We now have a large amount of data preprint on Pfizer’s (NYSE: PFE) / BioNTech (NASDAQ: BNTX) first effort coronavirus vaccine candidate. This is actually the first real set of data on any of the gene vaccines, as Moderna’s (NASDAQ: MRNA) document on its Phase I trial has yet to appear (all we had was a short press release) , and a brief press release is all we also got from the Inovio DNA Vaccine (NASDAQ: INO) work.
I am very happy to see this: some of the other vaccine programs (Oxford / AstraZeneca (NYSE: AZN) and CanSino (OTCPK: CASBF), for example) have also been very forthcoming with the information, and it is extremely important that all Human testing data will be made public. I realize that doing so opens the door for many people who don’t fully understand human trial data to roam around misunderstanding things, no doubt, but the dangers of that far outweigh the need to disclose . There are also many qualified eyes, and for the public to have confidence in the vaccines that are approved, we have to have everything on the table without suspicion. No one gets a pass: everyone posts everything if they want to be taken seriously.
So what do we have today? It looks like good news. Remember that this effort actually has four different mRNA vaccine programs: two with modified RNA bases, one with additional uridine bases, and one in the “self-amplification” category. This preprint covers initial data on BNT162b1, which is one of the modified base candidates (incorporating 1-methyl pseudouridine, which should reduce the innate immune response that attacks the mRNA vaccine and also increase protein production once it enters. to cell Y encodes a trimer of the coronavirus Spike protein receptor binding domain (RBD), the most common antigen being studied in all vaccine programs worldwide. The trimerized variant uses a protein scaffold “foldon” showing three of the RBDs simultaneously on a three-dimensional matrix: it is a motif borrowed from a bacteriophage that has been used before in vaccine production.
In this study, 12 patients received 10 microgram doses on day 1 and on day 21, 12 patients received two 30 microgram doses in the same way, and 12 received a single 100 microgram dose at baseline. There were nine patients with placebo injection as a control and a panel of convalescent serum as a comparison group for the antibody response. Men / women of almost 50/50 years, from 19 to 54 years, with an average of 35 years. There were no serious adverse reactions: one patient in the 100 microgram group reported severe pain at the injection site, and several others reported moderate pain or pain after the first injection (by comparison, 2 of the 9 placebo patients reported the same ). Almost everyone reported it after the second, which is to be expected. There were reports of headache, fatigue, and fever, which were dose dependent and also more severe after the second dose, and in fact these are the ones that limited the 100 microgram group to a single initial injection. This is also exactly what you expect from a vigorous immune response.
And that seems to be what the team did. Patients were profiled on day 7, day 21, day 28, and day 35 (with dosing, as mentioned, on day 1 and day 21). RBD-binding antibodies (IgG) were detected on day 21 after the first dose, and were much stronger 7 days after the second dose (day 28). Regarding the simply geometric mean antibody concentration, the levels achieved after the first dose were 1.8x and 2.8x (in the 10 µg and 30 µg patients, respectively) the levels observed in the convalescent serum panel. After the second dose, these increased convalescence levels up to 8x to 50x (!) The antibody response was further outlined for actual neutralizing antibody titers: on day 28 (seven days after the second dose) the neutralizing antibodies 1.8x and 2.8x (in 10 µg and 30 µg patients, respectively) were observed in convalescent patients.
That definitely sounds good, as convalescent patients, remember, had already beaten coronavirus infection at the levels they’re showing. One variable in this, which we will have to address, are reports that antibody levels in such recovered patients may decrease faster than expected. You may want to try to standardize when you draw plasma from that comparison group (compared to when they stop showing viral RNA, perhaps). As Matthew Herper noted, antibody titers in convalescent patients show a much broader spread than patients treated in this study. Everyone will, of course, monitor the persistence of vaccine-induced antibodies as these trials continue as well, and we’ll get more data on the subject. Another thing I hope we will see a lot of data gathering in the trials is the T cell response: This recent preprint suggests that this might be an even more sensitive indicator than antibody titer, and that there are indeed people who develop such response without ever seroconversion (antibody development).
The FDA has published guidelines for such clinical trials, and they seem reasonable. The gold standard, of course, will be protection against coronavirus infection versus a placebo control, and just behind that is the severity of the disease in people who become infected. Blood chemistry / immunology is not addressed in detail because we still do not have enough predictive details about antibody and T cell responses (as this latest Pfizer / BioNTech manuscript also points out), but the guide leaves open the possibility of approval on such markers if we get a clear enough image later on. Any of these substitute endpoints will have to be directly related to those clinical endpoints, of course.
But back to these latter results: I agree with the conclusion of the document, which says that its findings “are encouraging and strongly support accelerated clinical development and manufacturing at risk.” So far so good, and remember, these people have three more mRNA vaccines coming in simultaneously. I’m looking forward to Moderna’s paper on its Phase I mRNA results to compare: it’s been six weeks since the press release, guys, an eternity in time COVID-19. Bring the data, everyone!
Divulge: None
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