COVID-19 Vaccine Timing: What’s the Optimal Point in Pregnancy for Passively Immunizing Your Fetus with Maternal IgG?

Here on The Pulse, we have devoted a good amount of time discussing passive immunity. In the context of pregnancy and neonatology, passive immunity is the phenomenon in which the perinate —the fetus prior to birth, the neonate after birth— receives protection against disease-causing agents by way of maternal antibodies. This means that getting vaccinated while you’re pregnant is good for you and for your baby. Generally, only ‘live attenuated’ vaccines are contraindicated in pregnancy. When it comes to vaccination against SARS-CoV2 (the virus that causes COVID-19), none of the vaccines that we’re discussing are live attenuated, meaning that they do not multiply within your body. But, if vaccination against SARS-CoV2 is good during pregnancy, what about the timing of such vaccination? Honing in on the optimal time for receiving a vaccine dose against SARS-CoV2 is the point of our discussion today.

Also called immunoglobulins, antibodies are molecules produced by the immune system. They are produced by B lymphocytes, particularly by mature forms of B lymphocytes called plasma cells. Each plasma cell produces a particular antibody that recognizes a particular portion of an antigen (an entity that provokes and immune response), called an epitope, so each antigen has many epitopes. There are different flavors of antibodies, three of which —IgA, IgM, and IgG — are important to a discussion about how receiving a vaccine dose —either primary series jabs and booster jabs— during pregnancy can help to protect your new baby.

IgA and IgG are flavors of immunoglobulin that typically are released as part of body secretions, including saliva and breast milk. This is one of the reasons why breastmilk helps protect newborns against infectious disease during the first several months of life, during which the baby is not yet ready to receive certain vaccines. IgG also is present in the blood, as is IgM, but IgG can pass between maternal and fetal blood in the placenta, whereas IgM antibodies travel in blood connected in groups of five (pentamers), which are too big to get through the placental barrier.

IgG and IgM antibodies able to recognize particular epitopes of particular antigens are present increasingly in blood after a person is exposed to that antigen. After a second exposure to the same antigen, B lymphocytes that make that make antibodies divide to produce plasma cells, resulting in more IgM and IgG antibodies. Such immune responses are dominated initially by IgM but over time there is increasingly more IgG.

The fact that IgG can pass through the placenta to the fetus can be a good or bad thing. In the case of Rh maternal-fetal incompatibility —the mother’s red blood cells are Rh negative, while the baby’s are Rh positive— IgG antibodies are a problem, because they attack fetal red blood cells. But good IgG antibodies, like those that your B lymphocytes make due to vaccination against SARS-CoV2, also get through. This is an example of passive immunity.

In the middle of 2022, an important study that was publicized by the American College of Obstetrics and Gynecology, researchers found something very interesting. Women who received the two doses of the primary series of a the Pfizer-BioNTech COVID-19 vaccine during weeks 17-30 of pregnancy were compared with women who received their booster shot (3rd dose) during that same part of pregnancy. Basically, we are talking about the middle of pregnancy. The study found that both maternal IgG antibodies and infant IgG antibodies against SARS-CoV2 were higher in cases when the mother had received the third dose in the middle of pregnancy than in cases when the mother had received the primary series during that time period.

Meanwhile, recently, there was a small study published showing that women vaccinated near the end of pregnancy against SARS-CoV2, or just after pregnancy, had IgG lasting for long periods in their breast milk, but IgA levels in their milk dropped off quickly.

As for what this means for the timing of your shots, first of all, when it comes to lactation, in the case of SARS-CoV2, it means that IgG is the issue more than IgA. To have high levels anti-SARS-CoV2 IgG antibody in your milk, at minimum you should be finished with the second shot of the vaccine primary series (first two doses) by two weeks before you deliver. However, if you receive the second shot four to six weeks before you deliver, the levels of IgG in your milk will be as high as they can be when the neonate first starts to nurse. At the same time, the peak levels of IgG antibodies in your blood near the end of pregnancy also means that the neonate blood will have received the highest possible amount of IgG antibodies from your blood, prior to birth. Consequently, if you have never been vaccinated against SARS-CoV2 and you are pregnant, you should aim to receive the second shot of an mRNA COVID-19 vaccine around week 34 of pregnancy, if you have an uncomplicated singleton pregnancy. If you have twins, you should get that second dose by around week 28.

While you are permitted to have an interval of just 3 weeks for Pfizer and 4 weeks for Moderna between the two doses of the primary series, there are good reasons why waiting up to 8 weeks is better. Consequently, if you have a singleton pregnancy and have never been vaccinated, from the perspective of passively immunizing the baby, the optimal time to receive your first vaccine dose is around week 26 of gestation, which falls within that 17-30 week period of the research study that we discussed earlier. Since IgG antibodies persist in the baby only 6-12 months, passive immunity will end sooner if your shots are much earlier in pregnancy. However, you also need to consider that the shots are to protect you against developing severe COVID-19, should you be exposed to the virus. If you develop COVID-19 while pregnant, that’s bad for you and for the fetus. All of this applies, of course, to someone who has not yet been vaccinated by the time that she is pregnant.

If you have been vaccinated with the primary series, the issue then becomes when to receive your booster, which really means your third dose. Based on the research and all that we have just discussed, we know that 17 to 30 weeks will give the fetus the highest possible levels of IgG in her blood. Pushing the time forward by a few weeks however, such as to week 34, should still provide the highest possible level of passive immunization and it will put IgG into the milk, but it will also add a few weeks to how long the IgG persists in the newborn blood. As for a fourth dose, if you are so inclined to receive it and you have not had an exposure for a while, the same concept applies. Aim for it being several weeks before you deliver, in order to maximize the passive immunity.

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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