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

Abstract

Running head: Experimental pneumococcal colonisation and aging Despite low rates of pneumococcal colonisation detected in older people in previous community surveys, experimental colonisation was established in 39% of volunteers aged ≥ 50 years. The serological and functional immune responses of older adults to challenge and colonisation with live pneumococci were markedly different to those of young adults. Experimental human pneumococcal colonisation was safe, supporting the use of this methodology in clinical trials of pneumococcal vaccines for older people.

Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae

“…However, metaanalyses have suggested that PPV23 may only be beneficial against IPD, with no effect against the far more common nonbacteremic pneumonia (Moberley et al, 2013;Latifi-Navid et al, 2018). Along with its disputed efficacy against pneumonia, PPV23 has no protective effect against pneumococcal colonization (Adler et al, 2020).…”

“…Why older people are so vulnerable to disease caused by S. pneumoniae is likely to be multifactorial including comorbidities, relative immunodeficiency, malnutrition and defective swallowing (Janssens and Krause, 2004;Zalacain, 2004;Arndt, 2015). Disease follows pneumococcal carriage and reported nasopharyngeal and oropharyngeal carriage rates in older people vary between 0-39% (Krone et al, 2015;Adler et al, 2020;Almeida et al, 2020;Smith et al, 2020;Yasuda et al, 2020). Unlike adults aged 18-64yrs, older adults do not appear to benefit from the natural immune effects of pneumococcal colonization events that are thought to protect against recolonization and disease (Ferreira et al, 2013;Adler et al, 2020).…”

“…Disease follows pneumococcal carriage and reported nasopharyngeal and oropharyngeal carriage rates in older people vary between 0-39% (Krone et al, 2015;Adler et al, 2020;Almeida et al, 2020;Smith et al, 2020;Yasuda et al, 2020). Unlike adults aged 18-64yrs, older adults do not appear to benefit from the natural immune effects of pneumococcal colonization events that are thought to protect against recolonization and disease (Ferreira et al, 2013;Adler et al, 2020). Older people often display a disorganised inflammatory state, which is associated with an increased mortality risk and has been termed 'Inflammageing' (Franceschi and Campisi, 2014;Ferrucci and Fabbri, 2018).…”

Serum levels of anti-PspA and anti-PspC IgG decrease with age and do not correlate with susceptibility to experimental human pneumococcal colonization

“…Samples from volunteers aged 50 years and more are from the "Experimental human pneumococcal carriage model (Programme Grant Research): working towards a nasal vaccine for pneumonia. The effect of age on immune function" study performed between June 2016 and October 2018 (REC reference 16/NW/0031, Protocol number 15-053, IRAS project ID 196461) [25]. Healthy adults aged 50-84 years were approached using advertisements, research volunteer databases and primary care patient lists.…”

Human challenge trials in vaccine development

“…Similarly, a challenge model using 10 5 CFUs of Bordetella pertussis has been established which results in asymptomatic colonization of the upper respiratory tract and provides insights into the lifecycle and transmission of B. pertussis [ 52 ]. Advancements have also been made in understanding pneumococcal colonization in adults aged over 50 years by the expansion of the experimental human pneumococcal colonization model in this age group [ 53 ].…”