A respiratory virus that commonly infects infants and young children — and can also be harmful to the elderly — is circulating in the United States. Cases of respiratory syncytial virus, or RSV, have risen higher and earlier in the year than expected from a typical peak in the winter season. By early November, the virus had flooded pediatric wards to such levels as clinicians said The New York Times it was reminiscent of the first surge of the COVID pandemic.
Most children who get RSV have mild cold symptoms, but a fraction become very sick. According to a global estimate, the virus is responsible for around 1 in 28 deaths in children aged four weeks to six months.
No US-approved vaccine exists for this pathogen. But, just as new vaccinations have lowered COVID deaths and hospitalizations, RSV shots would be a welcome tool, capable of preventing future outbreaks. Pharmaceutical giant Pfizer, for example, recently announced that it had promising data in early trials of its protein-based formulation. Pfizer said it plans to submit the single-dose vaccine to the Food and Drug Administration for approval by the end of 2022.
The company says its treatment protects infants during the first six months after birth, but the injections are not intended for babies. Instead, pregnant women would have them at the end of the second or third trimester; the immune defenses their bodies manufacture are passed through the placenta to the fetuses and, later, through breast milk to infants. In this way, the vaccine creates RSV-specific antibodies inside a parent, which then travel through the natural pathways that connect a mother to the child. This potent combination could be part of a growing approach to tackling many viruses capable of harming mothers and their newborns.
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The placenta – the organ that temporarily exists to serve the unborn child in the womb – is a biological mixture of scuba tank and room service: it provides oxygen and nourishment to a growing fetus. It also actively delivers maternal antibodies, especially towards the end of a term. “A full-term baby has a robust load of antibodies that were passed down from the mother during pregnancy,” says Milagritos Tapia, professor of pediatrics at the University of Maryland School of Medicine.
In studies of immunological protection during pregnancy, antibodies — proteins that the immune system uses to mark and signal invaders — get the lion’s share of the attention. Vaccines go the extra mile to trick a person’s body into generating new antibodies against a specific virus. There are other defenses that are passed on to infants, but these are not as easy to measure. “The reason we talk about antibodies is that they are easier to understand and explain,” Tapia explains.
Infant immune systems
Childhood immunity has many nuances. Young children, as the maxim of immunologists goes, are not just small adults whose bodies respond proportionally less to a vaccine. Even after they are born, their immune system continues to develop the ability to produce antibodies. The first vaccines babies receive do not evoke as strong a response as later ones, which is why infant vaccinations against diseases like hepatitis B or poliomyelitis come as a series of three doses. .
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The protection that babies obtain during pregnancy or through breast milk is therefore a palliative measure. Fortunately, these temporary guardians are effective. There is clear evidence that antibodies against RSV are effectively transmitted to children during pregnancy.
In a first-of-its-kind study looking at maternal antibody protections against RSV, Tapia and colleagues followed nearly 600 mother-child pairs in Mali. They measured RSV antibody levels in infants at birth and in umbilical cord blood; higher levels were associated with a significantly lower risk of newborns having a case of RSV in the first three months of life, as shown in a study published in the journal Clinical infectious diseases in 2020. In other words, the more neutralizer babies emerged, the better defended they were in their vulnerable early stages.
“It was what we expected to see,” says Tapia. “Sometimes you have to prove what you think.” It also strongly suggests that “an RSV vaccine given to pregnant women” would protect infants against infection with the virus in infancy, as she and her co-authors write in the paper. Although researchers haven’t studied vaccinations directly, they show that a baby born with lots of antibodies – which come from the parent during pregnancy – is a good sign. Antibodies generated by a maternal vaccine also end up defending the child after birth.
Vaccines given to pregnant women have a precedent. The American College of Obstructions and Gynecologists recommends that pregnant women receive the Tdap vaccine – so nicknamed because it protects against tetanus, diphtheria and whooping cough – between 27 weeks and 36 weeks of gestation, and preferably on the anterior side of this window. The Centers for Disease Control and Prevention also recommend that pregnant women get the flu shot (by injection, not the live form of the virus which comes in the form of a nasal spray). Babies born to those who received maternal flu shots are less likely to get the flu in the first six months of life, studies have also shown.
There is speculation that the COVID quarantines may be responsible for the subsequent spike in RSV cases, as pregnant women encountered the older virus less.
“As nursing mothers were less exposed to common viruses during the COVID-19 pandemic due to preventive measures,” it is expected that “the maternal immune system was not strengthened, resulting in a lower antibody production,” write doctors Hannah Juncker and Britt van Keulen – doctoral student and postdoctoral researcher, respectively, at the Dutch Human Milk Bank – in a joint email to popular science. Junker and Britt are co-authors of a study, published in June in the journal Microbiological spectrumwho found RSV antibodies in breast milk declined six months after the 2020 shutdowns, declining by a factor of 1.7.
Fewer antibodies in breast milk “led to less protection of the breastfed infant”, they write, leading to a “massive epidemic” of RSV in the Netherlands in the summer of 2020.
If this hypothesis – that COVID protections contribute to RSV outbreaks – is confirmed, vulnerability manifests quickly. “It’s one or two seasons where people miss their exposure to RSV and, ka bam!, we are there now,” says Tapia. “It looks like we need regular exposure to these respiratory viruses.”
The current outbreak in the United States, two years after that in the Netherlands, highlights RSV as a global disease. For children under six months old, the virus is the leading cause of pneumonia worldwide. The vast majority of related deaths occur in low- and middle-income countries.
“Not only are more babies getting sick” with RSV in developing countries, “but there are fewer resources to support them through their illness,” says Tapia; some hospitals may not have the breathing machines that the sickest babies need. Even minor cases, which could cause a caregiver in the United States to take a sick day, can have serious consequences in resource-poor countries where, Tapia points out, a parent missing a day of work means their family has hunger. The COVID pandemic has shown that access to vaccines can be extremely unequal; for an RSV vaccine to help globally, it will also need to boost the immune systems of infants in poorer countries.
As Pfizer continues to test the safety and effectiveness of its vaccine, there are ways for pregnant women and those with children to protect themselves against RSV. “These are the same things that kept COVID away,” says Tapia: Washing your hands, wearing masks in crowded places and keeping away from people who are sick or showing symptoms are all ways to stay healthy. health in these times of strong virus epidemic.