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Since the beginning of our COVID-19 discussions in the early weeks of this calendar year, we have touched on various aspects of the biology of SARS-CoV2 (the virus that causes COVID-19), its pathophysiology (the way that it causes disease in those who become infected), treatments, and the quest for vaccines. Now, with the end of the year approaching, with more than 55 million cases and more than 1.3 million deaths from the virus documented worldwide, and with the numbers still rising alarmingly in many locations, including in many US states, there is at least some light visible at the end of the tunnel. Recently, it has been announced that two vaccines —one developed by Pfizer and a German biotechnology company called BioNTech, the other by Moderna— have produced encouraging results in clinical trials, while other results are expected in the weeks to come from companies working on still other COVID-19 vaccines. In this post, we’ll discuss the Pfizer-BioNTech vaccine and the Moderna vaccine, since the announcements came out within about a week of one another and also because both vaccines work through the same strategy; they are made of a molecule called mRNA, a chemical that we have discussed in previous posts. Later, as more information comes out on the other vaccines being tested, we’ll have posts devoted to those.
The various vaccines that look promising to be effective and available to massive amounts of people in the upcoming year are all in phases of clinical testing known as phase 2 and phase 3. Sometimes overlapped or conducted in the same study, phases 2 and 3 focus on determining how effective a vaccine is at doing what is designed to do —either stopping a disease from spreading or at least preventing or reducing symptoms in those who do become infected. This is in contrast with phase 1, in which only the safety of a vaccine is studied (although safety continues to be studied throughout phases 2 and 3). One thing that may frustrate you as a mother-to-be is that, like most vaccine trials, the clinical trials of the handful of vaccines that have been developed for COVID-19 have not been including pregnant women among the test subjects. This is despite the fact that there have been proposals to include pregnant women at least in phase 3 testing, not only to verify that the vaccines are safe specifically in the pregnancy setting, but also to determine if the findings on vaccine effectiveness in non-pregnant volunteers applies to pregnant women, or if the dosage (how much vaccine in each shot) or the timing of shots (amount of time between shots) needs to be tweaked for pregnant women.
Generally, what has happened in the history of vaccines is that evaluation of a vaccine in pregnancy is carried out more informally and after the vaccine has already been approved for massive use. Probably, something like this will happen with the COVID-19 vaccines; vaccination will be recommended for pregnant women based on more than a century of experience suggesting that only live vaccines —vaccines in the form of an infectious agent that has been weakened in its ability to cause disease or that causes non-lethal disease, but is still infectious in that it will multiply in body cells— present any serious danger to an embryo or fetus. In the case of the COVID-19 vaccines, we are talking about strategies that are very high-tech compared with the old strategy of taking the actual disease causing agent and changing it in a way to weaken it. Instead, the various COVID-19 vaccines all involve selected molecules that the SARS-CoV2 virus has on its surface like a coat and getting those molecules produced on the surface of something else. This causes your immune system to learn to recognize it without your body ever being in danger of developing COVID-19 disease while the immune system goes through the learning process. With most of the promising COVID-19 vaccines, the surface molecule that we’re talking about is the notorious spike protein, the molecule that gives the virus its crown-like, or corona, appearance when viewed with electron microscopy and also that enables the virus to attach enter your cells by attaching to a protein called ACE-2 that is naturally present on the surface of many types of body cells.
In today’s post, we’re talking specifically about the vaccines of Pfizer-BioNTech and Moderna. In both cases, the business end of the vaccine is a strip of mRNA, which carries the recipe, the instructions, for building the spike protein. In both vaccines, the mRNA is enclosed in a spherical particle made of special molecules that allow the particle to dissolve in water so that it can be injected into the bloodstream, keeping the mRNA cargo healthy until the carrying particle reaches one of your cells, into which it delivers the mRNA. The ability to enclose the mRNA in such particles is vital, because naked mRNA would not last very long inside your blood, where enzymes would break it apart before it has done anything. Once inside a cell, however, the mRNA meets up with a structure called a ribosome, which has machinery that reads the particular sequence —the instructions— of that mRNA and consequently builds the spike protein, which then is transported to the surface of the cell, which it stimulates the immune system. Is this dangerous? The answer is no, because the cells themselves have the enzymes that soon break apart the mRNA so the effect is very short lived. A nurse gives you a shot that sends numerous spherical particles, each containing numerous molecules of mRNA, through the bloodstream to body cells. This causes cells to make spike protein and to display the protein on their surfaces, but soon the mRNA is destroyed and the protein itself cannot be replaced when it too breaks down. This gives your immune system an initial exposure to what looks like the SARS-CoV2 virus, but isn’t. Then, you must get a second shot. With the Pfizer-BioNTech vaccine, that second shot is 21 days later; with the Moderna vaccine, the second shot is 28 days later. Since the immune system has been primed, the response to the second shot is greater than the response to the first and your immune system is then ready to confront the virus in the event that you are exposed.
Based on reports from the companies themselves —reports that must be verified when study data are analyzed and published in peer reviewed articles— the Pfizer-BionTech vaccine is 90 percent effective at preventing symptomatic COVID-19, while the Moderna vaccine is 94.5 percent effective. These numbers represent enormously high effectiveness and suggest that the vaccines should be administered on a large scale, but one big thing that health officials really still want to know is whether and how much these 90 percent and 94.5 percent numbers translate into effectiveness in keeping an infecting person from spreading the virus to others. In other words, experts want to know whether these vaccines produce sterilizing immunity, meaning that they don’t only keep you from getting sick, but actually stop the virus from reproducing inside the body, and in doing so keep the vaccinated person from ejecting virus particles into the air in spit particles. So stay tuned. As time goes on, as information on the effect of these vaccines on infectiousness comes out, we shall discuss it, plus we’ll also be discussing the other COVID-19 vaccines and how they work. These include the vaccine produced by the company Astra-Zeneca and Oxford University, for which an announcement is expected very soon.