Overview

RSV stands for respiratory syncytial virus, a common respiratory virus that usually causes upper respiratory illness with mild, cold-like symptoms. For some groups, like infants, RSV can be a severe lower respiratory tract illness. With no licensed vaccine available for babies, there are two options for protection against RSV. One option is a maternal RSV vaccine during pregnancy between 32 and 37 weeks from September through January. The other option is monoclonal antibodies administered to newborns within a week after birth. The vaccine and antibodies for RSV are both relatively newly approved treatments. This episode examines the available research to evaluate the safety and efficacy of these options so you can make an informed decision for yourself and your baby.

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What is a Vaccine?

Let’s first cover some basics to better understand how vaccines work and their risks and benefits.

Traditionally, vaccines use a weakened or killed version of a disease-causing microorganism or parts of it, like its toxins or surface proteins. Vaccines trigger the immune system to produce antibodies against the disease without causing illness. Essentially, the vaccine teaches the body to recognize and fight the disease if it encounters it in the future. In some cases, immunity lasts a lifetime; in others, booster shots may be necessary to maintain protection.

Different types of vaccines stimulate immunity differently. The RSV vaccine is a subunit vaccine that uses specific proteins or pieces of the pathogen to trigger an immune response.

Immunity

Different forms of immunity can result from vaccination:

• Individual immunity occurs when a single person develops immunity after receiving a vaccine.
• Passive immunity occurs when a pregnant mother passes antibodies to her baby through the placenta or later through breast milk, providing the baby with temporary protection. This is a significant reason for recommending vaccines during pregnancy, including the RSV vaccine.
• Herd immunity occurs when a large portion of the population is vaccinated, reducing the spread of disease. Herd immunity is crucial for protecting individuals who cannot get vaccinated, such as those with compromised immune systems, allergies to vaccine ingredients, or babies too young to be vaccinated. Herd immunity only applies to contagious diseases and plays a significant role in preventing outbreaks and eradicating illnesses.

Evaluating Vaccines

I follow a systematic approach and conduct thorough research when evaluating any vaccine or medical intervention. I ask several key questions:

• What are the risks of the illness the vaccine is targeting?
• What is the history of the vaccine?
• What ingredients are in the vaccine?
• How effective is it?
• What are the risks and benefits?

In addition to these general questions, I consider personal factors like my current health status, the likelihood of exposure, where I live, places I may travel to, and the time of year. Answering these questions requires extensive research and critical thinking.

The Controversy Surrounding Vaccines

Vaccines are a complex and often controversial topic. Some professionals dedicate their careers to researching and studying vaccine safety and efficacy. This makes researching vaccines challenging, as it’s easy to come across information that appears unbiased but may ultimately push a pro- or anti-vaccine agenda.

This episode aims to provide an objective overview of the data so you can make an informed decision that’s right for you. If you have additional questions or concerns, it’s always best to discuss them with your doctor or midwife.

The  Role of the Centers for Disease Control and the World Health Organization 

In recent years, there have been growing questions about the reliability of information from organizations like the CDC and WHO and the potential influence of pharmaceutical companies on these organizations. However, it’s important to note that the CDC and WHO maintain some of the most extensive centralized databases for disease statistics.

While these organizations focus on protecting public health on a national and global scale, their guidelines often inform recommendations by bodies like the American College of Obstetricians and Gynecologists (ACOG), which, in turn, influence your healthcare provider’s advice. Ultimately, your primary concern is the safety and efficacy of a vaccine for you and your baby. Understanding the information that informs your doctor’s or midwife’s recommendations will equip you to have an educated conversation with them and help you make the best decision for your pregnancy.

RSV

RSV stands for respiratory syncytial virus, a common respiratory virus that usually causes upper respiratory illness with mild, cold-like symptoms. The upper respiratory tract includes the nose, throat, and upper airways. However, RSV can also cause severe lower respiratory tract illness in some groups, such as infants and older adults. The lower respiratory tract includes the trachea, bronchi, and lungs. An infection in the lower respiratory tract is much more severe.

RSV is spread through contact with the virus, either from droplets from another person’s cough or sneeze or by touching a surface contaminated with the virus. Common symptoms of RSV include runny nose, decreased appetite, coughing, sneezing, fever, or wheezing. In very young infants, symptoms of RSV may also include irritability, decreased activity, or apnea (pauses in breathing for more than 10 seconds).

Most cases of RSV resolve within a week or two. Complications include bronchiolitis and pneumonia. RSV can also worsen other medical conditions such as asthma, chronic obstructive pulmonary disease, or congestive heart failure.

