Development of an HK-fbp1-based vaccine platform against Cryptococcus neoformans
- 1Public Health Research Institute, and Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, 07103, United States
- 2Center for Immunity and Inflammation, and Department of Pediatrics, New Jersey Medical School, Rutgers University, Newark, NJ, 07103, United States
Abstract
Cryptococcal meningitis remains a leading cause of death among HIV/AIDS patients, and no antifungal vaccine is available in clinical use. We previously showed that mice immunized with a heat-killed preparation of Cryptococcus neoformans (Cn) fbp1{Delta} mutant (HK-fbp1) are protected against cryptococcosis and other invasive mycoses, suggesting that HK-fbp1 is an intriguing vaccine candidate for further study. Recent studies have reported that heat-killed wild type H99 (HK-H99) can also offer some protection in other vaccination models. Here we set out to decipher the differential protective capacity of HK-fbp1 versus HK-H99 across multiple conditions. We observed that HK-fbp1 confers superior protection in both prophylactic and therapeutic intranasal immunization settings than HK-H99, which was associated with greater activation of pulmonary CD4+ T cells and stronger airway IFN-{gamma} production. In addition, HK-fbp1 preparations were highly stable, retaining full protective efficacy even after 5 years of frozen storage. Mice intranasally immunized with two-dose HK-fbp1 were protected against challenge by up to 106 H99 cells, a 100-fold increase over the commonly used lethal inoculum. Addition of a CpG adjuvant ODN to HK-fbp1 (HK-bp1/ODN) led to a 5-fold reduction of the intranasal vaccine inoculum required for protection, and its single-dose intramuscular vaccination induced protection persisted for at least 3 months post vaccination. Together, these findings highlight the robust protective capacity and formulation versatility of HK-fbp1, supporting its further development as a stable, dose-sparing antifungal vaccine candidate.
Related
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- Therapeutic vulnerabilities of the drug-resistant fungal meningitis pathogen Cryptococcus neoformans
BibTeX
@misc{zhang2026development,
title = {{Development of an HK-fbp1-based vaccine platform against Cryptococcus neoformans}},
author = {Yu Zhang and Yina Wang and Keyi Wang and Lu Gan and Aaron Lemmer and Siddhi Pawar and Amariliz Rivera and Chaoyang Xue},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760669},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760669v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Development of an HK-fbp1-based vaccine platform against Cryptococcus neoformans
AU - Yu Zhang
AU - Yina Wang
AU - Keyi Wang
AU - Lu Gan
AU - Aaron Lemmer
AU - Siddhi Pawar
AU - Amariliz Rivera
AU - Chaoyang Xue
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760669
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760669v1
AB - Cryptococcal meningitis remains a leading cause of death among HIV/AIDS patients, and no antifungal vaccine is available in clinical use. We previously showed that mice immunized with a heat-killed preparation of Cryptococcus neoformans (Cn) fbp1{Delta} mutant (HK-fbp1) are protected against cryptococcosis and other invasive mycoses, suggesting that HK-fbp1 is an intriguing vaccine candidate for further study. Recent studies have reported that heat-killed wild type H99 (HK-H99) can also offer some protection in other vaccination models. Here we set out to decipher the differential protective capacity of HK-fbp1 versus HK-H99 across multiple conditions. We observed that HK-fbp1 confers superior protection in both prophylactic and therapeutic intranasal immunization settings than HK-H99, which was associated with greater activation of pulmonary CD4+ T cells and stronger airway IFN-{gamma} production. In addition, HK-fbp1 preparations were highly stable, retaining full protective efficacy even after 5 years of frozen storage. Mice intranasally immunized with two-dose HK-fbp1 were protected against challenge by up to 106 H99 cells, a 100-fold increase over the commonly used lethal inoculum. Addition of a CpG adjuvant ODN to HK-fbp1 (HK-bp1/ODN) led to a 5-fold reduction of the intranasal vaccine inoculum required for protection, and its single-dose intramuscular vaccination induced protection persisted for at least 3 months post vaccination. Together, these findings highlight the robust protective capacity and formulation versatility of HK-fbp1, supporting its further development as a stable, dose-sparing antifungal vaccine candidate.
SN - 2692-8205
ER -