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

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Adler, Hugh, German, Esther L, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin, Hales, Caz, Robinson, Rachel, Connor, Victoria, Hill, Helen, Hyder-Wright, Angela D et al (show 19 more authors) , Lazarova, Lepa, Lowe, Catherine, Smith, Emma L, Wheeler, India, Zaidi, Seher R, Jochems, Simon P, Loukov, Dessi, Reiné, Jesús, Solórzano-Gonzalez, Carla, de Gorguette d'Argoeuves, Polly, Jones, Tessa, Goldblatt, David, Chen, Tao ORCID: 0000-0002-5489-6450, Aston, Stephen J ORCID: 0000-0002-0701-8364, French, Neil ORCID: 0000-0003-4814-8293, Collins, Andrea M, Gordon, Stephen B, Ferreira, Daniela M and Rylance, Jamie (2020) Experimental Human Pneumococcal Colonisation in Older Adults is Feasible and Safe, Not Immunogenic. American Journal of Respiratory and Critical Care Medicine, 203 (5). pp. 604-613.

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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.

Item Type:	Article
Uncontrolled Keywords:	Streptococcus pneumoniae, human challenge models, immunity, elderly, vaccination
Depositing User:	Symplectic Admin
Date Deposited:	14 Dec 2020 09:45
Last Modified:	18 Jan 2023 23:17
DOI:	10.1164/rccm.202004-1483oc
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3110245