Broadly speaking, biologics are products that can be produced only by living systems. This means anything from insulin to vaccines to monoclonal antibodies can be considered a biologic. However, when questions arise about the effects of biologics on newborn responses to vaccines, the focus is on a growing class of medications that target the immune system in the treatment of a broad array of conditions, such as cancer, inflammatory diseases of the colon and lungs, even allergic reactions.
With hundreds of biologics on the market, it is not uncommon for a pregnant woman to receive a biologic during pregnancy. This situation increasingly leads clinicians to ask, “Does maternal receipt of a biologic impact her infant’s vaccine schedule?” Inherent in this question is the fact that many of these medications are monoclonal antibodies with the potential to impact not only maternal immune responses but also those of their infants, particularly because IgG-based monoclonal antibodies cross the placenta just as native maternal antibodies do.
Because some, but not all, biologics affect immune responses, to answer the question, we need to consider a few different factors.
Factor 1: The biologic
First, we need to understand precisely what part of the immune system is impacted by the biologic being used. Typically, a drug formulary or the package insert will have information about the mechanism of action.
If the biologic does not impact the immune system, you have your answer — there would be no concerns about the infant’s vaccinations. If it does impact the immune system and if the biologic is a monoclonal antibody that can cross the placenta, it can impact the infant’s immune system until levels have waned in the infant’s body.
Factor 2: The vaccines
If the biologic is deemed to alter the immune response of the patient and is an antibody that crosses the placenta, we next look at the vaccines in question. What kind of vaccine is needed?
If it is any type of vaccine other than a live, weakened vaccine, the baby can be vaccinated on schedule. While there may be a theoretical or actual risk of a slightly lower immune response to vaccines given while the medication is still present in the infant, three points are important:
- All vaccines given early in infancy require multiple doses to build immunity, and any residual effects from maternal biologic use will decline during that period, so the immune response will become more robust with each dose.
- Even if there was a slightly lower immune response to early doses, it is unclear whether there would be any relevant clinical outcome as the child would still have immunity that would be activated in the event of an exposure.
- If there are any concerns about a less robust immune response during those early months of life, vaccination becomes even more important because vaccines offer a controlled first exposure, compared with natural infection where the same concern about the immune response would come into play.
If the vaccine is a live, weakened viral vaccine, like measles-mumps-rubella (MMR), varicella or rotavirus, the calculation becomes a bit more nuanced. Vaccines administered at 1 year of age or older are beyond the period of concern since maternal antibodies, whether native or from a biologic, diminish during the first six to nine months of life. However, for vaccines given during the first few months of life, like rotavirus — or in some situations, measles-containing vaccine, what do we need to consider? Let’s look at a few potential scenarios:
Question 1: I’m seeing a 3-week-old patient. Her mother has ulcerative colitis and has been receiving vedolizumab infusions every 8 weeks during pregnancy and post-partum. Is there any special vaccine schedule that you recommend for RotaTeq given it is a live vaccine?
Vedolizumab is a monoclonal antibody used to treat conditions characterized by inflammation in the digestive tract. The medication targets a cell surface marker on memory T cells to reduce the movement of white blood cells into inflamed intestinal tissue. Patients using this medication can be vaccinated with inactivated or live vaccines as needed, so it follows that infants of these patients can also safely be vaccinated, including with the rotavirus vaccine.
Because vaccine recipients can shed rotavirus for about a month after receipt of the vaccine, it would be appropriate to counsel good hand hygiene practices since there is still some level of immune suppression in the infant’s parent. However, the risks for any vaccine-associated infection in the parent are minimal given that the virus is weakened. Likewise, the viruses in the RotaTeq vaccine are from a type of the virus that infects cows, so replication levels are lower than for Rotarix, which includes a weakened human strain. Albeit, either rotavirus vaccine would be considered safe to give in this situation.
Question 2: In the event of ongoing community transmission where an infant might receive a first dose of MMR at 6 months of age instead of waiting to receive the first dose at 12-15 months of age, is it safe to vaccinate if mom was on Humira (adalimumab) during pregnancy?
Adalimumab is an IgG1 monoclonal antibody that works by reducing inflammation. It specifically blocks the activity of tumor necrosis factor-alpha. This is a cytokine that is important in the immune response. People who receive this medication should not receive live, attenuated viral vaccines. The medication half-life is two weeks, and it is generally out of a person’s system completely in three to five months. If any amount of adalimumab crossed the placenta, reaching the infant, by the time they are 6 months old, the medication would be gone, so they could safely receive an early dose of MMR vaccine.
