It's important to note that the AstraZeneca vaccine is adenovirus based [0], not mRNA based like the Pfizer and Moderna candidates. It was to be expected that this approach could cause more complications. mRNA vaccines have their own issues, but they do not involve live viruses being injected [1]. Instead they use lipid nanoparticles as a substrate to enter the body's cells [2].
> rather than producing them outside the body and then injecting them
That's not what the Oxford/AZ vaccine does, is it? From what I understand, it's a viral vector vaccine engineered to deliver DNA that encodes the SARS-CoV-2 spike protein into human cells and induce them to express the protein, stimulating the immune response.
The plan was never to introduce spike protein "produced outside the body." The mechanism of action is getting the body to produce spike protein and learn to attack it as foreign. If the Oxford/AZ vaccine doesn't "take advantage of your own cells to produce the spike protein," I don't know what does.
Yes, the ChAdOx is an adenovirus carrier (chimp? to minimize human pre-infection) while Moderna and BioNTech as the parent states involve injection of mRNA (not DNA although there are other vaccines that do that) lipid particles that human cells then generate spike protein to simulate viral infection.
There are still other attenuated virus and other vaccines under development, they just haven't reached Phase III. Novavax even does something similar to what you describe (spike proteins with adjuvant), but it's also not past Phase I/II.
I think COVID is going to be make or break for mRNA, at least for infectious disease. It's either going to usher in an exciting new era of treatments, or we're going to see a lot of funding dry up and shops close. I for one obviously hope for the former, but given the prior actions/statements of some in Inovio, Moderna, et al, it gives me pause.
The chimpanzee adenovirus is used as a vector, with its payload replaced with instructions to manufacture SARS-CoV-2 spike protein.
Virus enters body, hopefully survives immune system long enough to insert instructions into your cells, your cells churn out tons of copies of coronavirus spike protein, your immune system sees the surfeit of spike protein and develops a response (antibodies and T* cells).
> Imagine a 4 billion year old codebase, written by dice throws and unit testing.
That's a great analogy, except it doesn't go quite far enough. The code for the toolchain that compiles the codebase (not to mention the unit testing framework) is just as old, and written the same way.
Note to self: while the code (including the toolchain code etc.) is in a monorepo, it is actually surprisingly modular. OTOH, much of the functionality was implemented by copy-and-paste of existing code elsewhere in the repo, and the copies then diverged with subsequent modification.
His point was more along the lines of it being poorly designed.
Evolution isn't going to nicely separate functionality into clean, single-purpose biochemical pathways.
It's going to overload something that it already has to support a new feature, leading to a rat's nest of intertwined effects.
The hard part in drug development isn't affecting your target: that's pretty easy to guarantee with modern tools. It's finding out that that target also governs 10 other, completely unrelated bodily functions.
It sounds harmless because it omits the incredibly complex process of developing immunity.
Your body basically is trying to do a sort of brute force/random combination of immune cells on the retrieved virus spike proteins until it comes up with the right combination.
This process can result in B cells that produce antibodies which stick to virus proteins but also stick to your own cells. The B cells are essentially permanent, that’s how you develop lasting immunity, that unfortunately also means you have lasting immunity on one of your own cell types — autoimmunity https://en.wikipedia.org/wiki/Autoimmune_disease
A 50000 people study is likely to see adverse events completely unrelated to the vaccine. Halting the trial is not a sign that they think it is related either, since it is protocol to rule things out before continuing.
Yes, they don’t replicate virons that could be assembled the virus was modified to mainly replicate the spike proteins since your cells send samples of anything they replicate to the cell wall for your immune system to monitor and sample this is how the adaptive immune response is achieved.
Thought Emporium has a decent video where he modifies an Adenovirus to inject the lactase gene into the cells of his intestinal tract.
https://www.youtube.com/watch?v=J3FcbFqSoQY
[0] https://www.astrazeneca.com/media-centre/press-releases/2020...
[1] https://www.phgfoundation.org/briefing/rna-vaccines
[2] https://www.nature.com/articles/s41586-020-2639-4