# Deriving correlates of protection from influenza-specific antibody and T cell receptor analysis.

> **NIH NIH U19** · STANFORD UNIVERSITY · 2023 · $492,266

## Abstract

PROJECT SUMMARY
 Human adaptive responses to influenza vaccination and infection are complex, and can be impaired in a
variety of conditions, including pregnancy and advanced age, for reasons that are still unclear. We will carry out
extensive analyses of lymphocyte phenotypic repertoires, including those of NK cells, and the BCR and TCR
sequence repertoires expressed by influenza-specific B cells and T cells, in clinical cohorts designed to include
key vulnerable populations, pregnant women and the elderly, known to have impaired responses to influenza
vaccination or infection. To evaluate potential specific defects in stages of germinal center reactions, and the
proliferation and selection of influenza-specific lymphocytes that eventually become detectable in the blood, we
will carry out serial fine-needle aspirations (FNAs) from draining lymph nodes after vaccination, and in tonsils
from individuals receiving intranasal vaccine. Paired lymph node and blood data should enable detection of
defects in responses that have previously not been accessible to study in humans. We will use this approach to
identify key changes in immune responses with adjuvant (MF59) in influenza vaccination for the elderly, and
correlate these with resultant antibody quality.
 An additional goal of this Project will be to leverage prior extensive influenza-specific TCR and BCR
sequencing efforts in the Davis, Boyd and Robinson labs, as well as public data, to assemble databases of
confirmed influenza-specific receptor sequences to test specific hypotheses. With new computational
approaches, we will identify and validate convergent or public receptors that share sequence features indicating
that they bind similar epitopes. We will test whether the frequency, diversity, or particular epitope targets of such
receptor sequences can predict vaccine responses, and, more importantly, protection against live influenza viral
challenge. Two different influenza viral challenge cohorts will be used to validate our TCR and BCR predictors
of vaccine protection.
 This project will provide better understanding of age-related and pregnancy-related alterations in
influenza vaccine responses, as well as new knowledge about vaccine responses in secondary lymphoid tissues
including lymph nodes and tonsils. In the longer term, working within this U19, Project 2 will contribute to global
efforts to improve quantitative and predictive understanding of the human immune system. This knowledge
should help to shape strategies for improving and testing the next generation of influenza vaccines to prevent
future epidemics and pandemics. Many of these new approaches may also provide a template for developing
more effective vaccines in general.

## Key facts

- **NIH application ID:** 10656186
- **Project number:** 5U19AI057229-20
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Scott Dexter Boyd
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $492,266
- **Award type:** 5
- **Project period:** 2003-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656186

## Citation

> US National Institutes of Health, RePORTER application 10656186, Deriving correlates of protection from influenza-specific antibody and T cell receptor analysis. (5U19AI057229-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10656186. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*