Vaccination Against COVID-19 Won’t Harm the Placenta nor Cause Infertility

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Health myths have been rampant in our society since the days when medicine first started to operate based on scientific principles, as have fears of biomedical technology. This trend has continued into the COVID-19 era, a time when fears of vaccination persist, even as government health authorities and the biomedical industry ramp up efforts to get our populations immunized against this horror of a disease. Of the many alarmist concerns that have been circulating concerning COVID-19 vaccines, particularly the Pfizer/BioNTech vaccine against SARS-CoV2 (the virus that causes COVID-19) and to some extent the Moderna vaccine against the same virus, one strikes home on The Pulse: that COVID-19 vaccines, especially the mRNA vaccines, and among those particularly the one made by Pfizer and BioNTech could possibly trigger what doctors call abruptio placentae. That’s Latin for placental abruption, meaning premature detachment of the placenta from the uterus. By way of the same mechanism, those who have speculated that such vaccines could trigger abruptio placentae also worry that the vaccines could cause combination male-female infertility. The idea is very speculative and clinical data, thus far, do not support it, whereas the severely symptomatic COVID-19 surely does place a pregnant woman and her fetus or embryo at elevated risk. So let’s unpack the claim in context of the beautiful world of biology.

One common way that you may encounter the concern is with an introduction along the lines of “The Pfizer vaccine contains syncytin-1, a type of spike protein”, after which the article, or person, will say something like, “So the vaccine will teach the female immune system to attack syncytin-1 on the woman’s own placenta, causing her to lose her placenta and fetus.”

Also called a fusion protein, because it keeps cells fused to one another, syncytin-1 is indeed a protein that is vital to the placenta, and functions similarly to the coronavirus spike proteins that make the viruses sticky. But the viral spike protein is a much larger protein, consisting of three identical units that are made by coronaviruses, including SARS-CoV2, that are assembled into a triple-unit protein present in the protein coat that surrounds the virus particles. The spike protein is present in many copies on the surface of the virus, from which the proteins project outward. Along with giving the virus its crown-like, or coronal, shape when viewed with electron microscopy, the spike protein is what the virus uses to attach to the surface of human cells, so it is tempting to compare the spike protein with syncytin-1, given its role in sticking cells together. The spike protein on SARS-CoV-2 attaches to a human cell surface protein called ACE-2, or the ACE-2 receptor. This allows the virus to enter the cell, where it hijacks the cell’s machinery, producing little baby virus particles that go on to infect more cells. Additionally, by distracting the ACE-2 receptor from its day job, the SARS-CoV-2 virus causes a range of other effects, such as inflammation and disruption of the blood clotting system. On top of this, in some people, infection with SARS-CoV-2 disrupts the different components of the immune response and the timing of those responses, leading to blunting and slowing of the process called adaptive immunity, through which the immune system normally learns how to recognize a new virus, while speeding up what’s called the innate immune response. These two effects show up on blood tests as a decrease in the number of special white blood cells called lymphocytes and a rise in the number of other white blood cells, called neutrophils, and show up clinically as what doctors call cytokine release syndrome. Together with damage to lung tissue resulting from the infection, this can lead to a severe lung condition called acute respiratory distress syndrome (ARDS), a main reason for why a person with severe COVID-19 needs to be put in a ventilator.

All of the above was to show you that the spike protein on the SARS-CoV-2 virus is bad, but for the same reasons the spike protein also makes an excellent tool for producing immunity. That’s the basis of the COVID-19 vaccines that have been in the news and discussed in The Pulse –the vaccines from Pfizer/BioNTech, Moderna, AstraZeneca, and Johnson and Johnson. But as noted above, the spike protein is not the same thing as syncytin-1, so let’s unpack this part a little further.

Proteins are made of building blocks of amino acids linked together. A protein has a particular sequence of amino acids, a sequence that, in turn, is encoded by a sequence of genetic building blocks, meaning building blocks of DNA, or of RNA. DNA is the genetic material that stores your genome. Each chromosome is a very long strand of DNA, with some proteins mixed in, but the DNA component contains the genetic information. RNA also carries genetic information. In the case of many viruses, including coronaviruses, RNA is the only molecule that stores the genetic information; such viruses do not have DNA (although certain other viruses do). In the case of human cells, however, while RNA is not the long-term storage molecule for your genes, it serves a variety of roles related to using the information from your DNA to make proteins. To make a protein from any given gene within your DNA, the DNA sequence of that gene is copied, or transcribed, into a strand of a type of RNA called messenger RNA (mRNA), which is transported out of the nucleus of the cell, into the cytoplasm, where that newly transcribed RNA sequence is read, or translated, into the sequence of amino acids that makes it the particular protein that is encoded. 

Now, in the Pfizer/BioNTech and Moderna vaccines, the business end of the vaccine is in fact a strand of mRNA – mRNA carrying the recipe, not for one of your own proteins, but for the spike protein. And it just so happens that a small portion of the spike protein resembles syncytin-1, which not only is vital for the placenta, but also, because it sticks cells together, is involved in fusion between male and female gametes (sperm and egg) during conception. Based on this, researchers have speculated that the immune response provoked by getting other body cells to make and display the spike protein on their surfaces would cause collateral damage in the form of placental abruption and also might cause infertility. In both cases, we are talking about failure of a cell-to-cell attachment system.

But here’s the problem with that idea: The section of the spike protein in question is not similar enough to syncytin-1 for there to be what immunologists call epitopes (particular immune-generating regions) that would cause an immune reaction against syncytin-1. The dissimilarity would be particularly noteworthy when the spike protein is displayed attached to special other proteins, called MHC receptors, on the surfaces of cells that receive the vaccine mRNA, and that’s exactly what happens; the mRNA goes into your cells, the mRNA is transcribed into spike protein, which then gets transported to the surface of the cell and sits there, attached to either of two types of MHC receptor. The same exact thing happens in the case of COVID-19 vaccines that use DNA, rather than RNA, such as the AstraZeneca/Oxford and Johnson and Johnson vaccines. With the latter vaccines, the DNA payload encodes the same spike protein as the mRNA vaccines encode, but the DNA-containing vaccines require an additional step, namely that the DNA is transcribed into mRNA. From there the process is the same as with the mRNA vaccines; we end up with spike protein on the surfaces of human cells.

Since all of the vaccines produce the same thing –spike protein on the surfaces of body cells, leading to immunity against the SARS-CoV-2 virus—there is not much of a rationale for thinking that one of the vaccines should be more likely than the others to cause immunity against something that is supposed to be in the body, such as the placenta, or gamete cells.  And since the portion of the spike protein that resembles syncytin-1 is not actually identical to that protein, nor is it presented to the immune system in the same way, COVID-19 vaccination —unlike severe COVID-19 disease—is unlikely to cause a severe pregnancy complication, such as abruptio placentae, and unlikely to cause infertility.

 

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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