Nasal mucosal IgA targeting the respiratory syncytial virus pre-fusion F protein predicts protection against RSV infection more accurately than serum antibodies, according to a study published in Nature Communications.
Researchers tracked 342 participants across 52 households in a peri-urban area of The Gambia over 12 months. The team conducted weekly respiratory PCR surveillance alongside longitudinal serum and nasal sampling at enrollment, six months, and 12 months to evaluate systemic and mucosal humoral immunity to RSV-A and RSV-B antigens.
Predicting infection risk
Using a Bayesian hierarchical framework, the investigators evaluated the predictive performance of different antibody biomarkers against RSV infection. Mucosal IgA to the RSV-A pre-fusion F (PreF) protein proved to be the single strongest predictor of protection against infection, recording an area under the receiver operating characteristic curve of 0.72. By comparison, serum IgG against PreF achieved an AUC of 0.66.
Combining both serum IgG and mucosal IgA against PreF into a dual biomarker model improved predictive accuracy to an AUC of 0.73. Analysis of participant antibody levels showed that serum and mucosal responses operate largely independently, with correlation coefficients between serum IgG and mucosal IgA to the same protein ranging from 0.02 to 0.28.
Transmission and age dynamics
Surveillance identified 81 PCR-confirmed RSV infections across 76 individuals, with 17.3 percent displaying symptoms during the week before or after testing positive. Incorporating serological boosting data to account for an estimated 80 percent PCR detection rate identified 18 additional infections, resulting in an overall attack rate of 27 percent. Attack rates varied by age, reaching 53 percent in children under five years old and falling to 11 percent in adults aged 46 years and older.
Age also influenced antibody kinetics and protection thresholds. Children under five years old had lower baseline titres prior to infection but exhibited the largest relative post-infection boosts, rising 12.5-fold for serum IgG and 14.9-fold for mucosal IgA. To achieve 50 percent protection against infection, children under five required mucosal PreF IgA titres of 247,708 AU/mL, compared to 5,722 AU/mL in participants aged 16 years and older.
