This is really incorrect. For starters determining the optimal dose was done for the vaccine candidates in Phase 1/2 e.g.:…………
Note btw that Pfizer and Moderna attempted 3 different doses in clinical trials, and Pfizer/BioNTech had multiple candidates.

Normally you would determine the optimal dose in humans around phase 2 with data you have from phase 1 and preclinically:…
Regarding the interval, we know that for a primary series of vaccines administering doses fewer than 3 weeks apart may cause the immune response to the first dose to interfere with the second and dampen antibody responses.…
Hence, none of the vaccine doses are given fewer than 3 weeks apart. Now, in that same chapter from Plotkin's Vaccines, it notes that longer intervals between doses in a primary series produce superior antibody responses.
So that means, in theory, you could give the second doses later- but when you have a raging pandemic is that the best strategy? That means that more people are spending more time with really inadequate protection. More opportunity for variants to emerge.
Secondly, when it comes to vectored vaccines like JJJ, there are a few considerations. Adenovirus vectors are capable of a fairly unique immunological phenomenon known as memory inflation wherein T cell responses persistently expand without exhaustion:…
You also have to choose a serotype of adenovirus which most of the population has not encountered or else anti-vector immunity will prevent adequate responses. This also creates a problem for the dosing schedule.
Homologous boosting strategies with vectored vaccines will also generate a recall response against the vector that may suppress its ability to generate the antigen of interest in vivo, the spike protein in this case (though JJJ has shared encouraging data on this front).
By being a single-dose vaccine that has much easier storage conditions than the mRNA vaccines, JJJ fills an important niche for those for whom access to vaccines might be an issue. You could argue that this also has advantages from the perspective of market competition too.
That said, in light of recent findings, I have been pretty vocal that I think JJJ recipients should be permitted to receive a booster (preferably mRNA) and ideally under the monitoring of a clinical trial as there is a dearth of data here.
The assertion that human challenge studies would have gotten us here faster seems kind of facile to me and is unprovable. For one thing, given the risk of PASC, even with healthy volunteers, I have trouble with human challenge trials for COVID-19 ethically.
For another, the subject population you would have to include for them to have any chance of IRB approval would have issues of translatability of any findings that study could generate to the high-risk populations we were most concerned with e.g. elderly.…
Furthermore, human challenge studies by their nature tend to have a small number of participants which means that using them as a basis for approval does not offer any reasonable chance to detect rare AEs pre-licensure if done in lieu of Phase 3. E.g.:…
I'd suggest that we be a bit more diligent about ensuring the accuracy of the things we tweet because the claims levied here are really not fair and in some cases just blatantly untrue.

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More from @ENirenberg

2 Sep
I get people don't like masks, and I get that people may have concerns about the implications of masking children for prolonged periods. It can be really hard to weigh the known and potential benefits against the known, unknown, and potential harms of mask policy.
These sort of questions and calculations are why we have expert bodies like the AAP to guide us.

Who is more knowledgeable and more invested in the wellbeing of children than pediatricians?

Literally no one. That's the answer.…
We've known masks work. It's really disingenuous to suggest they don't. They have been used as source control long before COVID-19, and we now have a large cluster RCT of masking policy showing the effectiveness of masking against COVID-19:…
Read 9 tweets
29 Aug
I've been thinking a little bit about the concept of vaccine passports and whether we should recognize recovery from prior infection as being comparable or equivalent. Recovery from COVID-19 should not be recognized. Here is why:
To start with, it's clear that most people who recover from COVID-19 will have significant protection from SARS-CoV-2 reinfection spanning many variants. But there are caveats that are relevant here from a scientific perspective.
Firstly, I've seen many people share this preprint (…) but almost no one has done it with a critical eye or taken into account the full evidence base of literature.
Read 25 tweets
23 Aug
So now that Pfizer's COVID-19 vaccine (Bnt162b2 aka Comirnaty) has been granted full approval (BLA) by the FDA, I have seen comparisons of this decision to thalidomide.

There is possibly no example worse than thalidomide to use as an argument against the FDA's competence.🧵
In the 1950s, Chemie‐Grunenthal released thalidomide as a non-addictive, non-barbiturate sedative, wherein it was discovered to have potent antiemetic (anti-nausea) properties. That led to the petition to allow for its use as a treatment for morning sickness.
Ciba initially made the drug hoping that it would work as an anticonvulsant- it didn't. But the drug worked as a sleep aid without any apparent maximal dose or side effects. It became a drug that was used to treat virtually any condition- colds, coughs, asthma, nervousness.
Read 13 tweets
22 Aug
This distinction is HUGELY important and not at all trivial. We basically never evaluate the effectiveness of vaccines by their ability to prevent infection because it is almost never a meaningful criterion in isolation.
It would of course be awesome if vaccines could completely prevent infection. If you stop infection, every downstream consequence (illness, transmission) is abrogated. But history shows sterilizing immunity isn't a requirement for public health:
These vaccines are still holding up excellently even against the Delta variant. Even if the chance of infection may increase over time/with certain variants, the chance of severe disease remains stable, and they still do great against symptomatic disease.
Read 5 tweets
17 Aug
It really is a no-brainer that third doses will enhance people's protection after their immunity has waned some. That shouldn't be the question we fixate on. The question should be whether offering every American boosters is the best use of our resources.
Within the US itself 50.8% of the population is fully vaccinated. We have a lot of room for improvement here (this isn't even HIT for the ancestral SARS-CoV-2 variants). Offering a booster dose offers marginal gains in the way of transmission reduction.
Transmission is antecedent to hospitalizations and deaths, which are thankfully being kept in check in some (but not all) parts of the country probably thanks to vaccine uptake. So that makes sense as a target.
Read 9 tweets
4 Aug
I am very, very tired and I can't keep having this conversation so I'm just warning you now that once I post this thread I'm muting it because self-care.

COVID in kids is a big deal and it is a serious public health problem.
Usually, when you start with that as a thesis statement people will deride you based on the relative privation that adults get more seriously ill. Or that the most common outcome of COVID in kids is uncomplicated recovery.

Both are true. Neither is relevant to the question.
Firstly, previously healthy kids can and do die of COVID-19:…

Though frankly, the hyperfixation on whether or not healthy kids die of COVID belies significant ableism. You may be shocked to hear this but in fact, even kids with comorbidities shouldn't die.
Read 26 tweets

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