# Conjugate vaccines for prevention and treatment of cryptococcosis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $742,433

## Abstract

Cryptococcosis is an invasive mycotic disease caused by the fungus Cryptococcus neoformans. In the second
half of the 20th century, cryptococcosis increased dramatically in medical importance because of its association
with HIV infection, organ transplantation and immunosuppression caused by medical advances. Therapy with
antifungal drugs remains unsatisfactory, particularly in non-HIV cases, as the infection tends to be chronic,
difficult to eradicate and recur after therapy. There are no vaccines available for the prevention of
cryptococcosis, or for any other mycoses. Host defense against C. neoformans infection involves both humoral
and cellular mechanisms. C. neoformans is unusual in that it is the only encapsulated human pathogen and the
polysaccharide capsule is an absolute requirement for virulence. The major capsular polysaccharide is
glucuronoxylomannan (GXM). Antibodies to the capsular polysaccharide are protective providing a strong
rationale for the development of vaccines that target this antigen. This proposal seeks funds to develop a novel
conjugate vaccine based on synthetic and natural oligosaccharides, which will focus the resulting immune
response into making only protective antibodies. Conjugate vaccines have been remarkably successful in
reducing the incidence of several bacterial encapsulated pathogens and the same should be possible for
cryptococcosis. We plan to take advantage of all that we have learned about antibody-mediated immunity
against C. neoformans to develop a novel conjugate vaccine against a major human fungal pathogen. In
addition, two new developments provide a new approach to this problem: 1) advances in synthetic organic
chemistry have led to the generation of chemically defined oligosaccharides representing GXM motifs; and 2)
the discovery that C. neoformans makes large amounts of oligosaccharides in culture that are raw materials for
vaccine construction. The availability of new materials in the form of natural and synthetic oligosaccharides for
the polysaccharide component of the conjugate vaccine bring the promise of making highly immunogenic
compounds that focus the immune response to elicit only protective antibodies. Three aims are proposed: 1. To
establish the epitopes in C. neoformans GXM recognized by protective and non-protective antibodies; 2. To
generate a set of novel protein-polysaccharide conjugate vaccines based on natural and synthetic
oligosaccharides of expressing C. neoformans GXM structural motifs; 3. To establish the immunogenicity and
efficacy novel conjugate vaccines against experimental C. neoformans infection.

## Key facts

- **NIH application ID:** 9944833
- **Project number:** 1R01AI152078-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Arturo Casadevall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $742,433
- **Award type:** 1
- **Project period:** 2020-03-02 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944833

## Citation

> US National Institutes of Health, RePORTER application 9944833, Conjugate vaccines for prevention and treatment of cryptococcosis (1R01AI152078-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9944833. Licensed CC0.

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