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During the third week of December, the Moderna mRNA vaccine for COVID-19 was endorsed by a review panel in the US Food and Drug Administration (FDA), implying that soon (perhaps already by the time that you are reading this) Moderna will receive the emergency use authorization (EUA) that the Pfizer-BioNTech vaccine received the evening of December 11. This means that the Moderna vaccine will be administered widely through the US population, following in the footsteps of Pfizer-BioNTech.
Meanwhile, although being pregnant or trying to get pregnant has disqualified women from participating in clinical trials of the COVID-19 vaccines, there actually are data on the vaccines in pregnancy, due to some study volunteers getting pregnant after receiving the first or second vaccine dose. As for analysis of those data, Moderna has announced that toxicity studies have revealed no adverse effects from the vaccine in the realm of reproduction and development. In other words, press release data from the company (data that have not yet been scrutinized in peer reviewed studies), suggest that the Moderna COVID-19 vaccine poses no particular maternal or fetal/embryonal risks. Does this mean that the Moderna vaccine is a better choice for pregnant women compared with the Pfizer-BioNTech, or the other COVID-19 vaccines? The answer is not necessarily, because other companies, notably Pfizer-BioNTech are in the process of conducting the same type of study. At the same time, while professional and scientific associations, like the Society for Maternal-Fetal Medicine, have suggested that a woman who knows that she is pregnant should hold off on receiving a COVID-19 vaccine, the same Society for Maternal-Fetal has also recommended that COVID-19 vaccines should be available to pregnant women. On top of that, we need to point out that there is no rationale —no theoretical basis— for why the Pfizer-BioNTech and the Moderna vaccines should be harmful during pregnancy in the first place. Historically, the concern about vaccines and pregnancy has been with live vaccines, meaning vaccines that are themselves an infectious agent similar to the infectious agent that causes the disease, albeit a weakened form of the causative agent. But that’s not the case with these high-tech vaccines that are coming on stage to protect you against COVID-19. How did we get to this point, beginning to vaccinate people against a pandemic that had been around for only a year? A lot has to do with the advanced biotechnology, plus it’s part of a broader question of how a vaccine is tested, so let’s take a peak at that process.
The first thing that researchers do with a vaccine that theoretically should trigger immunity against a certain infectious disease is to test the vaccine in laboratory animals, usually starting with mice. This is called the pre-clinical testing phase and right now there are more than 100 COVID-19 vaccines in this stage. What happens in this stage is that scientists administer the vaccine to the animals in varying dosages and with varying schedules and look for adverse effects and limits of safety. Typically, they also divide laboratory animals receiving the vaccine into groups and infect some of the groups with the agent the causes the disease, in this case with SARS-CoV2, the virus that causes COVID-19. If the animals don’t get sick after being exposed to the virus, this suggests that the vaccine prevents COVID-19 disease. If the animals are not infectious to other animals that suggests the vaccine prevents infection. When safe dose limits are established in laboratory animals and when the pre-clinical studies suggest that a vaccine also is effective, researchers then can apply to elevate the vaccine candidate to clinical testing, meaning to conduct trials on human volunteers. Only a fraction of the vaccines that get through pre-clinical testing make it to this point, but if they do, the first step is a phase 1 trial. In this phase, a few to several dozen healthy human volunteers are given the vaccine with doses that are extrapolated for their size and weight based on the range doses that demonstrated safety and effectiveness in the laboratory animals during pre-clinical testing. The point of phase 1 is to look for adverse effects and do see how dosing and schedule of the vaccine doses affects the severity and likelihood of the adverse effects. If a vaccine passes this stage, demonstrating that it can be tolerated in most people, then Phase 2 testing can begin, meaning that now the vaccine is given to several dozen to hundreds or possibly up to 1,000 volunteers, to see if it is effective in protecting against the disease and infection, and to continue evaluating safety. Since you cannot intentionally expose people to a dangerous disease as scientists do with mice, here the exposure condition is met by selecting a high enough number of people and people from various environments that make it statistically likely that many of them would get exposed to the SARS-CoV2 virus from the community, meaning by accident. In both phase 1 and phase 2, some of the volunteers are given a placebo, a fake vaccine, while others get the real vaccine. The placebo may either be saline without any vaccine in it, or it may be an actual vaccine for a different disease, like a vaccine for meningococcal bacteria, so that it will cause side effects, making it virtually impossible to know that you have the placebo. A vaccine that does well in Phase 2, then goes to Phase 3, where it is tested in a much larger group of people, such as many thousands. These COVID-19 vaccines that we have been discussing here on The Pulse —Pfizer/BioNTech, Moderna, and AstraZeneca/Oxford— have all been through Phase 3 where they have performed impressively. And when the number of volunteers gets as large as it must be for a phase 3 trial, even though pregnancy disqualifies you from participating, there are bound to be women among the volunteers who are unknowingly pregnant when they receive the first dose because they just conceived a day or two before, so the pregnancy test is negative, and there are bound to be women who become pregnant between the first and second shot. Then, once a vaccine has been approved to administer through the general population, eventually it will be approved for pregnant women, as long as study of the effects in women who were pregnant unknowingly in Phase 3 studies have not shown that the vaccine is of particular danger in pregnancy settings.
