# Conjugate vaccines for prevention and treatment of cryptococcosis - COVID-19 Revision Supplement

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $268,837

## Abstract

Project Summary Supplement
The original grant seeks to develop a novel conjugate vaccine based on synthetic and natural oligosaccharides
for Cryptococcus neoformans. This supplement changes the scope to a human clinical trial with the overall
goal to investigate novel applications of human convalescent plasma in the prevention and therapy of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19). This
is necessary before a vaccine is realized for COVID-19. Thus, the central hypothesis of this project is that
COVID-19 convalescent plasma can be successfully used as a treatment strategy to mitigate the spread and
mortality of the ongoing COVID-19 pandemic. This randomized open label trial will assess the efficacy and
safety of Anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms as
well as in high risk exposures as prevention of infection. Serological assays specific for SARS-CoV-2 will be
used to assess the amount of antibodies that are present in the blood of plasma donors and recipients.
Project Summary (from Parent Grant): …FIRST 4 sentences truncated…. 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-
protec...

## Key facts

- **NIH application ID:** 10265635
- **Project number:** 3R01AI152078-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Arturo Casadevall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $268,837
- **Award type:** 3
- **Project period:** 2020-06-17 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265635

## Citation

> US National Institutes of Health, RePORTER application 10265635, Conjugate vaccines for prevention and treatment of cryptococcosis - COVID-19 Revision Supplement (3R01AI152078-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10265635. Licensed CC0.

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