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

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, 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 and older. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7ug/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 2.8ug/mL (2.0-3.9) to 2.2ug/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.

The epidemiologic and biologic basis for classifying older age as a high-risk, immunocompromising condition for pneumococcal vaccine policy

“…However, recent studies appear to have resolved this seeming paradox, specifically by finding carriage prevalence of older adults approaching that in children when using molecular techniques and testing reservoirs other than the nasopharynx, such as the oropharynx and saliva [53,91,92]. Studies of experimental pneumococcal colonization indicate that colonization can be established in healthy older adults, but it failed to confer serotype-specific immunity [82]. The authors hypothesized that reduced colonization or altered postcolonization immunity in older adults may partially explain their increased susceptibility to pneumococcal infection.…”

“…A major component of naturally acquired immunity to IPD is antibodies to pneumococcal proteins rather than anticapsular antibodies [102,108]. There is an age-related decline in naïve B cells, which show decreased affinity maturation and isotype switching [83,86] and accumulation of senescent antigen-experienced memory B cells (MBCs) [82,83]. With age, MBCs also lose their capacity for differentiation into plasma cells and this is likely to contribute to higher incidence of pneumococcal disease in older adults [83,109].…”

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

“…However, meta-analyses have suggested that PPV23 may only be beneficial against IPD, with no effect against the far more common non-bacteremic 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 co-morbidities, 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 re-colonization 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 re-colonization 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 ).…”