Early RSV infection turns maternal allergy into a powerful driver of childhood asthma

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Dec 8 2025

By combining nationwide health data with elegant immunology experiments, researchers reveal how RSV infection in infancy hijacks maternal antibodies to tip the immune system toward asthma, and why preventing RSV early in life could change the trajectory of allergic disease.

Study: Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life. Image Credit: Art_Photo  / Shutterstock

Previous research suggests that asthma is a complex disease driven by both genetics (hereditary predisposition) and environmental triggers (e.g., viral infections), yet the specific interplay between these factors has remained elusive. In a recent study published in the journal Science Immunology, researchers leveraged both an extensive human dataset (> 1.5 million children) and murine models to address this knowledge gap.

The study revealed a synergistic interaction between two major risk factors: parental allergy or asthma, particularly maternal allergy, and neonatal infection with respiratory syncytial virus (RSV). Specifically, viral infections were observed to manipulate the infant’s immune system to alter the handling of maternally transferred antibodies, inadvertently priming the child for asthma during a critical window of immune development.

Crucially, the study demonstrates that preventing early-life RSV infection in a preclinical model can interrupt this pathogenic cascade, providing a mechanistic proof of concept that early RSV immunoprophylaxis could reduce asthma risk in susceptible children if similar mechanisms operate in humans.

Unresolved Links Between RSV, Heredity, and Childhood Asthma

Decades of research have established a correlation between viral infections during infancy (especially those caused by human respiratory syncytial virus [hRSV]) and the subsequent development of asthma during childhood, but the mechanisms underpinning these associations remain elusive. In parallel, having a parent with asthma or allergic rhinitis is a well-established risk factor for later childhood asthma.

Unfortunately, these observations have resulted in a long-standing “chicken-or-the-egg” debate in which researchers and clinicians are unsure whether severe viral infections cause asthma-triggering immune damage, or whether children with a genetic or allergic predisposition are inherently more vulnerable to severe viral illness, thereby complicating prevention strategies and causal inference.

Furthermore, although it is known that mothers transfer antibodies to their infants to confer early protection, how these antibodies interact with viral infection to potentially alter the child’s long-term immune trajectory remains unresolved.

Dual Human–Mouse Approach to Clarify Mechanisms

The present study aims to address this knowledge gap and inform future pediatric research by leveraging a dual approach that combines large-scale epidemiological data with mechanistic laboratory experimentation.

Childhood asthma data were obtained from the Danish National Patient Registry, a comprehensive dataset covering the entire Danish population. The study included data on 1.5 million children born between 1994 and 2018, recording associations between hospitalizations for hRSV bronchiolitis in the first 6 months of life, parental history of asthma or allergic rhinitis, and the child’s subsequent asthma diagnosis through early adulthood.

To explore causality and elucidate underlying mechanisms, the researchers developed a complementary preclinical mouse model using the pneumonia virus of mice (PVM), a virus closely related to hRSV that naturally infects rodents. Newborn mice born to mothers sensitized to house dust mite (HDM) allergens were infected neonatally with the virus and later exposed to allergens.

Experimental outcomes were assessed using flow cytometry to characterize immune cell populations, single-cell RNA sequencing to map infection-induced transcriptional changes, and flexiVent technology to measure lung mechanics and airway hyperresponsiveness (AHR).

Finally, a maternal immunoprophylaxis strategy using the monoclonal antibody MPE8 to block viral infection, administered to allergic dams prior to neonatal infection, was tested to simulate passive RSV immunization approaches such as maternal vaccination or long-acting monoclonal antibodies.

Combined Human–Animal Findings Reveal Synergistic Asthma Risk

Analyses of Danish registry data revealed an “additive” risk. Children hospitalized with RSV who had no parental history of asthma demonstrated a threefold increased risk of developing asthma (Hazard Ratio [HR] = 3.32; 95% Confidence Interval [CI] 3.21–3.43). This risk was substantially higher among children who experienced both severe RSV infection and maternal asthma (HR = 5.38; 95% CI 4.88–5.93).

Children with a father reporting a history of allergic rhinitis also demonstrated a significantly compounded risk, reinforcing that family history and infection act together to increase asthma susceptibility rather than acting independently.

Murine experiments provided mechanistic insight into these associations. Neonatal mice infected with PVM and born to allergic mothers developed severe asthma-like disease, including mucus hyperproduction and increased airway resistance. These effects were not observed in pups born to non-allergic mothers.

Further investigation showed that neonatal viral infection induced inflammatory dendritic cells to upregulate activating Fcγ receptors, including CD64, which facilitated enhanced uptake of allergen–IgG immune complexes transferred from the mother and subsequent antigen presentation to T cells.

Unexpectedly, instead of conferring protection, these maternal allergen-specific IgG antibodies promoted efficient antigen presentation and subsequent T-helper 2 (Th2) immune polarization, driving allergic airway inflammation.

When MPE8 antibodies were administered to allergic dams, thereby preventing viral infection in offspring, this cascade was disrupted. Pups receiving maternally derived antiviral protection did not develop airway eosinophilia, mucus overproduction, or airway hyperreactivity, effectively preventing asthma-like disease in this model despite later allergen exposure.

Implications for RSV Prevention and Childhood Asthma Risk

This study provides strong epidemiological and mechanistic evidence consistent with a causal role for early-life RSV infection in the development of childhood asthma, particularly in children with a family history of allergy or atopy.

The findings indicate that RSV infection is not merely a marker of asthma susceptibility but can act as a pathogenic amplifier of allergic risk by reshaping early immune development through Fc-receptor-mediated pathways.

Importantly, the results suggest that effective RSV immunoprophylaxis during early life may reduce the risk of asthma in susceptible populations. However, the authors emphasize that long-term human studies are needed to determine whether current maternal RSV vaccines or long-acting monoclonal antibodies, such as nirsevimab, can prevent asthma development beyond reductions in early wheezing illness.