Also, it's extremely hard to compare the mRNA vaccines which have a two dose schedule with the adenovirus vaccines which mostly have a one dose schedule.
J&J has one dose. AstraZeneca has two doses. So AZ would be comparable.
Has anyone done a head to head comparison with an adenovirus vaccine and mRNA at a population level? I feel like some country must have done it, but I've stopped paying close attention to those papers.
On a population level, many months ago, when AZ wasn't approved yet, in the VAERS. mRNA had 10 million doses and the J&J vaccine 1 million at the time. I think there were 30k entries for mRNA from Moderna and Biontech. There were barely any for J&J, indistinguishable from natural coincidence I would say.
Regardless, I think that prospective studies are more accurate than retrospective population-based studies and the ones I referenced in my previous comment
are prospectively designed.
There's also been some small amount of evidence that longer delays between doses might boost efficacy even further.
I've also read reports that the likelihood of side effects (not adverse effects necessarily) increases the longer you wait for the second dose. I think I remember a talk of an immunologist who explained this as a natural phenomenon because the initial dose sensitizes potentially for a longer period of time and still builds up when the second dose is applied so that the second dose really triggers an immediate immunological reaction to the sensitized immune system, and this just for the purpose of higher antibody count.
This is also the reason why vaccines enhance the disease in case the virus mutates in any way that the built antibodies don't work anymore. Fortunately, this hasn't happened yet. But in case it happens, which is a ticking time bomb with the virus still spreading in the presence of partially vaccinated populations, there could be another outbreak that hits vaccinated people harder just like it hits people harder who have their second or third infection.
Maybe the issue is that they just didn't wait long enough after the first dose or didn't adjust them to weight and gender, so that it were mostly heavy men who decreased the overall efficacy of the first dose. Or they could have given smaller second doses but didn't wait long enough after the second dose for their outcome measurement.
But mechanistically, I also see why mRNAs liposomes just aren't the best transporters. They are immediately absorbed systemically and fuse with all kinds of cells in the whole body. Even in regions where you don't need and want any immunological response such as the epithelium or the ovaries. Wouldn't it be preferable to use a transporter that remains in the muscle tissue and can only enter muscle cells? As far as I know, such nanoparticle transporters also exist, but they are more expensive, complex, and probably patented already for cancer applications. Alternatively, microfluid buffering for a sustained release could also avoid an over-rapid response. It would have to be a subcutaneous injection then and not an intramuscular injection, which is more difficult to do.