The news is …well, better. There are, at least, two functional vaccines now being given.
First Vaccine Approved in the U.S. and Europe.
Pfizer BioNtech: Two-shots, given 21 days apart.
Two big researchers at BioNtech, Katalin Karikó, and Drew Weissman, have been working on/with the artificial mRNA methods used in the vaccine for many years. One of their papers:
Katalin Karikó, Michael Buckstein, Houping Ni, Drew Weissman. 2005. Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity 23: 165-175.
The idea for the vaccine, eventually, was design and create mRNA in a petri dish. The mRNA is delivered to the cells of patients inside a package (nanoparticle). The mRNA holds the code to create a protein that is like a surface protein on the Covid-19 virus. Our immune system will recognize and then respond to the protein. One of the responses of our immune system is the production of memory cells. These cells retain the information about the invading protein and, should the person get the actual Covid-19, they pass the information quickly to other cells that produce antibodies against Covid.-19.
The second vaccine approved:
Moderna” Two-shots, given 28 days apart.
Based on the same initial mRNA work, Moderna has developed a slightly different vaccine. It uses mRNA, but a different sequence, and it is delivered in a different package (nanoparticle). The difference in the delivery package is the reason for the difference in the temperature that the vaccine must be kept at before being prepared for use. This vaccine was developed with the help of researchers like Kizzmekia Corbett and Barney Graham.
Other vaccines in the works use other technology:
AstraZeneca and Oxford vaccine: this vaccine uses another virus (basically the cold virus, cleaned out and then stuffed with other materials), to house and deliver a small piece of the genetic material from the Covid-19 virus. This vaccine may require multiple booster shots. It has also run into difficulties with safety.
Janssen, Johnson and Johnson:
Similar to the AstraZeneca vaccine, this vaccine uses recombinant adenoviruses. Again, basically a cold virus repurposed to house a small amount of the Covid-19 genetic material. As with the other recombination vaccine, this one may require multiple booster shots.
Novavax:
This vaccine is made from the protein antigen (similar to the one the mRNA vaccine makes). This is made by a recombinant protein technology. The vaccine also contains a immune system booster.
The new technology is the mRNA delivery and astounding possibilities are being touted (a universal flu vaccine, for example). But this type of work does not appear overnight, and the long history of science often goes unappreciated. So…here is a quick, slightly annotated, history of the science needed for this to occur: This is a pared down version.
Watson, J.D., and Crick F.H.C. 1953. Genetical implications of the structure of deoxyribose nucleic acid. Nature 171, 964–967.
Along with the next two papers, this was the announcement of a proposed structure of DNA and evidence based aspects that were known. This series of papers started the whole new field of molecular biology.
Franklin RE, and Gosling RG. 1953. Molecular Configuration in Sodium Thymonucleate. Nature 171: 740–741.
Wilkins MHF, Stokes AR, Wilson HR. 1953. Molecular Structure of Nucleic Acids: Molecular Structure of Deoxypentose Nucleic Acids. Nature 171: 738–740.
Rather than a massive exploding of knowledge, next came the slow boil that is often science. Paper after paper emerged with people working on DNA and RNA and trying to determine just how this series of genetic molecules actually functioned. Here are a few of the most prominent papers.
Gamow, G. 1954. Possible relation between deoxyribonucleic acid and protein structure. Nature 173, 318.
Crick, F.H.C. 1958. On protein synthesis. Symp. Soc. Exp. Biol. 12, 138–163.
Hoagland, M.B., Stephenson, M.L., Scott, J.F., Hecht, L.I., and Zamecnik, P. 1958. A soluble ribonucleic acid intermediate in protein synthesis. J. Biol. Chem. 231, 241–257.
By five years after the announcement of DNAs structure, workers had made steps into the all important “how are proteins made” problem. Proteins run the body, so knowing how they come about is vital to understanding a cells function and in turn a bodies functioning.
It wasn’t until 1961, that the messenger RNA (mRNA) function was discovered. Here is a series of prominent papers on mRNA function. FYI; mRNA was named by Jacob and Monod.
Brenner, S., Jacob, F., and Meselson, M. 1961. An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 190, 576–581
Gros, F., Hiatt, H., Gilbert, W., Kurland, C.G., Risebrough, R.W., and Watson, J.D. 1961. Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature 190, 581–585.
