We now have three Covid-19 vaccines reporting encouraging early results in Phase 3 trials. Induction of immunity to Covid-19 among vaccine recipients is in the range of 90% for all three vaccines.
The development of Covid-19 vaccines rests on striking advances in the life sciences that have occurred mainly in the last three decades. (See P.S. and P.P.S. for background. Reading an older post, Viruses–an Orientation, might be good for additional perspective. Vaccine! Part I, last Monday’s post, offers historical background on vaccines.)
The two first announced vaccines results were from the companies Pfizer and Moderna. Both of those vaccines are classified as “mRNA vaccines.” The third vaccine, produced by AstraZeneca, whose early results were announced last Monday, is a “chimpanzee adenovirus vector vaccine.” (Incidentally, the Russian vaccine, Sputnik V, is another “adenovirus vector vaccine.”) That vaccine classification obscures a basic fact: All these contenders use the tools of modern molecular biology to stimulate the human body’s immune system to make antibodies to a single component of SARS-CoV-2, specifically the “spike protein.”
The spike protein lives on the surface of the SARS-CoV-2 virus particle. The spike protein is the “corona” of this particular coronavirus. It binds to the outer membrane of our cells, the first step in Covid-19 infection. At least theoretically, a strong antibody response to the spike protein should halt the virus in its tracks.
All the current frontrunner vaccines ultimately depend on offering a specific strand of messenger RNA (mRNA) to the molecular machinery of our cells (see P.S. for detail). That machinery is indiscriminate. It will translate whatever mRNA is presented to it. It doesn’t matter if that mRNA was properly read from the host cell’s DNA or whether it was injected by virus particle (as in Covid-19 infection) or whether it was delivered into the host cell by vaccine technology. Whatever protein(s) the mRNA specifies is what the cell’s molecular machinery turns out.
Note: Unlike nearly all traditional vaccines this modern vaccine technology tries to focus the immune system on neutralizing just one key antigen. That is very elegant, but it is new and different. The ideas have been around at least since the first SARS epidemic in 2003, but because that first SARS virus was quashed in the early stages, these techniques have not been broadly tested in humans until now.
The three current frontrunner vaccines differ in how they present mRNA to the cell’s molecular machinery. The Pfizer and Moderna mRNA vaccines both use the same (or very close to the same) mRNA. Messenger mRNA in its naked state outside of a cell is quickly degraded. These two vaccines differ in the specifics of their packaging and delivery of the spike protein mRNA code, but both vaccines require very cold temperatures to keep the mRNA stable. That makes for some tricky and expensive delivery logistics.
The AstraZeneca vaccine uses a different trick. The coding for the spike protein was reverse engineered from the original RNA code into a string of DNA and spliced into the genome of a wholly different virus. In this case, the virus used is a weakened chimpanzee adenovirus still capable, at a low level, of infecting human cells. The adenovirus becomes the vehicle that carries the spike protein coding (in form of DNA) and injects it (along with rest of the adenovirus genome) into the host cells. There are comparative advantages and disadvantages between this adenovirus vector method and the mRNA method. The AstraZeneca adenovirus vector vaccine, using DNA, is much more temperature stable than the mRNA vaccines–and it is cheaper and easier to make in large quantities. But there are some practical worries. Some folks receiving vaccination might already have antibodies to adenoviruses that could interfere with optimal delivery of the DNA. Moreover, the weakened chimpanzee adenovirus itself may stimulate its own immune response with attendant side effects.
The mRNA vaccines of Moderna and Pfizer are trickier to handle than the adenovirus vaccine of AstraZeneca, but the mRNA vaccines, if properly delivered, seem, at least based on current reports, to offer the best protection. The details of AstraZeneca’s Phase 3 research presentation raised eyebrows already by mid-week, bringing into question the applicability of the early results to older populations. (See After Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine.) Time will tell. All this scrutiny will ultimately bring out the details.
The Food and Drug Administration (FDA) will hold a public hearing on proposed emergency authorization of both the Pfizer and Modena mRNA vaccines on December 10. If approved, distribution of these two vaccines in the U.S. could start by December 13th.
I was recently asked if I trust “the vaccine” for Covid-19. My answer required some contemplation. What I trust is that the scientists toiling in corporate and university laboratories the world over are doing their best to produce vaccines that are safe and effective that will offer us a path out of this pandemic. I trust them regardless of monetary incentives, ethnicity, nationality, and personal egos. There will be side effects that occur with each vaccine–and I could suffer from one just like anyone else might, but I trust the transparent efforts to minimize the number and severity of side effects. I can have a pretty dark view of human nature at times, but I cannot picture a person evil enough to knowingly unleash a vaccine with dire side effects on their fellow humans.
All of that said, although I would like to snap my fingers and go back to my former life, I can endure this isolation a while longer as more and more results come in. As that occurs I am hopeful that confidence will build and by the time a vaccine is actually available for me to use I will be happy to take the small risk of receiving it.
Keep to the high ground,
Jerry
P.S. Molecular Biology Basics: Both RNA and DNA consist of strings (“strands”) of small organic molecules called nucleotides. (Remarkably, both DNA and RNA each use only four nucleotides.) The order of nucleotides in a strand of DNA or RNA is read in sequential chunks of three nucleotides. Each ordered chunk of three nucleotides is call a “codon.” In turn, the order of codons specifies the order of stringing together amino acids (of which only 20 amino acids are used). Those strings of amino acids then fold (by molecular rules) into proteins. Proteins are the primary building material of life on earth.
The coding for the proper stringing of amino acids to make a specific protein can be contained in a segment (a gene) of either DNA or RNA. In non-viral life (like you and me) the flow of information is from the DNA contained in the nucleus of the cell to a complementarily coded messenger RNA (mRNA). That specific mRNA travels from the nucleus to the cell’s cytoplasm. There the mRNA string is read by a macromolecular machine called a ribosome into the specific string of amino acids that will form a protein.
Molecular biologists in the last several decades have figured out how to manipulate the genetic code contained in DNA and RNA, snipping sequences of the code (genes) from DNA and RNA, moving them, and splicing them into other DNA and RNA code strings. That is the substance of “genetic engineering,” the science behind these vaccines and behind all “genetically modified organisms” (GMOs).
P.P.S. An Ode to the Science behind this vaccine development: The pace and the detail of this vaccine effort is absolutely mind-blowing. No previous vaccine has been brought successfully into widespread use in less than four years (ten years is more usual). We are now less than a year into Covid-19 (even if seems like ten…).
If you mentally clear away all the nationalist, paranoid bullshit we’ve been fed the last four years and take a broader world view, it is clear that what we are seeing in the build-up to these vaccines is a world wide scientific collaboration founded on advances in the life sciences and communication that few if any of us fully grasp. In January Chinese scientists sequenced the genome of the virus that causes Covid-19. They published the result in an open forum on the internet and within weeks the scientific community in all corners of the globe set to work on a vaccine. They share information not just on paper but on the internet in real time. By October there were 321 vaccine candidates in development world-wide with 56 of them in clinical trials. As I’ve tried to wrap my head around just the three current frontrunner vaccines I’ve read of work done and connections made in the United Kingdom, Sweden, Brazil, Switzerland, Russia, as well as the U.S. The difference between a collaboration and a conspiracy is that a conspiracy is formed in secret for some nefarious purpose. I refuse to believe that is the case here, although I can begin to grasp the suspicious mindset which tends to assume the worst of human nature and goes to a dark place of the chip implantations and fear of the “New World Order.” Imagining some evil force behind it all is far easier than actually grasping the details of the science and how science works.