Thread by @profshanecrotty

In my opinion, it is now time for J&J vaxxed to get a 2nd dose.🧵
🔵 Delta variant is so much faster
🔵 Available data (very limited) suggest weakening of J&J immunity against Delta
🔵 No news from J&J about their 2-dose vaccine

This is a personal opinion. If I had J&J this is what I would do now. I am sharing it here because I am also sharing it with friends and family. I am not an MD, so this is not medical advice, and as noted below, there is no specific clinical trial supporting J&J + RNA.

1st point:
🔵 Delta variant is so much faster

For the immune system, every day counts. T cells and B cells multiply fast. They are among the fastest replicating human cells. They can divide every 4 to 6 hours when they are going full speed. So, you can go from 1  to 10  to 100 to 1,000 more in less than 3 days.

That timing was one reason we predicted that vaccines would probably be successful against COVID-19. And they have been! Vaccines have done their job incredibly well against the original coronavirus, and they have done their job incredibly well against many variants.

But, Delta variant being this much faster and more transmissible is almost like a new virus. Thankfully, the RNA vaccines still work really well against Delta. And two doses of the AZ vaccine is doing fine.

As a reminder, your immune system has multiple ways to protect you: antibodies, T cells, and memory B cells. Antibodies are the first line of defense. Then, if you get infected, T cells and B cells are activated to multiply for several days and then kill and block the virus.

If the virus is ~2-3 days faster (4 days), that is a much harder ask of the T cells and B cells to stop the virus fast enough to prevent symptoms (and transmission). That means it is a variant with more burden on the neutralizing antibodies to stop up front.

Still, there is a lot more time to prevent severe disease. I have said for almost a year, it looks like any decent mix of antibodies, CD4 T cells, and CD8 T cells, is probably enough to prevent hospitalization level COVID-19.

And if a vaccine elicits any decent mix of antibodies, CD4 T cells, CD8 T cells and/or memory B cells, that is probably enough to prevent hospitalization level COVID-19.

What about the 1-dose J&J vac?
It has always been less than the 2-dose RNA vaccines at preventing mild cases (66% vs 95%), but J&J is convenient (1-dose), worked well against variants in clinical trial (Beta), and worked great at stop severe COVID-19, which is most important…

Also, J&J had a 2-dose clinical trial and was expected to make that available in April. (More on that later).

1-dose J&J efficacy against Beta variant being ~equal to the original strain in clinical trial was most consistent with T cells being a key component of J&J protection, because most people didn't have neutralizing antibodies against Beta (Beta is toughest variant to neutralize).

That's not the only possible explanation, but it is a simple one. And preventing ~66% of mild cases with some antibodies + T cells makes sense to me, for a virus causing disease in 6-7 days.

Here’s the Beta antibodies reference.
biorxiv.org/content/10.110…

Where are we now?
For a virus so fast it causes disease in 4 days, it is much more likely to primarily require antibodies to prevent symptoms (and transmission). The T cells and B cells can jump in to help and probably have an effect by 6-7 days, but probably not 4 days.

(Sidebar: it is a different story if the T cells and B cells are already 'home' in the nose and mouth instead of blood)

🔵 Available data (very limited) suggest weakening of J&J immunity against Delta 👇🏼

What we really want is real world evidence regarding efficacy of J&J against Delta. But there just isn't much available, and I am not aware of much more that is going to be available. So, for me, it makes sense to make a decision now, with the pieces of available information.

For me the decision is based on:

🔵 1-dose AZ not great against Delta hospitalizations
🔵 1-dose AZ only stops ~30% of Delta cases
🔵 J&J antibodies v Delta look similar to AZ
🔵 Barnstable outbreak had 3 J&J COVID hospitalizations, of 5
🔵 No news on 2-dose J&J clinical trial
🔵 Delta is faster+more deadly

🔵 1-dose AZ not great against Delta hospitalizations
AZ (AstraZeneca) is a similar vaccine to J&J, and 1-dose AZ is only 71% effective against Delta hospitalizations. 2-dose is still strong (92%, similar to 2-dose RNA). So, substantial drop with 1-dose.

khub.net/web/phe-nation…

🔵 1-dose AZ only stops ~30% of Delta cases

nejm.org/doi/10.1056/NE…

🔵 J&J antibodies against Delta look similar to AZ.

Delta has some antibody evasion, and it is probably the same for J&J and AZ.

🔵 Barnstable outbreak had 3 J&J COVID-19 hospitalizations, of 5 total.
This is some of the only "real world" data on J&J protection against Delta. It is extremely limited, but it tips the scales for me, given the speed and severity of the Delta wave.

In the Barnstable outbreak, there were 5 hospitalizations. 3 J&J, 1 Pfizer, and 1 unvaccinated. At a state population level, only 7% were J&J vaxxed. Caveats? yes. But…

…given the absence of other 'real world' data, I am stuck taking it at face value that there could be a substantial reduction in efficacy against severe COVID for 1-dose J&J.

Some of those caveats: it was a huge party week with lots of close contact and revelry, it was one outbreak, and we don't know what % of people present actually had J&J, random chance. Etc.

That ref:

cdc.gov/mmwr/volumes/7…

🔵 No news on 2-dose J&J clinical trial
Finally, The expectation when the 1-dose J&J vaccine became available was that a 2-dose J&J vaccine would be available very soon thereafter, because there was a big 2-dose vaccine trial ongoing. However, it has been many months now…

and there has been no news about trial results, or future availability of a 2-dose J&J vaccine. That has been really disappointing. Particularly since 2-dose J&J looked so good in the published phase 1 clinical trial paper on 2-dose J&J antibody, CD4, and CD8 T cell responses!

So, in sum, I fully agree with hospitals that are allowing J&J vaccinated people to get immunized with a dose of RNA vaccine (Pfizer or Moderna), to boost their immunity.

abc7news.com/coronavirus-sf…

There is NOT a clinical trial that supports that action directly. But, there is very nice data, from multiple studies, showing that AZ vaccine plus an RNA vaccine boost (Moderna or Pfizer), generates a great immune response, better than 2-dose AZ, AND better than 2 RNA doses.

For example:

nature.com/articles/s4159…

Given that J&J and AZ are both adeno vector based vaccines, it is quite likely the same kind of thing happens for J&J + RNA vaccine. [END]

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News today:

https://twitter.com/profshanecrotty/status/1423684774456008705?s=20