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Reviews of "Semi-synthetic Glycoconjugate Vaccine Candidate Against Cryptococcus Neoformans"

Reviewers: S G Nanjappa (University of Illinois Urbana-Champaign) | 📒📒📒 ◻️◻️ • R Upadhya (Duke University) | 📘📘📘📘📘 • M D Poeta (Stony Brook University) | 📘📘📘📘📘

Published onMar 25, 2024
Reviews of "Semi-synthetic Glycoconjugate Vaccine Candidate Against Cryptococcus Neoformans"
key-enterThis Pub is a Review of
Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans
Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans

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.

To read the original manuscript, click the link above.

Summary of Reviews: Reviewers find the preprint's characterization of GMX monomers in a glycoconjugate vaccine to be a useful step forward for the development of fungal vaccines. However, they do find the evidence for immunogenicity to be less conclusive from the mice studies compared to the in vitro results. 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.

Reviewer 1 (Som G N…) | 📒📒📒 ◻️◻️

Reviewer 2 (Rajendra U…) | 📘📘📘📘📘

Reviewer 3 (Maurizio Del P…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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