RESUMEN
The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory B cells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than 1 year, and prominent tissue resident memory T (TRM) cell and B (BRM) cell populations were defined. Unexpectedly, germinal centre cells were identified consistently in many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRM cells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ TRM cells and CD8+ TRM cells were identified, with diverse additional virus-specific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.
Asunto(s)
Memoria Inmunológica , Células B de Memoria , Células T de Memoria , Mucosa Nasal , Nasofaringe , SARS-CoV-2 , Adulto , Humanos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/citología , COVID-19/inmunología , COVID-19/virología , Centro Germinal/inmunología , Centro Germinal/citología , Inmunoglobulina A/inmunología , Memoria Inmunológica/inmunología , Células B de Memoria/inmunología , Células T de Memoria/inmunología , Mucosa Nasal/inmunología , Mucosa Nasal/virología , Nasofaringe/virología , Nasofaringe/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/citología , SARS-CoV-2/inmunologíaRESUMEN
Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection has remained unclear. We evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating memory B cell responses to infection, and single mAb administration can continue to impact memory B cell responses to additional antigen exposures months later.