# Methods to synthesize oligosaccharide-fusion protein conjugates and enhancement of their antigenicity

> **NIH NIH R01** · UNIVERSITY OF TOLEDO · 2020 · $550,227

## Abstract

Project Summary
Carbohydrates have been used in some of the world most effective glycoconjugate
vaccines. However, traditional glycoconjuates produced by oligosaccharide isolation
have failed to produce effective vaccines against the ESKAPE pathogen Pseudomonas
aeruginosa. ESKAPE pathogens are pathogens that have acquired extensive
antimicrobial resistance (AMR) and are becoming increasingly difficult and in some
cases impossible to treat. There is an urgent need to identity new approaches for
controlling AMR which is projected to cause up to 10 million deaths annually and cost
100 trillion dollars in cumulative economic damage by the year 2050. This application
addresses AMR by using a powerful soluble polymer-based synthetic method to
chemically synthesize serotype-independent oligosaccharide epitopes from the
lipopolysaccharide (LPS) of P. aeruginosa bacteria. In addition, we develop robust
methods to site-specifically conjugate these synthetic oligosaccharide domains with
protective fusion protein domains prepared by synthetic biology-based methods. We
develop methods to further site-specifically conjugate these glycoconjugates with lipid
adjuvants to form well-defined single molecule lipoglycoproteins. These materials will be
used to determine the beneficial role of both the oligosaccharide and the protein in
provoking a protective immune response. In addition, the work will allow mapping of the
protective oligosaccharide and protein epitopes. The antigens are designed to overcome
known obstacles to development of a protective immune response against this
bacterium and to provide protection against multiple bacterial strains. A second aspect of
the proposal is the systematic study of the resulting conjugates in mice that will lead to
new approaches to enhance vaccine immunogenicity in humans. The approach takes
advantage of naturally occurring antibodies in humans that can participate in enhancing
the recognition of the vaccine by the immune system. This proposal takes advantage of
a collaboration between investigators trained in organic chemistry, immunology, and
molecular mechanisms of pathogenesis.

## Key facts

- **NIH application ID:** 9859535
- **Project number:** 1R01AI148570-01
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Steven Sucheck
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $550,227
- **Award type:** 1
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859535

## Citation

> US National Institutes of Health, RePORTER application 9859535, Methods to synthesize oligosaccharide-fusion protein conjugates and enhancement of their antigenicity (1R01AI148570-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859535. Licensed CC0.

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