Keep in mind that earlier in this infant’s life, rotavirus vaccine is due. While this is also a live, attenuated viral vaccine, it can be safely administered to the infant even before the adalimumab has completely left the infant’s system. This is because the rotavirus vaccine is given by mouth and elicits an immune response at the intestinal mucosal surface. Humira, while present in the infant’s bloodstream, would be unlikely to interfere with that response.
Question 3: I have a 1-year-old patient coming in for MMR vaccine. The infant’s mother is on a biologic for rheumatoid arthritis — she has not told me which one. When I see the family, are there certain classes of monoclonals I should be aware of before vaccinating the infant?
Babies who will be around people on biologics that may impact their immune system can still receive their necessary vaccines, including live, weakened viral vaccines, like MMR and varicella vaccine. In fact, it is recommended that household members of people who are immune compromised receive vaccines on time to aide in cocooning the individual in the household, whether that person is receiving a biologic, cancer therapy, or immunosuppression therapies due to an organ transplant, or have a primary immunodeficiency.
Question 4: I have a 6-month-old patient born to a mom who was not immune to measles virus and received measles immunoglobulin during her fifth month of pregnancy due to a measles exposure. Measles continues to circulate in our community. When would it be appropriate to vaccinate the infant?
Immunoglobulin (IVIG) is pooled human blood plasma from healthy donors. In this case, the blood samples used would have been selected to ensure high levels of measles antibodies in the final preparation.
If a pregnant woman receives measles IVIG during pregnancy, she will pass measles-specific antibodies to her infant in the same way she would pass along her own antibodies. As the IVIG received by the mother would likely have waned between her fifth and ninth month of pregnancy, she likely will pass an ever-diminished amount of measles antibody to the infant compared to a mother with her own circulating immunity — though this has not been well studied. Since any antibodies that crossed the placenta, regardless of their source in the mother, will wane over time, this baby can be vaccinated using the same approach that would be used for an infant whose mother did not receive IVIG. This includes early measles vaccination if the baby is recommended for such due to living in or going to an area with an outbreak. Notably, this early dose would not be counted toward the child’s complete series, so they would need to be vaccinated again at 12 months of age and at 4-6 years of age.
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Broadly speaking, biologics are products that can be produced only by living systems. This means anything from insulin to vaccines to monoclonal antibodies can be considered a biologic. However, when questions arise about the effects of biologics on newborn responses to vaccines, the focus is on a growing class of medications that target the immune system in the treatment of a broad array of conditions, such as cancer, inflammatory diseases of the colon and lungs, even allergic reactions.
With hundreds of biologics on the market, it is not uncommon for a pregnant woman to receive a biologic during pregnancy. This situation increasingly leads clinicians to ask, “Does maternal receipt of a biologic impact her infant’s vaccine schedule?” Inherent in this question is the fact that many of these medications are monoclonal antibodies with the potential to impact not only maternal immune responses but also those of their infants, particularly because IgG-based monoclonal antibodies cross the placenta just as native maternal antibodies do.
Because some, but not all, biologics affect immune responses, to answer the question, we need to consider a few different factors.
Factor 1: The biologic
First, we need to understand precisely what part of the immune system is impacted by the biologic being used. Typically, a drug formulary or the package insert will have information about the mechanism of action.
If the biologic does not impact the immune system, you have your answer — there would be no concerns about the infant’s vaccinations. If it does impact the immune system and if the biologic is a monoclonal antibody that can cross the placenta, it can impact the infant’s immune system until levels have waned in the infant’s body.
Factor 2: The vaccines
If the biologic is deemed to alter the immune response of the patient and is an antibody that crosses the placenta, we next look at the vaccines in question. What kind of vaccine is needed?
If it is any type of vaccine other than a live, weakened vaccine, the baby can be vaccinated on schedule. While there may be a theoretical or actual risk of a slightly lower immune response to vaccines given while the medication is still present in the infant, three points are important:
- All vaccines given early in infancy require multiple doses to build immunity, and any residual effects from maternal biologic use will decline during that period, so the immune response will become more robust with each dose.
- Even if there was a slightly lower immune response to early doses, it is unclear whether there would be any relevant clinical outcome as the child would still have immunity that would be activated in the event of an exposure.
- If there are any concerns about a less robust immune response during those early months of life, vaccination becomes even more important because vaccines offer a controlled first exposure, compared with natural infection where the same concern about the immune response would come into play.
