# CD8 T cell and B cell collaboration following subunit vaccination

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $493,681

## Abstract

PROJECT SUMMARY
Some of the most successful vaccines to date, including those against the deadly viruses small pox, measles,
mumps, and rubella, comprise attenuated viral particles, capable of inducing both humoral and cellular
immunity. However, because protection through live infection is not feasible for many pathogens, including
HIV, malaria, tuberculosis, and cancer, alternative vaccine approaches are needed. A single immunization
with a protein subunit antigen and a combination of agonists toward pattern recognition receptors and CD40
(combined-adjuvant subunit vaccine) generates a magnitude of CD8+ and CD4+ T cell responses that is
exponentially larger than those typically induced by viral vectors in both mice and non-human primates. Given
the clinical promise of this vaccine platform, the careful study of the mechanisms controlling its potency may
uncover novel targets for the development of more effective prophylactic and therapeutic vaccines.
Over the past decade, studies of immunization and infection have revealed shared and distinct pathways
utilized in the generation of immunological memory. We have documented a unique metabolic program used
by expanding vaccine-elicited T cells, and requirements for cytokines (IL-15, IL-27) and transcription factors
(Tbet, Eomes) that are dispensable for the expansion of infection-elicited T cells. These discrepancies led us to
question other factors previously thought to be unimportant for the generation of CD8+ T cell responses, such
as the concurrent activation and proliferation of antigen-specific B cells. Given the disproportionate expansion
of B cells very early following subunit immunization, it seemed plausible that B cells could provide
costimulatory support for the ensuing CD8+ T cell response, either directly, or indirectly. Preliminary data
support this unconventional proposition. In fact, preliminary data also show that CD8+ T cell responses
likewise benefit the antibody response to subunit vaccination.
We do not yet understand the underlying mechanisms that integrate B cells and CD8+ T cells for the
generation of long-lived cellular and humoral immunity. Our proposal will use classic immunological
approaches to fully elucidate, specific to the context of subunit vaccination, 1) the role of B cell antigen
presentation and cytokine production in the regulation of CD8+ T cell survival and cell fate determination, 2) the
role of B cells in CD8+ T cell memory formation and maintenance, and 3) the mechanisms by which antigen-
specific CD8+ T cells influence B cell activation and antibody formation.

## Key facts

- **NIH application ID:** 10242218
- **Project number:** 5R01AI148919-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ross M Kedl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $493,681
- **Award type:** 5
- **Project period:** 2020-08-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242218

## Citation

> US National Institutes of Health, RePORTER application 10242218, CD8 T cell and B cell collaboration following subunit vaccination (5R01AI148919-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242218. Licensed CC0.

---

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