A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection

Abstract

Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo-dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-γ, IL-4, and IL-17, whereas only IL-12 and IFN-γ were induced by the higher-dose non-adjuvanted formulation. Lastly, passive transference of the higher-dose AH-adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing.

Zoonotic Epidemic of Sporotrichosis: Cat to Human Transmission

“…Studies to identify a vaccine candidate and the ideal adjuvant are ongoing [40,43]. Promising results using S .…”

“…Promising results using S . schenckii cell wall protein in an aluminum hydroxide (AH) adjuvanted formulation have been reported [43]. However, the use of AH as an adjuvant should be carefully reviewed for future studies in cats, since this compound is involved in feline vaccine-induced sarcomas [44].…”

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

“…In vitro assays with yeast cells opsonized with serum from immunized animals increased phagocytosis and inhibited the adhesion of the fungi to the fibroblasts [192]. …”

The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection

“…15 We also showed that the passive transference of sera from mice immunized with Al(OH) 3adjuvanted S. schenckii cell-wall proteins can induce protection in a subsequent challenge with the fungus. 16 The innate recognition of pathogens by pattern recognition receptors (PRRs) shapes the following adaptive immune response, so playing a critical role in determining the outcome of the infection. 17 To prevent pathogen invasion, PRRs survey the intracellular and extracellular space and play a critical role in the innate immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).…”

“…More recently, we showed that S. schenckii systemic mouse infection induces the development of a protective Th17 response, featuring both Th17 and Th17/Th1 cells and the augmented ex vivo release of interleukin‐17 (IL‐17) and IL‐22 . We also showed that the passive transference of sera from mice immunized with Al(OH) 3 ‐adjuvanted S. schenckii cell‐wall proteins can induce protection in a subsequent challenge with the fungus …”