RSV In Infants

A review of the global impact of RSV states that estimates show that RSV is responsible for over 100,000 deaths annually in children under five . Over 45,000 deaths are in children under six months. This makes RSV responsible for 3.6% of all deaths in children 28 days to six months old. 97% of these deaths are estimated to occur in low-income and middle-income countries.

According to the CDC, RSV results in an annual 2.1 million doctor visits, 58,000–80,000 hospitalizations, and 100–300 RSV-associated deaths in children under five. The mortality data is from a study that examined death certificates from 1999 to 2018. I could not track down more recent data on mortality associated with RSV.

RSV disease in early childhood is quite common, with most children experiencing an RSV infection by the age of 2. While many cases are mild, RSV can sometimes lead to complications such as secondary bacterial infections, the inappropriate use of antibiotics, and long-term respiratory issues, including asthma.

Protection From RSV

RSV is most dangerous for older adults, and the CDC recommends adults over 60 have the option to receive a single dose of RSV vaccine. The next group at the highest risk level is infants and young children. No licensed vaccine is available for infants, and there are two options for protection against RSV: a maternal vaccine during pregnancy or preventive antibodies within a week after birth.

The RSV Vaccine During Pregnancy

Like all vaccines during pregnancy, the main goal of the RSV vaccine for pregnant mothers is for the mother to pass antibodies to her baby before birth. The maternal vaccine aims to prevent RSV disease in infants under six months of age.

Official Recommendations

The American College of Obstetricians and Gynecologists and the CDC recommend a single dose of the RSV vaccine for pregnant mothers between 32 0/7 and 36 6/7 weeks from September through January.

RSV season in the continental United States runs from September through March. The seasonality of this illness affects when the vaccine is recommended. The vaccine is unnecessary if you are not between 32-37 weeks between September through January. The timing of administration may be slightly different in areas like Alaska and tropical climates.

If you received the maternal RSV vaccine during the 2023–2024 RSV season, you are not recommended to receive an additional dose during a subsequent pregnancy. However, it is recommended that your baby receives monoclonal antibodies during the 2024–2025 respiratory season. Monoclonal antibodies will be discussed later in this article.

The RSV Vaccine

There is only one RSV vaccine approved for use in pregnant women. That makes comparing your vaccine options easier, but you also have the option to give your baby monoclonal antibodies after birth instead of getting the vaccine during pregnancy. Let’s discuss the vaccine, and then we will examine monoclonal antibodies.

Abrysvo, manufactured by Pfizer, was approved in 2023 as the first RSV vaccine for use during pregnancy to protect newborns and infants against severe RSV disease in the first six months after birth. This bivalent vaccine includes the two strains of RSV responsible for most RSV infections. Thankfully, RSV does not mutate as rapidly as the influenza virus. Unlike flu vaccines, the RSV vaccine is not currently reformulated each season. You can read more in-depth information in the Abrysvo package insert.

Adverse Reactions

The most commonly reported adverse reactions in pregnant individuals were pain at the injection site (40.6%), headache (31.0%), muscle pain (26.5%), and nausea (20.0%).

Safety

Two clinical studies evaluated the safety of Abrysvo in maternal and infant participants. Since this is a relatively new vaccine, most available data is from the clinical trials used for FDA approval. The clinical studies on the RSV vaccine in pregnancy included only uncomplicated, singleton pregnancies. As is common in clinical studies with pregnant participants, mothers considered high risk for any reason were excluded.

Preterm Birth

Both studies observed a higher rate of preterm births in Abrysvo recipients than in the placebo group. In one study, preterm births occurred in 5.3% (6 out of 114) in the Abrysvo group and 2.6% (3 out of 116) in the placebo group. In another, preterm birth events occurred in 5.7% (202 out of 3,568) in the Abrysvo group and 4.7% (169 out of 3,558) in the placebo group. Both studies note that available data are insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.

Other Adverse Events

The clinical studies observed slightly higher adverse events with Abrysvo than placebo, although these differences are not considered statistically significant. There were 10 (0.3%) fetal deaths in the Abrysvo group and 8 (0.2%) in the placebo group. Adverse events in infants from birth to 1 month of age were observed in 37.1% in the Abrysvo group compared to 34.5% in the placebo group. Low birth weight was observed in 5.1% of participants in the Abrysvo group versus 4.4% in the placebo group, and neonatal jaundice was observed in 7.2% in the Abrysvo group versus 6.7% in the placebo group.

A developmental toxicity study was performed on female rabbits who were administered a vaccine formulation containing two times the antigen content of a single human dose of Abrysvo before and during gestation. The study showed no evidence of harm to the fetus or to postnatal survival, growth, or development.

No studies have been conducted on the RSV vaccine during breastfeeding. It is not known whether Abrysvo is excreted in human milk. Data are not available to assess the effects of Abrysvo on breastfed infants, milk production, or excretion.

