Most people in the west are already protected by previous vaccines and previous infections, so whichever vaccine a participant in a trial received, then most cases of Covid-19 would be mild and would require regular and expensive PCR testing and follow up of all the study subjects
- Thus the only data we have is from laboratory studies comparing the level of immunity in the blood (ie antibodies) between study participants receiving the Wuhan and those receiving the bivalent vaccines
- Scientists have now studied these laboratory results and using computer modelling tried to predict how they would translate into clinical success
- Indeed the scientists in a paper published last week, did exactly that. They calculated the likely risk of infection: both (i) any infection with symptoms and (ii) severe infection (leading to being in hospital) in 3 groups of people:
- Those who had just had the normal course of vaccines
- Those who had a booster with the original Wuhan vaccine
- Those who had had a booster with the new combined vaccine
- What they found is shown in the graph below
- The blue bars show the success against any infection with symptoms
- The red bars show the success against serious infection (ie hospital admission)
- The top bars (no booster) show that there was only 50% protection against getting any infection with symptoms and around 90% against severe infection
- The bottom 2 sets of bars show that a booster, either with the Wuhan vaccine or with the combined new vaccine, produces almost identical protection
- Basically it’s not what booster vaccine you get, it is the fact that you get a booster that makes the difference
- I have not discussed safety, but I can’t see any reason why there should be any different safety concerns with the new combined vaccine compared to the original vaccines
- Our pre-existing level of immunity, from our previous 3 doses plus any natural immunity we have acquired from infection, still provides good protection against serious infection
- A further booster will be beneficial but probably if this was with the Wuhan vaccine it would probably have been fine
- Since the companies are now producing the bivalent vaccines for mass use, then that is what we will receive, but don’t expect that they will provide any special protection against getting minor infection from the current or any new main circulating variants
Appendix of interest to the more mathematical scientists amongst the readers!
- The above result was somewhat surprising, as I assumed the variant-based vaccines would give more immunity than older vaccines
- The reason seems to be that because of our existing immunity, it is much harder to show additional benefit
- In other words: if we had the pandemic starting now, and none of us had any pre-existing immunity and we were faced with the Omicron variant, we would be much better protected if we had the new combined vaccine
- In practice we have some protection although the exact level can only be guessed at as it wanes over time
- This is shown in the diagram below
- The percent on the y axis shows how much greater is our protection from having a booster compared to not having a booster
- The curves are not straight horizontal lines because our pre-existing immunity also provides protection
- Thus at the extreme (right on the diagram) if there was 100% immunity prior to having any booster, then there is no scope for any additional protection
- The lowest (yellow) curve shows the situation for a booster that is based on a vaccine not related to the main variant causing infection (eg the situation of giving the Wuhan vaccine today when most people are getting Omicron).
- The highest (brown) curve shows the situation for a booster that is based on a vaccine which is related to the main variant causing infection (eg the situation of giving an Omicron based vaccine today when most people are getting Omicron)
- Ignore the middle (orange) curve, which is the average
If you would like to receive email notifications of new posts on this blog just click this link and enter your email at the bottom of the home page: https://makingsenseofcovid19withs.com
3 replies on “The new booster vaccines from Moderna and Pfizer: what are the facts?”
Alan, this is really objective and helpful for many reasons so thanks for spending the time on it. As an older but very fit adult, I have been invited to have what is effectively a fifth jab in October (2 Astra Zeneca and 2 Moderna already). I had very mild Omicron once as an infection and am not vulnerable apart from age. Do you consider that repeated boosters will always be needed – it is difficult for a lay person to tell.
I have a very similar, but extended question. This was a very interesting analysis. It raises the questions, do we need boosters, and do we need them now? In previous years I was told by medical friends to have a flu jab later in the season – maybe November/December, as this would boost immunity in the peak season of illness – January/February. Would this not apply to Covid too?
We are being offered a flu jab and a Covid booster by our GP practice, but my strong inclination is to wait.
I am also on my 5th jab with 2 Novavax and 2 Moderna. I have managed to avoid any detectable Covid. So a further question – if Pfizer is the same technology as Moderna, is it essentially the same vaccine, or would this be a 3rd different vaccine?
A great question to which no-one knows the answer. The issue is one of how much does immunity wane, which varies between individuals. It is not practical or cost effective to do antibody testing prior to any booster campaign so the ‘easiest’ option is to give everyone a booster. Apart from short term mild dose effects the vaccines are very safe so in a sense “if they do no harm, then we should have them”. It is analogous to annual flu jab in some ways (although the flu vaccines do also substantially reduce mild infections as well). Wearing my public health hat my question is the cost benefit of vaccinating the entire population (or whatever age group is chosen) compared to what else the money and staff time could be spent on!