Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Cryptococcus neoformans is a fungus classified by the World Health Organization as a critically important pathogen, posing a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semi-synthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) of C. neoformans. These semi-synthetic glycoconjugate vaccines contain the identical synthetic decasaccharide (M2 motif) antigen. This motif is present in serotype A strains, which constitute 95% of clinical cryptococcosis cases. This synthetic oligosaccharide was conjugated to two proteins (CRM197 and Anthrax 63 kDa PA) and tested for immunogenicity in mice. The conjugates elicited a specific antibody response that bound to the M2 motif but also exhibited additional cross-reactivity towards M1 and M4 GXM motifs. Both glycoconjugates produced antibodies that bound to GXM in ELISA assays and to live fungal cells. Mice immunized with the CRM197 glycoconjugate produced opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days, p = 0.06). While these findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. It could serve as a component in a multi-valent GXM motif vaccine, enhancing both strength and breadth of immune responses.
Article activity feed
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Maurizio Del Poeta
Review 3: "Semi-synthetic Glycoconjugate Vaccine Candidate Against Cryptococcus Neoformans"
Overall, while reviewers enjoyed the approach, they caution further optimization of the vaccine such as improving the glycan-protein conjugation is needed before an efficient vaccine candidate is achieved.
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Rajendra Upadhya
Review 2: "Semi-synthetic Glycoconjugate Vaccine Candidate Against Cryptococcus Neoformans"
Overall, while reviewers enjoyed the approach, they caution further optimization of the vaccine such as improving the glycan-protein conjugation is needed before an efficient vaccine candidate is achieved.
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Som G Nanjappa
Review 1: "Semi-synthetic Glycoconjugate Vaccine Candidate Against Cryptococcus Neoformans"
Overall, while reviewers enjoyed the approach, they caution further optimization of the vaccine such as improving the glycan-protein conjugation is needed before an efficient vaccine candidate is achieved.
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Strength of evidence
Reviewers: S G Nanjappa (University of Illinois Urbana-Champaign) | 📒📒📒 ◻️◻️
R Upadhya (Duke University) | 📘📘📘📘📘
M D Poeta (Stony Brook University) | 📘📘📘📘📘 -