This vaccine has only been available for about a year; safety monitoring is ongoing. Pfizer maintains a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Abrysvo during pregnancy. V-safe is a health monitoring system for vaccines maintained by the CDC and includes the RSV vaccine.

Efficacy for RSV Vaccine

Typically, an illness starts in the upper respiratory tract, affecting the nose and throat, and can move to the lower respiratory tract, affecting the bronchi and lungs.

Vaccine efficacy for the RSV vaccine was evaluated as the relative risk reduction of lower respiratory tract disease (LRTD) cases and severe lower respiratory tract disease in the control and placebo groups. A positive PCR test and symptoms like fast breathing, low oxygen levels, or chest wall indrawing confirmed cases of LRTD. Severe forms included even faster breathing, lower oxygen levels, need for respiratory support, ICU admission, or unresponsiveness.

The clinical study to evaluate vaccine effectiveness compared approximately 3,500 pregnant women who received Abrysvo to approximately 3,500 pregnant women who received placebo. Within the first 90 days after birth, there were 24 cases of LRTD in the control group and 56 in the placebo group. These figures were used to calculate a vaccine efficacy figure of 57.1%. Efficacy decreased over time, and within 180 days after birth, it declined to 51.3%.

This clinical study showed higher efficacy rates for reducing severe LTRD. Vaccine efficacy within the first 90 days after birth was 81.8%, and within 180 days was 69.4%.

Overall, the vaccine will reduce, but not eliminate, the risk of a baby developing LRTD or severe LRTD. The clinical study acknowledges that vaccine efficacy results met the statistical criterion for success in reducing severe LRTD due to RSV but not for non-severe cases.

Ingredients

Let’s examine the ingredients included in the Abrysvo RSV vaccine. Amounts are per 0.5 mL dose.

• 120 mcg of RSV stabilized prefusion F proteins (60 mcg RSV preF A and 60 mcg RSV preF B). These are the active components targeting two RSV subtypes (RSV A and B) to stimulate immunity.
• 0.11 mg tromethamine and 1.04 mg tromethamine hydrochloride are buffer agents that help maintain pH stability.
• 11.3 mg sucrose and 22.5 mg mannitol are stabilizers that protect the vaccine during storage.
• 0.08 mg polysorbate 80 is a surfactant to help mix the ingredients evenly.
• 1.1 mg sodium chloride to maintain an osmotic balance, similar to bodily fluids
• Each dose may also contain residual amounts of host cell proteins (≤0.1% w/w) and DNA (≤0.4% ng/mg of total protein) from the manufacturing process. The RSV proteins are manufactured using genetically engineered Chinese Hamster Ovary (CHO) cells.

Some concerns about residual host cell proteins and DNA fragments have been raised, including that these could trigger an allergic or a heightened immune reaction. Concerns about DNA fragments stem from a theoretical risk that foreign DNA might integrate into human cells. Still, the DNA in vaccines is highly fragmented and present in minuscule amounts. Additionally, human cells have strong defenses against the incorporation of foreign DNA. Regulatory authorities carefully assess these risks and ensure that any residual DNA in vaccines is at levels far below those that could pose harm. There have been no documented cases where residual DNA fragments in vaccines have caused harm to humans.

Polysorbate 80 is a common stabilizer in vaccines. Concerns about polysorbate 80 primarily revolve around its potential to cause allergic reactions or hypersensitivity, though such reactions are rare. There are theoretical concerns about polysorbate 80 increasing the permeability of the blood-brain barrier, potentially allowing substances to cross into the brain. However, the concentrations used in vaccines are extremely low. This ingredient is not exclusive to vaccines and is also used in many processed foods, cosmetics, and pharmaceuticals.

You could easily find yourself conducting extensive research on each of these ingredients. Remember that they are commonly used in pharmaceuticals, present in tiny amounts, and have all undergone thorough testing to ensure safety.

Combining RSV and Other Vaccines

According to the CDC and ACOG, the RSV vaccine may be given simultaneously with other vaccines routinely recommended during pregnancy. Pfizer did not study the concomitant administration of Abrysvo with other vaccines like Tdap or influenza in pregnant women. However, we do have data on concomitant administration in individuals over 60.

When Abrysvo was administered with a flu vaccine to individuals over 60, 30.0% of participants reported fatigue. This was higher than 19.1% who received Abrysvo alone and 27.1% who received the flu vaccine and a placebo concomitantly. Every vaccine has possible side effects, like pain and swelling at the injection site. It would seem logical that these side effects could be more substantial if you get multiple vaccinations in one visit.

In a study that examined the concomitant administration of Abrysvo and a Tdap vaccine in individuals over 60, the immune response to the pertussis part of the Tdap vaccine was lower than when Tdap was given alone. This was also observed in a separate clinical study for the Tdap vaccine when Tdap and flu vaccines were combined. The point of the Tdap vaccine during pregnancy is for immunity to pertussis.

