Nimrod103 wrote:Seeing as most vaccines are targetting the same spike proteins, as present on the intial virus, one must surely assume they have similar effectiveness against the original virus, and similar reduced effectiveness against the Brazil/RSA variants?
I have seen many comments (and a very little evidence) about the OxAZ vaccine having a lowered effect against the Brazil/RSA variants, but I cannot recall seeing any comments or data regarding the effectiveness of Pfizer or Moderna.
Actually they are not the same spike proteins. I wondered that myself, i.e. if you took the spike protein as sequenced very early in the pandemic (even before it was officially declared a pandemic I think) would that be exactly the coding for the spike protein that you saw in all of these vaccines. The answer is no, not exactly the same.
This article -
https://cen.acs.org/pharmaceuticals/vac ... -19/98/i38 - goes into some depth about how Moderna modified the spike protein that its vaccine codes for by inserting a couple of extra amino acids into the sequence at a key joint in the spike protein in order to keep it stabilised in the prefusion state, something thought to enhance vaccine efficacy. That article also explicitly mentions that J&J, Novavax and Pfizer have also made modifications to the original spike protein in order to try to keep it stabilised in its prefusion state. I can't remember where I read it but somewhere I saw (or maybe heard) that the AZ vaccine does not have modifications to try and lock the spike into the prefusion state and even if it does perhaps all the different vaccine manufacturers that attempt to stabilise the spike protein configuration all use different approaches where some might be more effective than others and/or the changes they have made might have differing effects on the nature of the antibody responses generated (i.e. exactly what the antibodies "see" when recognising the modified spikes. Also, the "real" spike protein is attached to the surface of the SARS-CoV-2 virus whereas the spikes generated by the mRNA and viral vector vaccines need to attach to the surface of human cells (mostly muscle cells). Does that require a change to the structure of the "tail" of the spike protein to account for it needing to bind to the different surface and if so might there be differences in terms of how convincing an impression of a "real" SARS-CoV-2 spike a vaccine spike is able to do? That's another question I would love to ask an immunologist.
On the second point re AZ efficacy the only evidence I have seen re reduced AZ efficacy against the SA strain is this small study that shows essentially none against mild or moderate disease and due to the young average age of the cohort yields no useful data at all on efficacy against hospitalisation or death -
https://www.nytimes.com/2021/02/07/worl ... frica.htmlI can't find any links right now but there has also been a fair amount of in-vitro work measuring the neutralising properties of AZ-generated antibodies against the SA strain vs against the original strain and the results show a multi-fold reduction in neutralising properties. In fairness reductions are also seen in Pfizer and Moderna in-vitro responses but I don't think it is at all clear yet how that translates into real-life protection in humans.
For some of the later vaccines some of the phase 3 trials had some percentage of the trial populations in Brazil and South Africa at times when these variants of concern were prevalent there. This article is a decent summary assuming it is an accurate report of the phase 3 trial results -
https://www.forbes.com/sites/williamhas ... 0falls,1.1. I think searching specifically for the phase 3 trial results for those various trials will get you to the original reports that break out the phase 3 trial efficacy by country which gives some idea of the ranges of reduced efficacy vs the SA and Brazilian strains.
So basically all vaccines seem to be seeing reduced efficacy against the SA strain vs the original strain at least for mild and moderate illness but, for all except AZ which was only that one small trial, still efficacy similar to or better than a typical years' flu jab.
For the UK I hope this ends up all being a bit academic. As long as none of the E484K-carrying mutations become widespread in the UK in the next 6 to 9 months there will be boosters specifically targeting those variants fairly widely administered by that time and if the school of though that the convergence of independent mutations implies that the virus has a limited number of useful and viable mutations available to it and hence might have "run out of tricks" and already "played its best card" turns out to be correct then one round of booster jabs in the last quarter of 2021 really might to all intents and purposes slay this particular demon at least as far as the UK is concerned although much will be left to be done elsewhere in the world. Yes, we will then still be left with some nasty negative fallout in terms of NHS backlogs, interruptions to children's education and higher levels of debt but we will be left with some positives too, not least the accelerated progress in various areas of medicine that I hope will carry forward for many years to come and hopefully also numerous optimisations in the NHS and various critical supply chains and manufacturing processes that will also carry forward to give ongoing benefits. And the pubs will be open again!
- Julian
