# Effects of aging on primary and secondary vaccine responses in a 15-year longitudinal cohort

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $704,782

## Abstract

Summary
 Age-related defects in human immune function have been most studied in the context of influenza
vaccination and infection, or other settings where an individual's history of prior antigenic exposures and
adaptive immune memory complicates analysis. In contrast, both young and elderly individuals are also able to
form new primary immune responses following novel antigen exposures. Vaccine-mediated protection of
communities against emergent infectious diseases such as Ebola and Zika viruses will rely on new primary
adaptive immune responses across age categories.
 We will comprehensively analyze the adaptive immune responses in young adult and elderly subjects to
three different kinds of primary vaccinations administered by parenteral or oral routes: the Hepatitis A (HAV)
inactivated and aluminum salt-adjuvanted viral vaccine, and two vaccines for Typhoid (injected polysaccharide
or oral attenuated bacterial vaccine). Importantly, we will study these primary immune responses in a unique
clinical cohort: the longitudinal Stanford-Ellison cohort of young adult (20-35 years) and elderly (60-95 years)
subjects whose yearly influenza vaccine responses have been studied extensively for the past nine years, and
will continue to be studied during the grant period so that explicit comparison of primary and secondary
responses can be made in the same individuals. We will use novel single B cell and T cell antigen receptor
repertoire analysis and transcriptional phenotyping methods, and single cell monoclonal antibody expression
and characterization, to define the B cell and T cell clones that respond to each primary vaccination. In a
subset of subjects, we will also obtain bone marrow aspirates to analyze the bone marrow plasma cell
populations, and identify which clones from the acute vaccine responses in the blood contribute to the bone
marrow plasma cell pool versus the memory B cell pool. In addition, gut microbiota data will be collected to
evaluate for potential interactions between vaccines and microbiota.
 The impact of this Project will stem from a combination of opportunities for comprehensive study of primary
and secondary adaptive immune responses and the effects of aging on human immune systems: 1) a uniquely
well-characterized longitudinal cohort of young and elderly subjects in whom clinically-relevant primary vaccine
responses can be studied in parallel with secondary responses to influenza vaccination, 2) single-cell
characterization of vaccine-specific B cell and T cell receptor repertoires and phenotypes in combination with a
panel of standard immunological assays, 3) tracking of vaccine-stimulated B cell clones from the acute vaccine
response in the blood, to residence in the bone marrow plasma cell pool, and 4) integration with microbiome
data and other significant clinical data.

## Key facts

- **NIH application ID:** 10129883
- **Project number:** 5R01AI130398-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Scott Dexter Boyd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $704,782
- **Award type:** 5
- **Project period:** 2017-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129883

## Citation

> US National Institutes of Health, RePORTER application 10129883, Effects of aging on primary and secondary vaccine responses in a 15-year longitudinal cohort (5R01AI130398-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129883. Licensed CC0.

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