Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults.
Document Type
Article
Publication Date
2-1-2024
Original Citation
Ravichandran S,
Erra-Diaz F,
Karakaslar E,
Marches R,
Kenyon-Pesce L,
Rossi R,
Chaussabel D,
Nehar-Belaid D,
LaFon D,
Pascual V,
Palucka K,
Paust S,
Nahm M,
Kuchel G,
Banchereau J,
Ucar D.
Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. Nat Immunol. 2024;25(2):316-29.
Keywords
JGM, Male, Humans, Female, Aged, Vaccines, Conjugate, Antibodies, Bacterial, Double-Blind Method, Streptococcus pneumoniae, Vaccination, Pneumococcal Vaccines, Polysaccharides
JAX Source
Nat Immunol. 2024;25(2):316-29.
ISSN
1529-2916
PMID
38182669
DOI
https://doi.org/10.1038/s41590-023-01717-5
Grant
We thank T. Helenius for aid in scientific writing, M. Collet for help with dbGAP data upload, research staff in the UConn Center on Aging for their help in recruitment and sample collection and D. Luo and P. Gabriel from the JAX Genomic Technologies and Single Cell cores for help with generating the sequencing data. The JAX single-cell service is supported, in part, by the JAX Cancer Center P30 CA034196 (to K.P., D.U., J.B., D.C. and S.P.). We thank members of the Ucar lab for critical feedback during the progress of the study. This study was made possible by generous financial support from NIH grants under award numbers R01AG052608 (to J.B.), U01AI165452 (to D.U. and G.A.K.), P30AG067988 Older Americans Independence Pepper Center (to G.A.K.) and R01AI142086 (to D.U. and J.B.) and JAX Cancer Center Brooks Scholarship (to S.R.). Opinions, interpretations, conclusions and recommendations are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Abstract
Pneumococcal 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.