Infection with pandemic H1N1 influenza or porcine respiratory coronavirus drives localised and individualised antibody repertoires, whereas immunisation promotes repertoire convergence in pigs

Abstract Introduction Respiratory viruses elicit mucosal and systemic immunity, yet how tissue compartmentalisation and exposure route shape B cell repertoires remain unclear. Methods Using the pig model, we characterised antibody repertoires in bronchoalveolar lavage, tracheobronchial lymph nodes, spleen, and blood following intranasal infection with pandemic influenza virus (pH1N1) or porcine respiratory coronavirus (PRCV), and after intramuscular PRCV immunisation. Results Infection induced highly compartmentalised responses, with antigen-associated clones enriched in lung, lymph nodes and spleen but with limited presentation in blood. These clones were largely private, indicating individualised responses, and displayed tissue-specific diversity. The similar tissue distributions between pH1N1 and PRCV infections suggest a conserved spatial organisation, although differential lymph node involvement indicates pathogen-specific effects. In contrast, intramuscular immunisation generated more convergent, public repertoires in blood, characterised by reduced clonal size diversity. Conclusion Together, these findings show that despite stable germline usage, functional antibody responses are shaped by the route of antigen exposure, clonal selection, and host specific factors, resulting in distinct repertoire architectures between infection and immunisation.