# Immune response to pneumococcal vaccination in aging renal transplant recipients

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2020 · —

## Abstract

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The highest incidence of
disease occurs at the extremes of age. The elderly are at high risk of pneumococcal infection, have an increased
incidence of accompanying bacteremia and a higher mortality rate compared to younger adults. It is projected
that between 2000 and 2040, the number of Americans ≥65 years of age will more than double. The rapid
growth of the aging population has resulted in a significant increase in elderly individuals with end-stage renal
disease (ESRD). Moreover, older (>65 yrs) individuals are the fastest growing population requiring renal
replacement therapy. Streptococcus pneumoniae is the most common bacterial pathogen and the incidence of
invasive pneumococcal disease (IPD) is 12x higher in renal transplant (RT) and dialysis recipients. It is
recommended that both elderly>65 and RT/dialysis recipients be vaccinated with a combination of the 13-
valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine.
Previous studies have demonstrated suboptimal vaccine responses in both RT and dialysis populations and
failed to elucidate the possible foundation of the disappointing immune responses to the PCV regimens. Our
preliminary studies suggest that IgM memory B cells and expression of tumor necrosis family receptors TACI
and BAFF-R, both crucial in the immune response to polysaccharide antigens, are deficient in the RT
recipients. We hypothesize that poor responses to pneumococcal vaccines in aging dialysis and RT populations
are in part related to an altered inflammatory environment and in part related to B cell perturbations,
specifically in memory B cell numbers and in TNFR expression. We will test this hypothesis by first measuring
antibody responses and B cell numbers and phenotype to pneumococcal vaccination in RT and dialysis
recipients >65 years of age and compare these groups to healthy age-matched and young persons. In addition,
we hypothesize that elderly RT/dialysis recipients have a unique combination of inflammatory markers and
intrinsic B cell defects, or profile, and that this profile dictates vaccine responses. To this purpose, Investigate
the underlying mechanisms of altered B cell responses in the aging RT and dialysis populations by elucidating
inflammatory environment, B cell functionality and B cell surface receptor and gene expression using single
cell quantitative PCR, specifically focused on the TNF superfamily. Finally, we will study the effect of PCV/PPV
vaccination on markers predicting graft rejection to ensure vaccine safety. We postulate that CpG-ODN may be
a useful adjuvant to restore full expression of TACI, however in the RT population this may be an inappropriate
adjuvant. We will therefore define the effects of CpG-ODN and BAFF on expression of TNFR and tolerance
associated genes.
This work is important and novel because it examines antigen-specific responses post-immuniza...

## Key facts

- **NIH application ID:** 9813949
- **Project number:** 5I01CX001658-02
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** M.A. Julia WESTERINK
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9813949

## Citation

> US National Institutes of Health, RePORTER application 9813949, Immune response to pneumococcal vaccination in aging renal transplant recipients (5I01CX001658-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9813949. Licensed CC0.

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