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ACS Infect Dis ; 10(6): 2089-2100, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38819951

RESUMO

Cryptococcus neoformans is 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) of C. 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.


Assuntos
Anticorpos Antifúngicos , Criptococose , Cryptococcus neoformans , Vacinas Fúngicas , Glicoconjugados , Vacinas Conjugadas , Cryptococcus neoformans/imunologia , Animais , Vacinas Fúngicas/imunologia , Camundongos , Criptococose/prevenção & controle , Criptococose/imunologia , Glicoconjugados/imunologia , Glicoconjugados/química , Vacinas Conjugadas/imunologia , Anticorpos Antifúngicos/imunologia , Feminino , Polissacarídeos/imunologia , Polissacarídeos/química , Camundongos Endogâmicos BALB C , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/química , Antígenos de Fungos/imunologia
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