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

Adler, Hugh ORCID: https://orcid.org/0000-0003-4437-2298, German, Esther, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Hales, Caz, Robinson, Rachel, Connor, Victoria, Hill, Helen, Hyder-Wright, Angela, Lazarova, Lepa, Lowe, Catherine, Smith, Emma, Wheeler, India, Zaidi, Seher, Jochems, Simon ORCID: https://orcid.org/0000-0002-4835-1032, Loukov, Dessi, Reiné, Jesús, SolorzanoGonzalez, Carla, de Gorguette d’Argoeuves, Polly, Jones, Tessa, Goldblatt, David, Chen, Tao ORCID: https://orcid.org/0000-0002-5489-6450, Aston, Stephen J, French, Neil, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 and Rylance, Jamie ORCID: https://orcid.org/0000-0002-2323-3611 (2021) 'Experimental Human Pneumococcal Colonization in Older Adults is Feasible and Safe, Not Immunogenic'. American Journal of Respiratory and Critical Care Medicine, Vol 203, Issue 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
Subjects:	QW Microbiology and Immunology > Bacteria > QW 142 Gram-positive bacteria (General) QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole. WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 204 Pneumococcal pneumonia. Staphylococcal pneumonia WT Geriatrics. Chronic Disease > Geriatrics > WT 100 General works
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1164/rccm.202004-1483OC
Depositing User:	Rachael O'Donoghue
Date Deposited:	13 Nov 2020 13:05
Last Modified:	17 Aug 2022 08:59
URI:	https://archive.lstmed.ac.uk/id/eprint/16060

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