A Sporothrix spp. enolase derived multi-epitope vaccine confers protective response in BALB/c mice challenged with Sporothrix brasiliensis. (May 2022)

• Record Type: Journal Article
• Authors: Portuondo, Deivys Leandro; Batista-Duharte, Alexander; Cardenas, Constanza; de Oliveira, Carlos S.; Borges, Júlio César; Téllez-Martínez, Damiana; Santana, Paula Andrea; Gauna, Adriana; Mercado, Luis; Mateus de Castilho, Bruna; Costa, Paulo; Guzmán, Fanny; Carlos, Iracilda Zeppone
• Is Part Of: Microbial pathogenesis. Volume 166(2022)
• Publication Date: 2022-05
• Subjects: Peptide vaccine -- Enolase -- Felis catus -- Sporothrix brasiliensis -- Sporotrichosis; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105539
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Sporotrichosis is a cosmopolitan mycosis caused by pathogenic species of Sporothrix genus, that in Brazil is often acquired by zoonotic transmission involved infected cats with S. brasiliensis . Previous studies showed that the Sporothrix spp. recombinant enolase (rSsEno), a multifunctional protein with immunogenic properties, could be a promising target for vaccination against sporotrichosis in cats. Nevertheless, the considerable sequence identity (62%) of SsEno with its feline counterpart is a great concern. Here, we report the identification in silico, chemical synthesis and biological validation of six peptides of SsEno with low sequence identity to its cat orthologue. All synthesized peptides exhibit B-cell epitopes on the molecular surface of SsEno and proved to be highly reactive with the serum of infected mice with S. brasiliensis and sera of cats with sporotrichosis. Interestingly, our study revealed that anti-peptide sera did not react with the recombinant enolase from Felis catus (cats, rFcEno), thus, may not trigger autoimmune response in these felines if used as a vaccine antigen. The immunization with peptide mixture (PeptMix) formulated with Freund adjuvant (FA), induced high levels of antigen-specific IgG, IgG1 and IgG2b antibodies that conferred protection upon passive transference in infected BALB/c mice with S. brasiliensis. We also observed, that the FA+PeptMix formulation induced a Th1/Th2/Th17 cytokine profile ex vivo, associated with protecting effect against the experimental sporotrichosis. Our results suggest that the six SsEno-derived peptides here evaluated, could be used as safe antigens for the development of vaccine strategies against feline sporotrichosis, whether prophylactic or therapeutic. Graphical abstract: Image 1 Highlights: PeptMix is a mixture of six peptides derived from Sporotrix spp enolase. PeptMix formulated with Freund's adjuvant proved to be immunogenic. FA+PeptMix induced high titers of specific IgG, IgG1 and IgG2b in mice. FA+PeptMix increased the ex vivo release of IL-12, IL-6, IFN-γ and IL-17 cytokines. FA+PeptMix induced protective antibodies against S. brasiliensis infection in mice.