# Mannosidase-stabilized glycan immunogens for elicitation of high mannose patch antibodies

> **NIH NIH R21** · BRANDEIS UNIVERSITY · 2024 · $203,125

## Abstract

Project Summary/Abstract
HIV broadly neutralizing antibodies (bnAbs) most commonly target the High Mannose Patch (HMP), a
mannose-rich region of HIV Env in the vicinity of the V3 loop and the N332 glycan. HMP bnAbs (e.g.,
2G12, PGT128, BG18) tend to recognize non-reducing-terminal Man1α-2Man moieties within
oligomannose glycans; however, in immunizations with oligomannose glycoconjugates, antibodies are
rarely raised against Man1a-2Man, and instead bind to core motifs of the glycan. We hypothesize that in
vivo mannosidase trimming of Man1a-2Man termini is a major reason why antibodies do not develop
against this motif. In Aim 1, we will prepare stabilized oligomannose glycans, in which a sulfur linkage
prevents mannosidase cleavage of the Man1α-2Man, but structurally mimics the natural glycan and is
recognized by bnAbs. In Aim 2, we will immunize rabbits with CRM197 glycoconjugates containing the
stabilized or unstabilized glycans and compare the resulting antibodies’ HIV Env binding and
neutralization activity. We will also intensively characterize the ability of these antibodies to bind Man1a-
2Man using an oligomannose-focused glycan array.

## Key facts

- **NIH application ID:** 10816482
- **Project number:** 5R21AI174956-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Isaac Jonathan Krauss
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816482

## Citation

> US National Institutes of Health, RePORTER application 10816482, Mannosidase-stabilized glycan immunogens for elicitation of high mannose patch antibodies (5R21AI174956-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10816482. Licensed CC0.

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