Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans.
Semi-synthetic glycoconjugate vaccine candidate against Cryptococcus neoformans.
复制标题
针对新型隐球菌的半合成复合糖疫苗候选物。
DOI：
10.1101/2024.02.02.578725
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Casadevall,Arturo
中科院分区：
文献类型：
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作者：
Crawford,ConorJ;Liporagi-Lopes,Livia;Coelho,Carolina;Santos,SamuelR;Nicola,AndréMoraes;Wear,MaggieP;Vij,Raghav;Oscarson,Stefan;Casadevall,Arturo
Cryptococcus neoformansis a fungus classified by the World Health Organization as a critically important pathogen, which poses a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semisynthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) ofC. neoformans. These semisynthetic glycoconjugate vaccines contain an identical synthetic decasaccharide (M2 motif) antigen. This antigen is present in serotype A strains, which constitute 95% of the 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 toward 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 weakly opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days,p= 0.06). These findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. This antigen could serve as a component in a multivalent GXM motif vaccine.
