Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

Abstract

Microsporum canis is the most common dermatophyte in pets and is of zoonotic importance but currently there is no effective vaccine available to prevent dermatophytosis. The aim of this work was to assess the immunogenicity and protective efficacy of secreted components (SC) from M. canis adjuvanted with the monophosphoryl lipid-A (MPLA), in a vaccine study using the guinea pig as an experimental model. Animals were vaccinated with either the SC adjuvanted with the MPLA, the MPLA adjuvant alone or PBS three times at two-week intervals, until 42 days prior to M. canis infection. A blind evaluation of dermatophytosis symptoms development and fungal persistence in skin was monitored weekly. The antibody response towards the SC and the levels of Interferon (IFN)γ and Interleukin-4 expressed in peripheral blood mononuclear cells were assessed along or at the end of the study period respectively. The animals that received MPLA had a significantly lower clinical score than those inoculated with PBS. However, no significant difference was observed between the guinea pigs vaccinated with the SC adjuvanted with the MPLA and those having received MPLA alone. The results also showed that vaccination induced a strong antibody response towards the SC and an increase in IFNγ mRNA level. Our results show that the MPLA adjuvant used in this vaccine study can induce per se a partial protection against a M. canis infection. Although they induce a delayed-type hypersensitivity reaction in guinea pigs, the SC do not confer a protection under the present experimental conditions.

Robust In Vitro and In Vivo Neutralization against Multiple High-Risk HPV Types Induced by a Thermostable Thioredoxin-L2 Vaccine

“…Conceivably, immunoglobulin germ-line configurations may be more adapted to recognize, and be activated by, PfTrx-L2. Further, the TLR-4 agonist monophosphoryl lipid A may be more effective in guinea pigs than in mice (29). Also, although both Balb/c mice and guinea pigs express TLR-4 receptors on dendritic cells, signaling might be more sustained in the latter species.…”

“…Taking into account the above scaffold improvement, the availability of different neutralization assays and the need for a L1-VLP comparison, we present here the results of a comprehensive immunization study evaluating the relative performance of monovalent P. furiosus thioredoxin-HPV16 L2 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) 3 (PfTrx-16L2), a mixture of thioredoxin-L2 antigens derived from HPV16, 31, 51 (PfTrx-L2 mix), and HPV16-L1-VLPs. The PfTrx-L2 antigens were administered at moderate doses and formulated in the human-compatible adjuvant aluminum hydroxide-monophosphoryl lipid A (MPLA).…”

Towards a Standardized Procedure for the Production of Infective Spores to Study the Pathogenesis of Dermatophytosis

“…For other strains, there was no or little differences between media, especially between PDA and SAB, which also efficiently allowed dermatophyte growth and sporulation (e.g., T. rubrum IHEM 13894 and T. interdigitale IHEM 00584). Furthermore, the growth of Microsporum species, and particularly M. canis IHEM 21239, was slightly increased on YEN, in favour of the previous use of this medium to produce fungal suspensions of M. canis for infection in in vitro [25] and in vivo [26,27] models. However, in order to standardize the medium used for all species and strains, the PDA appears more appropriate.…”

“…Experimental infection models described in the literature use different compositions of inoculum, consisting in suspensions enriched in unicellular infective spores, namely microconidia [17][18][19][20][21][22][23] or arthroconidia [24][25][26][27][28][29], or in a mix of microconidia and hyphae [30][31][32][33][34][35]. Microconidia, as well as macroconidia, are a type of thallic spores resulting from lateral or terminal budding of hyphae.…”

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

“…[159], B. dermatitidis [160], Cryptococcus spp. [161], Coccidioides spp., Histoplasma capsulatum [162], Microsporum canis [163], Paracoccidioides spp. [164], Pneumocystis jirovecii [165], Sporothrix spp.…”