Potential danger of repeated mRNA boosters

[BT63]

Having had 5 jabs to date, all mRNA, I am seriously thinking of having no more, unless something else changes anyway. The risk of Covid appears to be well down the list of current health risks if media coverage (or rather the lack of it) is anything to go by. And I rarely see anyone wearing a face covering these days.

40 months on, can we finally declare this done and dusted now?

Covid went through our household a couple of months ago and everyone was hit pretty hard by it, as bad as flu, with classic original symptoms of high fevers, sweats, chills, nasty cough, loss of smell/taste for 2-3 weeks etc. None of us had been vaccinated for probably >1yr.

If I was 65+ or had significant health conditions I would try to have an annual vaccination for Covid, as with the flu vaccine. In those groups of people, I think the risk of death from Covid is much greater than the risk of complications from the vaccine.

When Covid was still very disruptive and boosters and subsequent boosters were being talked about as being compulsory every three months, I was concerned that there might be side effects from such frequent vaccination.

[Julian]

Rubbish, the virus spike protein is relatively strongly conserved so there will be major similarities between spike proteins. The trial with the Sanofi vaccine showed it gave good protection against Omicron variant so it won't be a placebo. There is also evidence that heterologous vaccination (ie being given a variety of different vaccines to covid) produces an improved response to the virus.

If you are really interested in how mutations in the spike protein affect response to vaccines have a read of:
https://www.nature.com/articles/s41579- ... 73-0#Sec11

a 2021 Nature Microbiology Reviews review article.

or this one:
https://www.nature.com/articles/s41579-022-00841-7

from January this year.

In your second link it says this:

With more than 15 spike receptor-binding domain (RBD) mutations and a number of antigenic deletions and substitutions in the amino-terminal domain (NTD)43,44, BA.1, BA.2, BA.4 and BA.5 are very poorly neutralized with first-generation vaccines and by pre-Omicron infection-derived antibodies

So a vaccine based on the Beta spike protein is going to be a first-generation vaccine as that generates pre-Omicron antibodies. And this is against virus mutations that are well over 12 months old now, so the current virus will have mutated further.

You can also reference the regular reports/account of "breakthrough" infections, as well as the ever decreasing period of vaccine efficacy(what are we down to 6 weeks now?), which all point to an ineffective vaccine.

I will believe previous infection is the heavy lifting now and the vaccine is mainly a placebo, while you can believe the vaccine works. As long as it means we don't return to the disinformation and nonsense of 2020/21.

It's about more than just antibodies though, there are also T-cell responses to consider and there the range of spike-derived epitopes (since we're only considering spike protein based vaccines) are really quite well conserved across variants and there are more to choose from vs potential neutralising binding sites for antibodies against spike. There's also other neat stuff to do with T-cell epitope presentation that makes it harder for viral mutations to evade recognition in a population as a whole because different people will present different subsets of all the potential epitopes (that same mechanism is one of the things that makes donor matching for organ transplants more difficult).

Here's one article and associated paper discussing this in more detail - https://www.news-medical.net/news/20221 ... iants.aspx

I don't claim to be an expert and haven't been keeping as up to date as I used to but my impression is that yes, the significant rise in SARS-CoV-2 antibody levels that a booster generates is indeed now pretty widely accepted to be fairly short-lived, variable across the population since people react differently and I have read in the past about noticeable waning of antibody levels after 3 months but I wouldn't be surprised if for some people that 6 week figure has validity so I wouldn't want to pick an argument with you there. T-cell activity however appears to be much more durable and while it won't stop an infection starting hence all these "breakthrough"(*) infections, those T-cell responses are of great value in supressing the viral replication rate and ultimately clearing it from someone's system more quickly thus reducing the likelihood of an infection becoming severe.

- Julian

(*) I think a lot of virologists and immunologists don't like that "breakthrough infection" terminology since it can be taken to imply that something wrong or unexpected has happened whereas the consensus (virtually unanimous I think) understanding now is that the currently available SARS-CoV-2 vaccines can't be expected to block all chance of infection but instead should be considered as a way of reducing the chance of any infection becoming severe. I think in retrospect a lot of experts regret the way expectations were set during the early days of the vaccine development and roll-out, and the rate and extent of SARS-CoV-2 mutation made matters worse re vaccine antibody escape, but we are where we are and it is still important to now understand that realistically we can't expect current vaccines to confer anything like sterilising immunity but that they still have value as a later line of defence against a bad outcome from an infection.

[scotia]

The Spring 2023 Covid Booster program in England will use vaccines from Pfizer/Biontech, Moderna, and Sanifo.
Here is my layman's understanding as to what they may contain. Corrections are welcome.

