...I’m confused about what method you’re even trying to gesture at.
They’re viruses*, they need a full set of environmentally-provided cell machinery to replicate or produce proteins: ribosomes, transcription machinery (ex: t-RNAs), ATP, the works. They need cells, so you’d need need at least a cell culture. All of biology has heavily optimized protein assembly lines, you’re not going to beat it acellularly.
The cells near the outside of an egg are probably used because they’re an elegant and self-contained little solution to sterilization (against everything but your virus) and the quality-control problems you’d have to contend with otherwise. It’s not really about the protein content, mostly.
(Cell culture is probably more expensive than eggs because 1) bioreactors are kinda expensive, 2) bioreactors are a bit of a pain to maintain, and sterilization is hard, two problems that using an egg pretty neatly solves, and 3) which cell culture will work best is surprisingly hard to predict, you basically have to test it experimentally.)
* Well, technically it’s weakened viruses, or single-gene plasmids, or something similar. The need for cells still holds either way.
…I’m confused about what method you’re even trying to gesture at.
Eggs do have a lot of ovalbumin where it’s not really desireable for that to end up in your final vaccine but I don’t think this is a discussion to have at a point where our key issue is scaling up vaccine production.
If you have to order the steralized eggs a year in advance, and we want our COVID-19 vaccine before a year is over, that suggests to me that we also have other problems.
If I understand the work Moderna is doing for their COVID-19 vaccine and read the paper where they describe their framework, it seems to me that they use human cell lines:
The modified mRNA was synthesized enzymatically and packaged into lipid nanoparticles (LNPs). Incubation of LNPs containing IgE signal-prM-E mRNA (IgEsig-prM-E) with 293T or HeLa cells resulted in efficient expression and secretion of ∼30 nm SVPs
Just like Moderna, CureVac which is another of the companies that want to produce a COVID-19 vaccine also focuses on delievering mRNA and not viruses. I didn’t immediately find information about how CureVac gets their mRNA but it wouldn’t surprise me if they also don’t use eggs.
Whoah, lipid-coated mRNA vaccines, not as an intermediate step but as the actual delivery method? That’s actually new to me! Sounds like it’s mRNAs coding for some subset of the viral proteins, which probably get assembled into proteins in your cells and then get used as something for antibodies to respond against. mRNAs should then just degrade themselves with time.
I have no idea what the most efficient method for producing those is; I am very used to vaccines being protein-based. This probably is in the realm where it’s simple enough that modifying PCR-protocols to produce RNA instead might actually work reasonably well, although RNA is generally more fragile and error-prone and that could be a problem.
You’d be using nucleotides, not amino acids, but mRNA from DNA is a short-enough assembly line that you might not need cells to do it.
(Protein production has a lot of dependencies. mRNA transcription should basically just require your DNA of interest, nucleotides (x4), and a transcriptase protein. Maybe add a transcription factor or two.)
HeLa definitely is a human cell line (although that was for Ebola, they may end up using a different cell line). That’s good, that probably scales up easily.
“Disease X could emerge suddenly and have deadly consquences—we’ve seen this happen with Ebola, MERS coronavirus, Zika, and countless other diseases. That’s why we’re striving to develop rapid-response vaccine platforms—like CureVac’s mRNA technology—to defend against these unknown pathogens. CEPI has now established partnership agreements totaling more than $50 million in three such platforms”.
It seems that the third mRNA vaccine company is BioNTech.
Johnson & Johnson appears to be using a more traditional approach in which the virus is inactivated so it can’t replicate but can still express viral proteins. The approach takes a little longer for both the development and manufacturing scale-up steps. On the plus side, Johnson & Johnson’s slow-but-steady approach could create a vaccine with a better immune response.
There’s a forth company with Inovio Pharm that also develops a COVID-19 vaccine. It’s technology is based on delievering DNA based.
I have the impression that the mRNA/DNA ways of vaccine delievery allow for faster development of a vaccine then the old fashioned protein based way.
...I’m confused about what method you’re even trying to gesture at.
They’re viruses*, they need a full set of environmentally-provided cell machinery to replicate or produce proteins: ribosomes, transcription machinery (ex: t-RNAs), ATP, the works. They need cells, so you’d need need at least a cell culture. All of biology has heavily optimized protein assembly lines, you’re not going to beat it acellularly.
The cells near the outside of an egg are probably used because they’re an elegant and self-contained little solution to sterilization (against everything but your virus) and the quality-control problems you’d have to contend with otherwise. It’s not really about the protein content, mostly.
(Cell culture is probably more expensive than eggs because 1) bioreactors are kinda expensive, 2) bioreactors are a bit of a pain to maintain, and sterilization is hard, two problems that using an egg pretty neatly solves, and 3) which cell culture will work best is surprisingly hard to predict, you basically have to test it experimentally.)
* Well, technically it’s weakened viruses, or single-gene plasmids, or something similar. The need for cells still holds either way.
Eggs do have a lot of ovalbumin where it’s not really desireable for that to end up in your final vaccine but I don’t think this is a discussion to have at a point where our key issue is scaling up vaccine production.
If you have to order the steralized eggs a year in advance, and we want our COVID-19 vaccine before a year is over, that suggests to me that we also have other problems.
If I understand the work Moderna is doing for their COVID-19 vaccine and read the paper where they describe their framework, it seems to me that they use human cell lines:
Just like Moderna, CureVac which is another of the companies that want to produce a COVID-19 vaccine also focuses on delievering mRNA and not viruses. I didn’t immediately find information about how CureVac gets their mRNA but it wouldn’t surprise me if they also don’t use eggs.
Whoah, lipid-coated mRNA vaccines, not as an intermediate step but as the actual delivery method? That’s actually new to me! Sounds like it’s mRNAs coding for some subset of the viral proteins, which probably get assembled into proteins in your cells and then get used as something for antibodies to respond against. mRNAs should then just degrade themselves with time.
I have no idea what the most efficient method for producing those is; I am very used to vaccines being protein-based. This probably is in the realm where it’s simple enough that modifying PCR-protocols to produce RNA instead might actually work reasonably well, although RNA is generally more fragile and error-prone and that could be a problem.
You’d be using nucleotides, not amino acids, but mRNA from DNA is a short-enough assembly line that you might not need cells to do it.
(Protein production has a lot of dependencies. mRNA transcription should basically just require your DNA of interest, nucleotides (x4), and a transcriptase protein. Maybe add a transcription factor or two.)
HeLa definitely is a human cell line (although that was for Ebola, they may end up using a different cell line). That’s good, that probably scales up easily.
From last year: From CEPI awards US$ 34M contract to CureVac to advance The RNA Printer™
It seems that the third mRNA vaccine company is BioNTech.
It seems that Johnson & Johnson is still developing a vaccine the traditional way:
There’s a forth company with Inovio Pharm that also develops a COVID-19 vaccine. It’s technology is based on delievering DNA based.
I have the impression that the mRNA/DNA ways of vaccine delievery allow for faster development of a vaccine then the old fashioned protein based way.