Jacob, F. and Monod, J. 1961. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318–356.
Then leave it to James Watson, co-discoverer of the DNA structure, to sum up what was know in the journal Science.
Watson, J.D. 1963. Involvement of RNA in the synthesis of proteins. Science 140: 17–26.
Now I’m going to take a massive time leap. The number of papers that were published on DNA, RNA, and their workings is staggeringly large, but the next huge advance came in 1984.
1984: Kary Mullis invented polymerase chain reaction (PCR), a method of amplifying very small amounts of DNA. Why was this a big deal, well, in order to study (and use) DNA you must make a lot of it. This advance, an artificial way to make copies of DNA, allowed the study of these molecules easier, and cheaper.
More leaps in time.
1989, other researchers had found a way to utilise PCR to generate mRNA from scratch, by amplifying DNA strands and using an enzyme called RNA polymerase to create mRNA molecules from these strands.
Then another big advance, transferring the information in the DNA (or RNA) into the body (of a mouse).
1990 Direct gene transfer into mouse muscle in vivo
J A Wolff , R W Malone, P Williams, W Chong, G Acsadi, A Jani, P L Felgner.
As they state on their paper: “RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects.”
Did you get that, by injecting DNA or RNA into a mouse muscle they caused the mouse’s cells to express (make the protein) the recipe contained in the DNA or RNA molecule. They used luciferase, a molecule that gives off light (bioluminescence), to enable them to know that it worked.
More time leaps, and thousands of studies later.
1995 Improved cationic lipid formulations for in vivo gene therapy
P L Felgner, Y J Tsai, L Sukhu, C J Wheeler, M Manthorpe, J Marshall, S H Cheng. (Not the full citation)
One major problem with injecting DNA or mRNA into a body is that the body immune systems detects it, notes that it foreign, and destroys it. In order to allow the expression of sequence/gene desired the molecule needed to be house in a protective coating. These folks managed to do that in a lipid “box” which allowed protection, but also allowed it to fuse with the cell membrane, also mostly lipid, thus transferring the box contents in to the cell.
Another time-leap, and thousands more papers.
2005: Karikó and Weissman published a study announcing a specifically modified form of mRNA, which replaced Uridine with an analog – a molecule which looked the same, but did not induce an immune response.
Katalin Karikó, Michael Buckstein, Houping Ni, Drew Weissman. 2005. Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity 23: 165-175.
Karikó and Weissman, if you’re still awake after reading this, are the researchers I mentioned at the beginning. They began the development of mRNA vaccines for BioNtech
Some other scientists were paying attention. Derrick Rossi, read Karikó and Weissman’s paper and went, hey this should work:
In 2010, Rossi co-founded a biotech company called Moderna, with a group of Harvard and MIT professors, with the specific aim of using modified mRNA to create vaccines and therapeutics.
By 2014, Karikó and colleagues showed that mRNA could be used effectively:
USahin, K Karikó, Ö Türeci. 2014. mRNA-based therapeutics-developing a new class of drugs. Nature reviews Drug discovery 13: 759-780.
2017, Moderna began developing a potential Zika virus vaccine, while in 2018 BioNTech entered into a partnership with Pfizer to develop mRNA vaccines for influenza.
These companies were thus primed to speedily make mRNA vaccines for the RONA.
And the work went on…
2018: Keener AB. A new class of therapeutics instruct the body to make its own drugs. Nature Medicine.
..and goes on: I will not go into the massive number of papers that have been published, and pre-published concerning Covid-19 directly. The number is mind-boggling. Consider this, in October a group of researchers published a review of “the first 10,000” Covid-19 papers. They note that there are more than 100 new papers every day, and since this publication the numbers seem to have increased, with several thousand each week.
Here is that citation:
Anna Odone, Sandro Galea, David Stuckler, Carlo Signorelli, the University Vita-Salute San Raffaele COVID-19 literature monitoring working group, The first 10 000 COVID-19 papers in perspective: are we publishing what we should be publishing?, European Journal of Public Health 30: 849–850.
We are still in the dark Covid-19 tunnel, but some light has appeared at the end.
Wear a mask, stay back, and stay safe.