# Strategies for generating high affinity antibodies against Gram negative bacteria

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $198,650

## Abstract

Project Summary
 Sugars cover the outer surfaces of bacteria and other pathogens and are usually very
effective at shielding these organisms from the immune system. Lacking T cell help, anti-glycan
responses are often of low affinity. Yet the structural complexity of oligosaccharides make them,
in principle, excellent candidates for species-specific markers should specific immune recognition
occur.
 The proposed research will use an approach for the generation of such immune responses
against unique tri- and tetrasaccharide motifs found on the outer surfaces of dominant pathogenic
strains of the Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia cepacia. The
method involves the chemical synthesis of the glycan motifs of interest in forms amenable to
bioconjugation, the attachment of those molecules to immunogenic virus-like particles with
precise control of the type and placement of the linkages used, and the use of a highly active
activator of natural killer T (NKT) cells as adjuvant, these cells being central to the elicitation of
robust immune responses against sugars in both natural infections and vaccines.
 This approach has been previously shown to generate ultra-high-affinity and protective
antibody responses in mouse against Gram-positive Streptococcus pneumoniae. Gram-negative
organisms remain a significantly tougher challenge; a potent immune response against pathogen-
specific cell-surface glycan motifs could represent an effective response. The studies proposed
here involve the creation and testing of eight candidate vaccine formulations against four
carbohydrate motifs, two for each species. Screening of primary immune response will allow for
optimization of the design and selection of final immunogens that will be carried into detailed
studies. High-affinity antibodies generated from these agents will be further explored to determine
their structures, binding affinities and kinetics, mutations from germ line, and abilities to protect
against pathogen challenge in a relevant mouse model.
 Success in this endeavor would identify great potential for the development of human
vaccines against these organisms and would provide confidence that the overall approach could
be useful for other glycan-based vaccines.

## Key facts

- **NIH application ID:** 9998494
- **Project number:** 1R21AI152528-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** M.G. Finn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,650
- **Award type:** 1
- **Project period:** 2020-03-02 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998494

## Citation

> US National Institutes of Health, RePORTER application 9998494, Strategies for generating high affinity antibodies against Gram negative bacteria (1R21AI152528-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9998494. Licensed CC0.

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