Abstract
AbstractPneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy
Reference75 articles.
1. Huang, S. S. et al. Healthcare utilization and cost of pneumococcal disease in the United States. Vaccine 29, 3398–3412 (2011).
2. Daniels, C. C., Rogers, P. D. & Shelton, C. M. A review of pneumococcal vaccines: current polysaccharide vaccine recommendations and future protein antigens.J. Pediatr. Pharmacol. Ther. 21, 27–35 (2016).
3. Weller, S. et al. Human blood IgM ‘memory’ B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 104, 3647–3654 (2004).
4. Weller, S. et al. T-independent responses to polysaccharides in humans mobilize marginal zone B cells prediversified against gut bacterial antigens. Sci. Immunol. 8, eade1413 (2023).
5. Douglas, R. M., Paton, J. C., Duncan, S. J. & Hansman, D. J. Antibody response to pneumococcal vaccination in children younger than five years of age. J. Infect. Dis. 148, 131–137 (1983).