Despite these findings, the medical community does not see this as significant enough to warrant recommending that the vaccines not be administered during the same visit. While it is pure speculation, and I try to avoid that on the Pregnancy Podcast, the CDC aims to get as many people vaccinated as possible. If you can knock out several vaccines in one visit, more people are likely to get vaccinated than if they are spaced out over multiple visits. In addition, it is possible that advising vaccines not to be administered together could increase vaccine hesitancy.

You have choices regarding which vaccines you opt-in to and when they occur. Talk with your doctor or midwife if you have questions about combining multiple vaccines in one visit.

Monoclonal Antibodies

For mothers who do not get the RSV vaccine during pregnancy, ACOG supports the administration of monoclonal antibodies to infants born during the respiratory season (September-March). Monoclonal antibodies are also recommended if a baby is born within 14 days of the mother getting the RSV vaccine since it takes about two weeks for the maternal vaccine to transfer to infant protection. Vaccines prompt the immune system to produce antibodies. Monoclonal antibodies are essentially pre-made antibodies to target and neutralize specific pathogens. Although monoclonal antibodies do not affect the immune system memory, there is protection as long as the antibodies remain in your system.

Nirsevimab is a long-acting monoclonal antibody used to prevent RSV in infants and some young children at high risk for complications. It is given as an injection at birth or within the first week of birth during the RSV season. Nirsevimab was initially approved in 2023 under the brand name Beyfortus. It was developed by AstraZeneca and distributed by Sanofi Pasteur, Inc. The package insert provides more in-depth information about this treatment.

Ingredients

Let’s examine the ingredients included in the Beyfortus. Amounts are per 0.5 mL dose.

• Nirsevimab-alip (50 mg) is the active ingredient, a monoclonal antibody specifically designed to prevent respiratory syncytial virus (RSV) infection.
• Arginine hydrochloride (8 mg) is a stabilizer that helps maintain the protein structure of the monoclonal antibody.
• Histidine (1.1 mg) and L-histidine hydrochloride monohydrate (1.6 mg) are amino acids that maintain the formulation’s stability and pH.
• Polysorbate 80 (0.1 mg) prevents the active ingredient from clumping. We discussed this ingredient in more detail when discussing ingredients in the RSV vaccine. The monoclonal antibody administration does have a slightly higher concentration of polysorbate 80, compared to 0.08mg in the maternal vaccine.
• Sucrose (21 mg) is a stabilizer and cryoprotectant, helping preserve the monoclonal antibody’s structural integrity during storage.
• Water for injection (USP) is the solvent in which all the ingredients are dissolved. The term USP indicates that the water meets the standards the United States Pharmacopeia sets for purity and safety.

The ingredients are commonly used in pharmaceuticals, present in tiny amounts, and have all undergone thorough testing to ensure safety.

Safety and Adverse Reactions

The most common adverse reactions were rash (0.9%) and injection site reactions (0.3%). Serious hypersensitivity reactions have been reported following Beyfortus administration. These reactions included hives, difficulty breathing, bluish discoloration of the skin, and decreased muscle tone. These are all signs that often accompany anaphylaxis, which is a severe allergic reaction. I could not track down the number of cases of anaphylaxis. Although severe allergic reactions are rare, this is always a risk of any vaccine or pharmaceutical.

Efficacy

A couple of trials evaluated the efficacy of Beyfortus. One trial evaluated medically attended RSV lower respiratory tract infections for infants born at 29-35 weeks. 2.6% of infants given Beyfortus had a medically attended RSV lower respiratory tract infection, compared to 9.5% in the placebo group. These figures were used to calculate an efficacy figure of 70.1%. Efficacy against an infection with hospitalization was 78.4%. A trial of infants born after 35 weeks found that Beyfortus reduced the incidence of medically attended RSV lower respiratory tract infections by 74.9%, and efficacy against RSV with hospitalization was 60.2%.

Making a Decision

You have a few options to protect your baby against RSV. You can opt into the maternal vaccine during pregnancy or give your baby monoclonal antibodies shortly after birth. Like any intervention, these should come with informed consent, which means you can opt out of either or both of these interventions.

Talk to Your Doctor or Midwife 

Hopefully, this article will provide a lot of evidence to help you decide whether the RSV vaccine or monoclonal antibodies are the right choice for you or your baby. Even if you do not have a strong opinion, you should have a basic understanding and confidence to have an educated conversation with your care provider. Please talk to your doctor or midwife about the RSV vaccine of monoclonal antibodies and bring up any questions or concerns.

Thank you to the amazing companies that have supported this episode.