Does the fact that Covid-19 is an RNA virus make it easier to target with an mRNA-vaccine? Could this technology also be used to target a DNA virus as well?
the limitation is an understanding of the virus+host interaction at the level of molecular structure and function.
when you have the amino acid sequence of a protien that triggers the immune system you can work backward and derive an mRNA that would be responsible for coding the protien.
there are multiple layers of complexity in getting from stage 1 to end product but this is a quick simple layout.
DNA virus has some extra tricks compared to RNA virus but the core concept is the same for both.
"Immune compromise" is generally used as a blanket term, but in many people there are specific immune deficiencies, which may or may not factor into the pathway being targeted here. For instance, natalizumab screws with immune cells' translocation across membranes, and shouldn't play a role in responding to a vaccine (I mean, if it wasn't off the market anyway).
If it's a general immune dysfunction (cancer, diabetes), they will see some benefit, but it will be much reduced - specifically because both responding to the vaccine, and responding to the virus post-vaccination, require the activity of the immune system. What this means precisely will vary with the degree and nature of the immune dysfunction: some folks might see some antibody response, and benefit from repeat dosing. Others might fail to seroconvert altogether, in which case it is what it is.
Are they using mRNA because it's easier to manufacture? Or is the protein too instable?
the liposomal capsule holding the mRNA has been engineered to deliver the mRNA to the cell and fuse with it delivering the mRNA
confoundingly the mRNA is fragile thus the ultracold dryice freezer required for holding.
the protien is stable on its own, but will be destroyed by exocytic proteases unless shielded by insertion into a membrane
I was thinking that maybe because Covid is an RNA virus, there would be a shortcut to getting the mRNA sequence for creating the spike protein. The scientists could peek at the RNA in the actual virus, recognize the spike protein, and put that in the vaccine. Whereas with a DNA virus, it would require extra work.
But from your answer, it sounds like that's not what they do? Or, maybe they could do that but it's not any easier than working backwards from the amino acid sequence.
This stuff is all very interesting!
a DNA virus must be understood somewhat to find the reading frame for the protien you need, this is the case for RNA virus as well however RNA virus are limited in size due to the instability of RNA, this means less kruft to wade through until you find the FOO
This approach is like sneaking in blueprints to a factory (cell) that makes (proteins using mRNA) whatever it has blueprints for, and gets inspectors that come around occasionally (immune surveillance), or very frequently under active infection, looking for contraband.
When the body start producing this foreign proteins in the presence of something to trigger the immune system (called an adjuvant which all vaccines use to make the body recognise as bad and not harmless/irrelevant) the immune system starts producing a response against that.
> adjuvent [sic] is not neccesary[sic] for immune response,
Completely false. Unless the immune system has been exposed to something similar before (e.g. SARS/MERS n.b. made up example I have no idea if the spikes of SARS or MERS are molecularly similar enough), no adjuvant means situation normal for the immune system. If there is nothing to signal to the immune system that this new antigen is bad then it will treat it as neutral suppressing any vaccine response, which is worse that if the vaccine had not been delivered at all.
>is nessecary[sic] for spreading out the antigen producing character among more doses
the point of booster shots is to ensure that antibodies are maintained at sufficient levels to fight off a real infection. If a response has been established, i guess adjuvants are not as necessary? (did biomed, but not a vaccine researcher) I have no idea if they are included or not for boosters.
> rather than using a concentration of mRNA that in itself produces enough protien[sic] to induce immune response
A high concentration won't do shit if the immune system doesn't have anything to activate it, it will just see a high concentration of irrelevant new, i.e. foreign protein.
This is Completely false.
Natural immunity does not require adjuvent.
spreading out a scarce valuable resource by use of adjuvent is a standard practice.
ANY complex not recognized by the MHC will elicit an invader response, the immediate vigor of this response is attenuated by inclusion of adjuvent in the final formulation of the vaccine. we would all die 100% of the time if adjuvent was required to mount immune response, to infection.
the substances you are mentioning are features of live pathogens and are being mimicked by adjuvents.
It is true that if you have a strong adjuvant, you could get away with smaller doses of the antigen, which is good for pandemic vaccines.
Source: Charles Janeway, "Approaching the asymptote? Evolution and revolution in immunology," http://symposium.cshlp.org/content/54/1.long
P.S. I wrote a COVID adjuvant grant this past spring, and my mother studies immunological tolerance. So if you disagree can you at least share some sources?
you are wrong, and its right in front of you.
please tell me about KNO3
please tell me about priming and boosting.
please tell me about innate humoral response, and cell mediated response.
i see you are still a student.
once again vaccines are not obligated to adjuvents
adjuvents increase the response to a signal allowing a weaker signal to evoke a response of threshold level.
the economic and practical bounds incurred by the expense of the immunogenic product are offset by thus exploiting, the biological property of amplification we can spread out the materials to make many more doses of vaccine requireing fewer "boost" dosages.
the big angle to work is the lack of cytoplasmic Vir-mRNA of immunogenic character. the current S protien production system is a get it shipping now product, with more work we can produce a sequence that stimulates cytoplasmic processes also involved in the induction of primary immune response.
the current sequence doesnt do that.
have a look here and see where this is heading :
https://pubmed.ncbi.nlm.nih.gov/27252702/
Interferon production at scale is tedious to say the least, it is superior to induce in vivo interferon dynamics, along with immunogenic antigen translation.
> we would all die 100% of the time if adjuvent was required to mount immune response, to infection.
Indeed, but it is required for a vaccine to function properly.
without adjuvent many vaccines would need much greater concentration of the antigen producing component.
by inducing an attenuated response, using an adjuvent, you can manufacture many more doses of the vaccine using less mRNA in each dose.
Whereas the virus encodes the whole spike, the capsid protein and whatever else the virus needs to replicate like promoter sequences and an origin of replication. It is much larger and is replicate.
Basically it skips all the viral machinery and just codes for a small piece that identifies the virus to the immune system.
It's one thing to use a viral vector to reprogram some number of cells. Due to the Emergency Use Authorization, much of the safety testing has been skipped.
Seems safe enough. Hopefully not famous last words...
And much of the safety testing hasn’t been skipped. The vaccine went through full phase 2/3 trials. The post trial surveillance phase was shortened, but it’s still ongoing.
you can see timelines here: https://www.bbc.com/news/health-55056016
tldr: nothing skipped; however it was compressed.