The genetic sequence of the Covid strain circulating in Wuhan during December 2019 was published by China in January 2020. This was the strain used by Pfizer/Biontech and Moderna in the development of their “original”, first generation, Covid vaccines, which were introduced in 2021. They proved effective against later Covid versions which circulated in the UK (e.g. Alpha , Beta, Delta), but had limited success with the Omicron variant. Both Pfizer/Biontech and Moderna introduced bivalent vaccines for the Autumn 2022 boosters - and these contained the original vaccine plus a new one targeted on the Omicron BA.1 version. For Spring 2023 boosters they have both introduced an updated bivalent vaccine which contains the original vaccine plus one targeted on Omicron BA.4-5 variants. I assume these will be used in the current booster program. The Pfizer/Biontech and Moderna vaccines are Messenger RNA vaccines.

The third vaccine to be used in the Spring 2023 booster program is produced by Sanofi. It is a protein based vaccine which is produced in a different manner to the Messenger RNA vaccines. Its name is “VidPrevtyn Beta” which indicates that it is developed from the Covid Beta variant. This is a later variant than is used in the first generation “original” Pfizer/Biontech and Moderna vaccines, but it is earlier than the Omicron variants that are included in the Bivalent Pfizer/Biontech and Moderna vaccines. However It also contains GSK’s adjuvant that is claimed to boost your immune response. In comparison with the use of an “original” Covid vaccine as a booster, it triggered a higher production of Omicron BA.1 antibodies.

From the Lancet:-https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00042-X/fulltext

Could Beta variant containing COVID-19 booster vaccines tackle Omicron variants?

Disappointingly it came to a conclusion

The relative performance of a Beta-booster vaccine compared to Omicron-containing booster vaccines will provide valuable data to inform vaccination policy decisions on variant-containing vaccines. As far as we know, a direct comparison of Beta-containing and Omicron-containing booster vaccines has not been done or published.

[scotia]

It seems to be a difficult name to spell correctly. In the above I have used the name Sanifo (wrong) and Sanofi (correct ).

[daveh]

When I was searching for info on the Sanofi vaccine I googled for trial data and got to the MHRA site on clinical trials. There are a couple of trials running to compare the Sanofi vaccine with the bivalent mRNA vaccines for efficacy against newer Omicron strains, but they are not due to complete until later this year, and there will be some delay while the data is processed before the results can be published.

[CliffEdge]

I don't think I'll have another Covid booster. I seem to remember reading somewhere a while back that they become ineffective after the fourth one but I've no idea where I read it.

I've got a feeling that what I read was something to do with something called "immune imprinting". It's all over my head TBH.

[scotia]

I don't think I'll have another Covid booster. I seem to remember reading somewhere a while back that they become ineffective after the fourth one but I've no idea where I read it.

I've got a feeling that what I read was something to do with something called "immune imprinting". It's all over my head TBH.

For up to date information, read https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142218/ , published April 2023, entitled
"Immune Imprinting and Implications for COVID-19"
Immune imprinting is a reported feature of mutating viruses - e.g. influenza and Covid. The extent to which it may seriously affect repeated vaccinations for Covid are as yet unknown. However it does not appear to have seriously affected long term repeated vaccinations for influenza.
So I think its a lot more complicated than your quote that Covid vaccinations are "ineffective after the fourth vaccination". It would be useful if you could find the reference to that quote.

[Julian]

I tucked this post in here since it's related to boosters although not any suggested dangers thereof.

This is a reasonably concise (just over 13 mins) interview with someone on the FDA Vaccine Advisory Committee. From my various explorations during the pandemic I have come across the guy being interviewed (Paul Ofitt) a fair amount and he seems to be well respected in the relevant scientific communities.

The video covers the currently ongoing discussions about the possible changes for the next booster program probably in late autumn and also some looking back at the previous decision on the last booster, i.e. the decision to make it bivalent with half of the dose being for the original Wuhan strain. It does also briefly mention immune imprinting.

The video is here - https://www.youtube.com/watch?v=Smfjyy9cgV4

As a note, Ofitt was also on the advisory committee when the FDA was debating the original bivalent booster prior to authorisation and was one of I think only 3 of that committee of about 20 members to vote against the bivalent booster (preferring as I understand it to use the original monovalent vaccines for the booster) on the basis that the evidence/data that was being presented to the FDA advisory group at that time was insufficient to demonstrate that the bivalent boosters being proposed would be significantly more effective than simply administering another dose of the existing monovalent boosters. He is claiming in this interview that data has validated his concerns but I have no idea if that is fair or not. Sadly the video description doesn't contain any links to a few studies that Paul Ofitt mentions towards the beginning re efficacy of the bivalent booster vs the original monovalent booster e.g. a French study. I still thought the interview was interesting though.

Presumably similar discussions about the composition of the next booster to be rolled out are also going on within in the UK's MHRA.

- Julian