# DC-subset-tailored vaccines

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $390,000

## Abstract

PROJECT SUMMARY
There is a fundamental gap in our understanding of why only certain vaccines promote formation of long-lasting
and protective antibody responses. Dendritic cells (DC) are professional antigen presenting cells that regulate
adaptive immune responses; thus, we think that understanding the role DCs in regulating B cell responses will
be key to the development of universal vaccines targeting influenza and HIV. Our experimental data suggest
that the major limitations of the relatively ineffective vaccines currently in use or in development might be that:
1) they do not specifically target Langerhans cells (LCs) and 2) the antigen dose is not tailored to maximize the
activation of the LCs. Our long-term goal is to understand the role of different DC populations in humoral immune
responses and to use that knowledge to design DC-subset-tailored vaccines, with a special focus on influenza
and HIV. In pursuit of that goal, the objectives of this application are to: 1) define the mechanisms by which
steady state LCs promote germinal center (GC)-dependent humoral immune responses; 2) to characterize the
regulatory loop by which high antigen dose and CD103+ DCs inhibit GC-dependent responses induced by LCs;
and 3) to test the feasibility of the DC-subset-tailored influenza vaccine. Our central hypothesis is that LCs drive
functionally distinct Tfh cells in an antigen dose-dependent manner that ultimately determines whether humoral
immune responses are mounted or not. The rationale for the proposed research is that, once the details of how
LCs initiate humoral immune responses and regulate each other are known, the process can likely be
manipulated to yield innovative approaches for prevention and treatment of a variety of diseases. Guided by
strong preliminary data, our hypothesis will be tested in these three Specific Aims: 1. Define the mechanism by
which LCs promote GC-dependent humoral immune responses; 2) Determine the mechanism by which high
antigen dose and CD103+ DCs inhibit LC-induced GC-dependent humoral immune responses; and 3) Determine
the effect of antigen dose on development of protective anti-viral responses. For Aim 1, a well characterized
targeting approach will be combined with LC-specific knock out transgenic mouse models, bone marrow
chimeras, imaging, in vitro cell cultures and flow cytometry to define the molecular requirements of LC-induced
humoral immune responses. In Aim 2, in vitro co-culture experiments and in vivo adoptive cell transfer systems
will be used to characterize how high antigen dose and CD103+ DCs regulate LC-induced immune responses.
In Aim 3, we will immunize mice through LCs with different doses of flu-HA and then challenge with live influenza
to determine the feasibility of the antigen-tailored influenza vaccine. The proposed hypothesis and experimental
models are highly novel and innovative. This project is significant because it will advance and expand our
understanding on how humoral immune respo...

## Key facts

- **NIH application ID:** 10197028
- **Project number:** 5R01AI146420-02
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Botond Z Igyarto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2020-06-17 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197028

## Citation

> US National Institutes of Health, RePORTER application 10197028, DC-subset-tailored vaccines (5R01AI146420-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197028. Licensed CC0.

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