A model showing the protective effects of intestinal parasites against respiratory syncytial virus in infants may inform prevention strategies, according to new research presented at a global conference sponsored by the Respiratory Syncytial Virus Foundation.

Infant immunity to respiratory syncytial virus (RSV) is affected by maternal microbiota and environmental exposures during pregnancy, Krist Antunes Fernandes, PhD, of Pontifical Catholic University of Rio Grande do Sul, School of Medicine, Porto Alegre, Brazil, and colleagues wrote. However, exposures that historically influenced maternal and infant microbiota, notably intestinal parasites, have mainly disappeared in modern society, they said.

The researchers used a mouse model involving chronic, subclinical Heligmosomoides polygyrus (a common mouse intestinal parasite) infection prior to pregnancy to examine the impact of helminth-enriched microbiota on RSV susceptibility and RSV immunity in offspring.

In the mouse model, the researchers assessed which microbes or chemical mediators passed from mothers might affect offspring health. The researchers also tested the protective effects of supplementation with indole-3-propionic acid (IPA), a metabolic produced by intestinal bacteria, as a way to strengthen the intestinal barrier.

Overall, the parasites protected offspring against RSV, the researchers found. Specifically, “cross-fostering and germ-free transfer experiments identified the vertical transmission of helminth-altered microbiota, independent of maternal antibodies, as the protective driver,” they wrote. In addition, metabolomics data identified IPA as a circulating mediator that was enriched in helminth-altered microbiota.

The researchers then assessed the relevance to humans using bronchial epithelial cell cultures and metagenomic data from helminth-colonized Indigenous populations. In both human and mouse models, IPA inhibited in vitro replication of RSV by stimulating type I interferon (IFN-I) production. In addition, the researchers found that neonatal oral IPA supplementation protected against both RSV and influenza by stimulating IFN-I production.

“Maternal helminth infection durably protected offspring against RSV from weaning to adulthood, reducing weight loss, lung viral titers, and inflammation,” the researchers wrote. However, neonatal oral IPA supplementation reproduced the epithelial IFN-I signature and conferred protection against both RSV and influenza virus. In the human cultures, metagenomic profiles of chronically helminth infected-individuals showed enrichment of IPA-associated tryptophan metabolic pathways and organisms capable of IPA production.

The findings were limited by the use of an animal model, the researchers said. However, the identification of a maternal helminth-microbiota-metabolite axis that protects against RSV highlights the need for an alternative strategy to enhance help protect infants, they noted.

“Harnessing safe microbial metabolites, such as IPA, offers a translational strategy to enhance infant antiviral readiness and reduce the RSV disease burden,” they concluded.

Implications for Enhancing Immunity

Globally, RSV causes approximately 33 million episodes and more 100,000 deaths each year in children younger than 5 years, with the highest burden in the first 6 months of life, said Julia Burger, MD, a pediatrician at Temple Health and associate professor of clinical pediatrics at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“Preventative measures have been restricted to expensive monoclonal antibodies for infants,” Burger told Medscape Medical News. “Understanding how maternal environmental exposures, in this case maternal helminth infection, influence offspring immunity could reveal more accessible preventive strategies, which is particularly important given that over 95% of RSV deaths occur in low- and middle-income countries,” she said.

The findings in the current study align with emerging evidence on the impact of maternal microbiota on offspring immunity, but several aspects stand out, said Burger. “The lasting protection from weaning to adulthood is remarkable, suggesting immune system programming rather than temporary protection,” she said. “The identification of indole-3-propionic acid (IPA, a tryptophan metabolite, and the demonstration that neonatal IPA supplementation alone could confer RSV protection, is particularly important,” she added.

The use of a mouse model is a key limitation of the study, as it may not fully replicate human RSV pathophysiology or gut microbiome-immune system interactions, Burger told Medscape Medical News. However, the results suggest that microbial metabolites such as IPA could represent a new strategy to enhance infants’ immune response to RSV infection, she said.

“In the future, the safety and optimal dosing of IPA supplementation in human infants would require clinical trials,” Burger noted. “The effects of IPA supplementation on vaccine responses and normal immune development also need to be understood before widespread supplementation could be implemented,” she added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Burger had no financial conflicts to disclose.