If the vaccine is a live, weakened viral vaccine, like measles-mumps-rubella (MMR), varicella or rotavirus, the calculation becomes a bit more nuanced. Vaccines administered at 1 year of age or older are beyond the period of concern since maternal antibodies, whether native or from a biologic, diminish during the first six to nine months of life. However, for vaccines given during the first few months of life, like rotavirus — or in some situations, measles-containing vaccine, what do we need to consider? Let’s look at a few potential scenarios:
Question 1: I’m seeing a 3-week-old patient. Her mother has ulcerative colitis and has been receiving vedolizumab infusions every 8 weeks during pregnancy and post-partum. Is there any special vaccine schedule that you recommend for RotaTeq given it is a live vaccine?
Vedolizumab is a monoclonal antibody used to treat conditions characterized by inflammation in the digestive tract. The medication targets a cell surface marker on memory T cells to reduce the movement of white blood cells into inflamed intestinal tissue. Patients using this medication can be vaccinated with inactivated or live vaccines as needed, so it follows that infants of these patients can also safely be vaccinated, including with the rotavirus vaccine.
Because vaccine recipients can shed rotavirus for about a month after receipt of the vaccine, it would be appropriate to counsel good hand hygiene practices since there is still some level of immune suppression in the infant’s parent. However, the risks for any vaccine-associated infection in the parent are minimal given that the virus is weakened. Likewise, the viruses in the RotaTeq vaccine are from a type of the virus that infects cows, so replication levels are lower than for Rotarix, which includes a weakened human strain. Albeit, either rotavirus vaccine would be considered safe to give in this situation.
Question 2: In the event of ongoing community transmission where an infant might receive a first dose of MMR at 6 months of age instead of waiting to receive the first dose at 12-15 months of age, is it safe to vaccinate if mom was on Humira (adalimumab) during pregnancy?
Adalimumab is an IgG1 monoclonal antibody that works by reducing inflammation. It specifically blocks the activity of tumor necrosis factor-alpha. This is a cytokine that is important in the immune response. People who receive this medication should not receive live, attenuated viral vaccines. The medication half-life is two weeks, and it is generally out of a person’s system completely in three to five months. If any amount of adalimumab crossed the placenta, reaching the infant, by the time they are 6 months old, the medication would be gone, so they could safely receive an early dose of MMR vaccine.
Keep in mind that earlier in this infant’s life, rotavirus vaccine is due. While this is also a live, attenuated viral vaccine, it can be safely administered to the infant even before the adalimumab has completely left the infant’s system. This is because the rotavirus vaccine is given by mouth and elicits an immune response at the intestinal mucosal surface. Humira, while present in the infant’s bloodstream, would be unlikely to interfere with that response.
Question 3: I have a 1-year-old patient coming in for MMR vaccine. The infant’s mother is on a biologic for rheumatoid arthritis — she has not told me which one. When I see the family, are there certain classes of monoclonals I should be aware of before vaccinating the infant?
Babies who will be around people on biologics that may impact their immune system can still receive their necessary vaccines, including live, weakened viral vaccines, like MMR and varicella vaccine. In fact, it is recommended that household members of people who are immune compromised receive vaccines on time to aide in cocooning the individual in the household, whether that person is receiving a biologic, cancer therapy, or immunosuppression therapies due to an organ transplant, or have a primary immunodeficiency.
Question 4: I have a 6-month-old patient born to a mom who was not immune to measles virus and received measles immunoglobulin during her fifth month of pregnancy due to a measles exposure. Measles continues to circulate in our community. When would it be appropriate to vaccinate the infant?
Immunoglobulin (IVIG) is pooled human blood plasma from healthy donors. In this case, the blood samples used would have been selected to ensure high levels of measles antibodies in the final preparation.
If a pregnant woman receives measles IVIG during pregnancy, she will pass measles-specific antibodies to her infant in the same way she would pass along her own antibodies. As the IVIG received by the mother would likely have waned between her fifth and ninth month of pregnancy, she likely will pass an ever-diminished amount of measles antibody to the infant compared to a mother with her own circulating immunity — though this has not been well studied. Since any antibodies that crossed the placenta, regardless of their source in the mother, will wane over time, this baby can be vaccinated using the same approach that would be used for an infant whose mother did not receive IVIG. This includes early measles vaccination if the baby is recommended for such due to living in or going to an area with an outbreak. Notably, this early dose would not be counted toward the child’s complete series, so they would need to be vaccinated again at 12 months of age and at 4-6 years of age.