A bit concerned by scientists claiming with absolute certainty that VOCs will not evade vaccine responses & that this has never happened in 'real people'. This has happened in clinical trials & dismissing very real risks provides false reassurance & prevents pre-emptive action.

First, I want to say that the current variant dominant in the UK at 98-99% is the Kent variant (B.1.1.7), and the vaccines being used in the UK are highly effective against preventing symptomatic and severe disease with this.

Please do take the vaccine if you are offered it.

Vaccines are a hugely important resource. And it's important to address the real risks posed to vaccine efficacy by new variants- rather than dismiss these without basis. This is the only way we can take pre-emptive action to protect vaccine resources. Which we must try to do.

Blind optimism and hope isn't what we're here for as scientists. We're here to communicate facts. And these are the facts:
Vaccine effectiveness is reduced with some variants, and for some vaccines- this is not just data from the laboratory, but from clinical trials.

Some would say 'But we still have high efficacy with severe disease'
There is no certainty about this for some vaccines. Astra which is widely used in the UK showed no efficacy against mild-moderate disease with B.1.351 as per the trial report in NEJM.

While one can hope for some efficacy against severe disease, or with alternative dosing regimens, there is absolutely no guarantee of this - and anyone guaranteeing this with certainty is not basing claims in evidence that exists in data from 'real people'.

Vaccine efficacy against symptomatic disease with B.1.351 is also reduced with Novavax and J&J (although still high). We know for Novavax at least that effectiveness against severe disease is still preserved.

What does this mean?

It's really great if effectiveness against severe disease is preserved, because it protects the individual. However, there is evidence to suggest that effectiveness in preventing *infection* with some VOCs may be lower. What does this mean at population level?

Ultimately, the aim at population level is to reach herd immunity- which is the threshold at which the R drops below 1 just as a result of vaccine related population immunity. This threshold depends on the impact of vaccines in preventing infection & transmission.

So while effectiveness in preventing severe disease is vitally important, reduction in effectiveness in preventing infection & transmission can still have important implications for the pandemic at population level.

As I've said before vaccine effectiveness is a pyramid. There is efficacy in:
1. Preventing infection
2. Preventing transmission (lower viral loads)
3. Prevent symptoms
4. Preventing moderate disease
5. Preventing severe disease.

5. can be preserved while 1, 2 & 3 may be reduced, as we've seen with vaccines with B.1.351. More robust immune responses are needed to prevent infection that to prevent severe disease - so these will be the first ones to go with escape- with impact on reaching herd immunity.

This means that either a greater proportion of the population may need to be vaccinated to reach the herd immunity threshold, or perhaps that it may not be possible to reach this through vaccines alone, if impact on transmission is not sufficiently high.

I know I'll be criticised by some suggesting that this thread causes undue alarm. I don't believe it does. As I've said it's *because* vaccines are such an important part of pandemic response, that we need to *protect* them. And to do this we need to act proactively to do this.

The best way to do this is acknowledge risks to vaccine effectiveness posed by VOCs & minimise these by preventing import/spread. Dismissing real risks - however well intentioned- can prevent us responding to these proactively based in optimism that may not bear out in reality.

Just want to add for anyone claiming that we don't have data on severe disease efficacy for Astra and B.1.351. Yes, we don't- because the trial was suspended after interim results showing no/minimal efficacy against mild-moderate disease, as it was not deemed ethical to continue.

SA stopped Astra roll out based on the trial- which means we'll probably not have these data at least in the clinical trial context - as the risks of possible lack of protection from Astra were deemed to be too high for the govt or the trial team to take, based on their data.

Link to the NEJM article is here for reference: https://www.nejm.org/doi/full/10.1056/nejmoa2102214