Thread by @sailorrooscout

This is what we have been waiting for! A study out of NIH shows heterologous COVID-19 booster vaccinations of Moderna, Pfizer, and Johnson & Johnson induce strong humoral immune responses (up to a 76X increase in nAbs) with acceptable reactogenicity profiles. Let’s discuss. 🧵

This particular study involved 458 participants. They were divided into nine groups with roughly around 50 participants in each group. Those who initially got Moderna’s vaccine got either another dose of Moderna, a dose of Pfizer, or a dose of Johnson & Johnson as a booster four

to six months after their primary immunization. Those who got Pfizer’s vaccine got either another dose of Pfizer or a dose of Moderna or a J&J booster. And those who received one dose of J&J initially either got another dose of J&J or a Moderna or Pfizer booster dose.

Still with me? Okay, good. Let’s move on. Researchers then measured antibody levels in all participants two weeks and four weeks after their booster dose. Those who received Moderna’s vaccine for their original dose and Moderna again for their booster appeared to have had the

strongest immune response, followed by those who got Pfizer boosted by Moderna and then Moderna boosted by Pfizer. Important Note: the increase in immune response with the mRNA vaccines was probably too small to really make a difference in protection in most groups. Moving on.

The most significant finding perhaps from this study is that those participants who initially received J&J’s vaccine seem to have gotten the best response if they received Pfizer or Moderna as their booster. This doesn’t come off as super surprising when we consider the robust

immune responses we have seen from mixing studies with AstraZeneca/mRNA. So, to break down the results in an easy to read format:

Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants but these were well-tolerated and the heterologous boosters were found to be safe. WIN-WIN. 💯

There are a couple caveats to this study I feel it is important to mention. Firstly, researchers tested full doses of all the vaccines- not the half-dose that Moderna is seeking authorization for in its booster. What is important to know is that even a half-dose of Moderna’s

vaccine has been shown to be extremely effective, so far as to increase antibodies against the Delta variant by 42-fold. That’s JUST the half-dose. Secondly, researchers measured antibody levels two and four weeks after the booster. So there's a chance antibody levels from a

J&J booster could continue to rise with more time as we have clearly seen in other studies (see my previous threads or just ask me to repost them). Researchers here are assuming that higher antibody levels translate into more protection.

While this is potentially true, we KNOW other factors play a role, such as responses by other parts of the immune system. Hello? Cell-mediated immunity! Don’t forget those T-cells- they eventually get on their way and help IMMENSELY! So, what you need to know from this here study

data is that homologous and heterologous booster vaccinations were well-tolerated and highly immunogenic in adults who completed a primary COVID-19 vaccine regimen at least 12 weeks earlier. This data will be reviewed by advisers to the FDA between today and tomorrow as part of a

meeting to consider requests from both Moderna and J&J to authorize booster doses of their vaccines. You can find this study here: medrxiv.org/content/10.110… AND now VRBPAC’s presentation slides on heterologous boosters here: fda.gov/media/153128/d…