Serum immunoglobulin A (IgA) is a reliable biomarker of prior respiratory syncytial virus (RSV) infection in children under two years of age, a multinational study has confirmed.

Human RSV is a highly transmissible seasonal pathogen and the leading cause of lower respiratory tract infections in young children.

The study analysed data from 135 infants enrolled from a nested cohort in the LoewenKIDS birth cohort in Germany, led by teams at Martin Luther University Halle-Wittenberg and the Dutch National Institute for Public Health and the Environment, in collaboration with the PROMISE consortium.

Nasal swabs collected during acute respiratory infections were tested for RSV using reverse transcription polymerase chain reaction, while serum samples at ages one and two years were analysed for RSV-specific IgA and IgG antibodies against five viral proteins, as well as neutralising antibody titres.

An IgA threshold for serosurveillance

Concentrations of IgA antibodies targeting the RSV prefusion F protein (pre-F IgA) were significantly higher in infants who had RSV infections detected in the first year of life.

Using robust mixture discriminant analysis, researchers defined threshold values for pre-F IgA of 0.23 AU·mL⁻¹ at one year and 0.22 AU·mL⁻¹ at two years, indicating prior RSV infection. These values aligned closely with previously proposed seroresponse-based cut-offs.

The study also showed that IgA levels rose with age and reinfection. Importantly, IgA proved more specific than IgG in distinguishing infection-induced antibodies from maternally derived or passively transferred antibodies.

The researchers acknowledged that the study was limited by a small sample size and by participant attrition between years one and two, which may have reduced longitudinal reliability.

The exclusively German cohort may also limit generalisability, and some RSV infections could have been missed due to asymptomatic cases or incomplete sampling, they said. The lack of birth samples and maternal antibody data further constrains the interpretation of IgA kinetics.

A practical tool for RSV identification

Despite these constraints, the researchers noted that the validated IgA thresholds represent a practical tool for identifying RSV-naive infants, with potential applications in vaccine development and serosurveillance to help evaluate efficacy and inform immunisation strategies.

Further studies in larger, more diverse populations are advocated to confirm these findings and clarify IgA’s role in long-term immunity, they concluded.

Reference
Moureau A et al. Serum immunoglobulin A as a biomarker for respiratory syncytial virus infection in children aged <2 years. ERJ Open Res 2025;11(5):01288-2024.