Experimental human pneumococcal colonisation in older adults is feasible and safe, not immunogenic

Rationale Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives To establish experimental human pneumococcal colonisation in healthy adults aged 50—84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Methods Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Measurements and Main Results Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50—59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7μg/mL (1.9—3.8) pre-challenge versus 3.0 (1.9—4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8μg/mL (2.0—3.9) to 2.2μg/mL (1.6—3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7—10.1) led to recolonisation in 5/16 (31%). Conclusions In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.