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Experimental Human Pneumococcal Colonisation in Older Adults is Feasible and Safe, Not Immunogenic

Adler, H; German, EL; Mitsi, E; Nikolaou, E; Pojar, S; Hales, C; Robinson, R; ... Rylance, J; + view all (2020) Experimental Human Pneumococcal Colonisation in Older Adults is Feasible and Safe, Not Immunogenic. American Journal of Respiratory and Critical Care Medicine 10.1164/rccm.202004-1483OC. (In press). Green open access

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Abstract

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, and humoral immune responses were assessed by anti-capsular and anti-protein IgG levels.. 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: geometric mean titre (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.

Type: Article
Title: Experimental Human Pneumococcal Colonisation in Older Adults is Feasible and Safe, Not Immunogenic
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1164/rccm.202004-1483OC
Publisher version: https://doi.org/10.1164/rccm.202004-1483OC
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Human Challenge Model; Elderly & Aging; Antibody; Streptococcus pneumoniae; Colonisation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10110489
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