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Why Certain Vaccines Are Not Given During Pregnancy

We have been assuring you about the pregnancy safety of the COVID-19 vaccines of Pfizer-BioNTech and Moderna, and others such as Janssen (Johnson and Johnson), AstraZeneca/Oxford, and Novavax, because they do not fall within a category of vaccines that raises concern during pregnancy. This issue is important to unpack, but there are multiple issues. One issue is that there aren’t nearly as many data on both the effectiveness and safety of the approved COVID-19 vaccines in pregnant women as there are data from non-pregnant women, and data from men and children. But given the risk from COVID-19 itself, which tends to have a worse outcome in pregnant women than in women of otherwise equivalent health status and age who are not pregnant, the need for more data has not been a reason for COVID-19 vaccination not to be recommended during pregnancy. It is recommended, and related to this last year we debunked a popular, false claim that COVID-19 vaccines could harm the placenta, or cause infertility. Then, recently, we also debunked popular misinformation regarding the vaccines and fertility. But to have a deeper appreciation for the science and the thinking of experts, it’s important to understand why there are certain vaccines that, despite being safe outside of pregnancy, are indeed not recommended during pregnancy.

Basically the group of vaccines that are considered to be contraindicated in pregnant women are the handful of vaccines that doctors call live, attenuated vaccines. Such vaccines consist either of viruses, or bacteria, and the word live is kind of misleading, when it comes to virus vaccines. That’s because viruses are never alive. They exist on the boundary between living and non-living things, so they cannot be killed. But what ‘live’ means in this case of a live viral vaccine is that it is able to reproduce, able to make little baby viruses, when it infects a cell and takes over the cell’s machinery. In the case of live bacterial vaccine, live means actually alive, although in all cases of live vaccines the entities that are ‘live’ are also attenuated. Attenuated means that the infectious agent used in the vaccine has been altered in a way to weaken it, such that it cannot do the kind of harm to the body that disease-causing version of it does, even though it can reproduce. Often this means that it can reproduce, but not as well as the more potent, disease causing agent that it is designed to teach the immune system to recognize. The most common live vaccines are viruses, notably the measles-mumps rubella (MMR) vaccine, the varicella (chickenpox) vaccine, the oral rotavirus vaccine, and the live attenuated flu vaccine (given as a nasal spray). There is also the live typhoid vaccine, consisting of live, attenuated bacteria, but it is not given routinely in the United States, except in the military.

Because live, attenuated vaccines infect and spread, they are given only to people with healthy immune systems. Now, even though pregnant women usually have healthy immune systems, there is a theoretical risk that any infectious agent that reproduces in a pregnant woman could pass through the placenta and infect the fetus. This does not actually mean that approved, lived attenuated vaccines, like the MMR vaccine, or the chickenpox vaccine, would actually harm a fetus, but they are not given to pregnant women, to be on the safe side.

This brings us to the issue of how the approved COVID-19 vaccines differ from live attenuated vaccines, such as the MMR. One observation that has been a happy surprise among doctors and vaccine workers is how strongly the immune system has been responding to the COVID-19 mRNA vaccines, meaning the vaccines of Pfizer-BioNTech and Moderna. As we have discussed a few times, these vaccines contain a recipe for cells to make a protein, called the spike glycoprotein, or just spike protein for short. The recipe is carried in molecules of messenger RNA (mRNA), a type of genetic molecule similar to DNA, the chemical that carries the genes of each body cell. Although mRNA is genetic material, although the mRNA of the vaccines is actually a gene of the spike protein, the mRNA is kind of gene that has only a very temporary effect on any cell that receives it. The mRNA from the vaccine causes the cell to produce spike protein for several hours, or possibly a day or so, but mRNA does not last long in the cell. There is less and less of it as time goes on.

In terms of what the immune system sees following each vaccine jab, mRNA vaccines are different from live attenuated vaccines, since live vaccines reproduce themselves and spread through the body. This creates a kind of extended target practice compared with the classic kind of vaccine, known as a ‘killed’ vaccine, which does not make sense for a virus, so it is also called an inactivated vaccine. Inactivated (killed) vaccines provide target practice, but do not reproduce themselves.

Now, since the mRNA vaccines do not reproduce themselves, researchers anticipated that they would act more like inactivated (killed) vaccines, or like another kind of vaccines consisting of just protein (called subunit vaccines), than like live attenuated vaccines. For this reason scientists and public health authorities were concerned, at first, that giving just two jabs of the Pfizer-BioNTech or Moderna vaccines, just a few weeks apart, would not produce good long-term immunity. They expected that would have to be additional doses, or at least the first two doses would have to be separated by an interval of at least three months to produce good, long-term immunity. But, in terms of the immune system, the mRNA vaccines seem to be acting more like live, attenuated vaccines. Probably, this is because the target practice that they provide the immune system lasts longer than the target practice that occurs with an inactivated (killed vaccine), or with a vaccine made of just protein. But the rationale for the vaccines being safe during pregnancy is the same for the mRNA vaccines as it is for the old style, inactivated (killed vaccine). Namely, there is no reason to be concerned, since there is no way that the vaccines can reproduce themselves, either in the mother, or in the fetus.

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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