# Development of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannans

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $777,874

## Abstract

PROJECT SUMMARY
Vaccines represent a highly effective public health measure to protect individuals from infectious diseases. Many
vaccines work by inducing antigen-specific antibodies that neutralize the pathogen or its products and promote
their clearance. Vaccines based on protein antigens usually require the addition of adjuvants to enhance
potency, breadth and duration of the antigen-specific adaptive immune response. Adjuvants promote vaccine
antigen immunogenicity by activating receptors of the innate immune system called pattern-recognition receptors
(PRRs) and/or modulating antigen pharmacokinetics. Aluminum salts are the most common adjuvants in FDA-
approved vaccines. Recently, vaccines including adjuvants that target specific PRRs, in particular toll-like
receptor (TLR)4 and TLR9, have also been approved by the FDA, paving the way for the development of
molecularly defined adjuvants. Investigating the potential of additional PRRs as adjuvant targets is of paramount
important to expand our vaccine toolbox and probe how different modalities of innate immune cell activation
impact the adaptive immune response. Here, we propose to use the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) Spike protein as a model antigen to test a new adjuvant formulation that contains
fungal ligands that target the PRR Dectin-2. Our preliminary results show that mannans (fungal cell wall
polysaccharides isolated from Candia albicans) alone or formulated with aluminum hydroxide enhance the
immunogenicity of pre-fusion stabilized, Spike trimers in mouse models of immunization. In particular, mannan
formulations, compared to aluminum hydroxide only, induce an early increase in anti-Spike antibody levels,
potentiate the induction of SARS-CoV-2 neutralizing antibodies, broaden the Spike epitopes that are targeted
and favor the switch towards immunoglobulin subclasses associated with higher effector functions and reduced
risk of vaccine-associated enhanced respiratory disease (VAERD). Here we hypothesize that mannans
formulated with alumOH induce a potent and durable adaptive immune response to SARS-CoV-2 Spike
by inducing specific innate immune pathways and activation programs. By combining detailed
immunogenicity and mechanistic analyses, our proposal will define a novel adjuvant formulation for
SARS-CoV-2 Spike and potentially other viral glycoproteins as well as shed new light on the biology of
Dectin-2.

## Key facts

- **NIH application ID:** 10338399
- **Project number:** 1R01AI165505-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Ivan Zanoni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,874
- **Award type:** 1
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338399

## Citation

> US National Institutes of Health, RePORTER application 10338399, Development of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannans (1R01AI165505-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10338399. Licensed CC0.

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