# Improving vaccination against type-2 T-independent antigens

> **NIH NIH R21** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2024 · $236,850

## Abstract

Summary
Infections with encapsulated bacteria are responsible for the death of millions of children and the elderly each
year. Capsular polysaccharides behave as T-independent antigens (TI) and vaccination based on these
carbohydrates provides protection against these infections. The efficacy of vaccines against TI antigens is
severely limited by their inability to induce recall responses upon revaccination or infection. This phenomenon
depends on inhibition of memory B cells by antigen-specific IgG generated in the primary response. The
mechanism behind this inhibitory activity however, remains unclear. The efficacy of vaccines critically
depends on adjuvants that can promote strong memory and influence Ig class switch recombination (CSR).
However, effective adjuvants for TI antigens vaccination are not available. The goal of our proposal is to
answer two outstanding questions regarding the response to TI antigens: what is the mechanism of the
inhibition of recall responses? and how can CSR and generation of memory B cells can be manipulated to
improve vaccination? For these studies we will use a mouse model of tularemia and will use Francisella
tularensis LPS, a model TI antigen that we showed activates B1 cells. In aim 1 we will test the hypothesis that
IgG-LPS immune complexes inhibit memory B1 cells reactivation and IgM production through complement
activation. We will test whether complement depletion or absence could restore the recall response to
vaccination with TI antigens and result in a more effective vaccine for tularemia. In aim 2 we will test the
hypothesis that novel adjuvants can improve recall responses to TI antigen by manipulating CSR in B1 cells
and/or improving generation of memory B1. Based on our preliminary results we will test a number of
potential adjuvant treatments with the goal of achieving sustained IgM and increased LPS-specific IgA
production but reduced IgG (responsible for inhibition of recall response). These adjuvants are also expected
to increased numbers of memory B1 cells. If successful, our studies will create proof of concepts that can
inform future development of more effective vaccination strategies for TI antigens.

## Key facts

- **NIH application ID:** 10808678
- **Project number:** 1R21AI176124-01A1
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** FABIO C RE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $236,850
- **Award type:** 1
- **Project period:** 2023-12-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808678

## Citation

> US National Institutes of Health, RePORTER application 10808678, Improving vaccination against type-2 T-independent antigens (1R21AI176124-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10808678. Licensed CC0.

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