Thread by @michaelmina_lab

THREAD

There is (rightly) concern about the variant SARS-CoV-2 strains. I want to talk about what this means for vaccines, our future, and why we MUST have contingency plans.

This thread is in response to many questions I've received.

1/24

First, Note: I'm not doing a deep dive on specific mutations. For that, see @angie_rasmussen @jbloom_lab @K_G_Andersen @BillHanage. I am an infectious disease immunologist / epidemiologist & study viruses/vaccines. So I'll speak from that perspective.

2/24

Second Note: I do not want this thread to be alarmist.

To put it upfront, the mutations thus far do not indicate a major evasion of immunity interfering w vaccines. However, the mutations should be a wake up call to action.

3/24

The leading vaccines are each similar.

Different vehicles, but each ultimately display a similar Spike protein of SARS-CoV-2.

The combined vaccine programs are fairly narrow in scope and each provide the immune system with a limited set of epitope targets to work with.

4/24

We are now introducing these vaccines into humans globally when millions of infections are ongoing.

High cases upon vaccine introduction raise risk a mutant might arise somewhere with correct mutations to evade vaccine immunity.

This has NOT happened, but can.

5/24

We have spent so much time, money, energy accelerating vaccines that are all very similar to each other.

Thus, if a virus evolves to evade one, it could more easily adapt to evade the others too.

For this and other reasons, we MUST have contingency plans.

6/24

Out of need for speed earlier this year, we did not build in a ton of contingency plans at the levels of the individual vaccines (i.e. most spike).

For speed this made sense, but didn't account well for futureproofing

Again, this hasn't happened, but we should prepare.

7/24

A major benefit of the mRNA vaccines is they can be reprogrammed quite speedily, allowing new vaccines that target variant strains to be developed quickly.

But, should escape occur, it could mean already vaccinated ppl would potentially need re-vaccinations.

8/24

Again, I reiterate - this hasn't happened - we do NOT see variants escaping vaccine immunity now.

But this is a novel virus and it's naive to think version 1.0 of this virus would be its best.

It is evolving. And we must hope it doesn't, but plan that it will.

9/24

So what does this mean for our future?

First, we should NOT ignore it or assume it's years away.

It could be years, months, could be now. We just don't know.

Even if risk is low, the consequences of immune escape are so immense that it must be top of mind.

10/24

Why must this be top of mind??

*IF*, and this is a huge speculative *IF*, immune escape occurs and SARS-CoV-2 is able to reinfect people - it is not just more infections.

It is global markets and global economic stability on the line.

11/24

In other words, it should be one of the most important considerations at the moment.

We chose 4 closely related spike vaccines.

Immune escape has always been a possibility - while usually considered a remote possibility, this is a virus w room to adapt.

12/24

Importantly:

Reinfections would hopefully be less severe (ie not full immune escape) bc there are multiple areas (epitopes) of the spike protein that immune memory can recognize.

But we should not bank on it. We should plan for the worst but hope for easy sailing.

13/24

So, obviously the issue is immense. We cannot ignore it.

We must have contingency plans.

First: We should be thinking about diversifying our vaccines.

Live attenuated vaccines, multiple protein/peptide vaccines, killed virus vaccines.

Many ARE underway.

14/24

Second:

Given that the new variants have not yet escaped immunity but appear more transmissible, we might consider how we can speed up the vaccines we do have now, as we have discussed.

We should start single-dose trials today.

https://twitter.com/nytopinion/status/1340814910708736000?s=20

15/24

Third:

We must scale up frequent accessible rapid testing for at-home/office/school.

These will help slow spread and will not be hindered by mutations that drive immune escape.

Plus, we can adapt new tests if/as needed and move forward.

16/24

If distributed to every home, rapid tests can have a profound effect on virus spread, slowing transmission and dropping R << 1 in weeks.

They can be made in huge numbers.

We must build capacity to make these tests today.

17/24

Over 50 leading scientists and physicians in the #COVID19 response have signed a letter to congress asking for these tests to be prioritized and the funds allocated.

So far Congress has not fully committed to this specifically, Unfortunately.

rapidtests.org/expert-letter

18/24

Here, I describe the plan in @TIME

https://twitter.com/michaelmina_lab/status/1328873625894719489?s=20

19/24

And here we show some of the science and theory that underlies the use of frequent rapid testing.

advances.sciencemag.org/content/early/…
20/24

Here we discuss why rapid tests work so well as a contingency plan to vaccines even if they are not as sensitive as PCR.

Note: They are nearly as sensitive and are more specific for detecting contagious virus than PCR. They are more effective.

nejm.org/doi/full/10.10…

21/24

To conclude,

This thread is not intended to scare or fearmonger.

It is intended to answer questions many people have been asking.

IMO, immune escape should rightly be of utmost concern given the extraordinary global consequences should escape occur at this point.

22/24

We should do everything we can to reduce spread as the vaccines are being introduced.

Wear masks, distance when possible, and get rapid tests out for people to know their status, and be empowered to participate in not transmitting virus.

23/24

Everything we do to support the vaccines today, both in efficacy, speed to achieve herd immunity, speed to distribute and reduce risk of immune escape, helps them to work better.

The best thing we can do is reduce the virus as much as possible today, to help vaccines work

24/24

Another important point - we do NOT know how durable vaccine immunity will be even w current strains/2 doses.

Good biological reason to think vaccine durability may fall from high 95% efficacy after a few months.

For this too, we must have contingency plans in place now.

Also, While we should be considering single dose vaccine trials, we should also be very prepared for the magnificent 95% measured efficacy of even 2 dose vaccines to potentially fall away quickly.

We dont know, but it should be considered strongly - here’s why👇

https://twitter.com/michaelmina_lab/status/1328352029190877185