Experimental Human Pneumococcal Colonization in Older Adults is Feasible and Safe, Not Immunogenic
| Autor: | David Goldblatt, Rachel Robinson, Esther L. German, Jesús Reiné, Angela D. Hyder-Wright, Seher Zaidi, Elena Mitsi, Jamie Rylance, Sherin Pojar, Lepa Lazarova, Stephen Aston, Stephen B. Gordon, Tessa Jones, Andrea M. Collins, Emma L. Smith, Polly De Gorguette D'Argoeuves, India Wheeler, Elissavet Nikolaou, Simon P. Jochems, Daniela M. Ferreira, Caz Hales, Tao Chen, Helen Hill, Hugh Adler, Catherine Lowe, Victoria Connor, Dessi Loukov, Neil French, Carla Solorzano-Gonzalez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Serotype Microbiological culture Critical Care and Intensive Care Medicine medicine.disease_cause Pneumococcal Vaccines Pathogenesis 0302 clinical medicine 030212 general & internal medicine Young adult Asymptomatic Infections Aged 80 and over biology Age Factors Middle Aged Antibodies Bacterial wt_100 Vaccination Streptococcus pneumoniae Carrier State Female Nasal Cavity Antibody Pulmonary and Respiratory Medicine wc_204 complex mixtures Pneumococcal Infections 03 medical and health sciences Immune system Immunity Culture Techniques Pneumococcal colonization medicine Humans Adverse effect Aged qw_4 business.industry Editorials Original Articles Models Theoretical Nasal Lavage Fluid Immunity Humoral Colonisation 030228 respiratory system Immunoglobulin G Immunology biology.protein Feasibility Studies business qw_142 |
| Zdroj: | Am J Respir Crit Care Med American Journal of Respiratory and Critical Care Medicine |
| ISSN: | 1073-449X |
| Popis: | RationalePneumococcal 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.ObjectivesTo 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.MethodsSixty-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 ResultsExperimental 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: GMT (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%).ConclusionsIn older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|