Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp

Autor(es)

Batista-Duharte, Alexander ; Tellez-Martinez, Damiana ; Portuondo, Deivys Leandro ; Carlos, Iracilda Zeppone

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 12, p. 9-pg., 2023-02-10.

Resumo

IntroductionRegulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. MethodsWe evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. ResultsTregs depletion enhanced the frequency of specific IFN gamma+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. DiscussionOur results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp. (AU)

• Processo FAPESP: 21/05494-8 - Modulação da resposta de células T reguladoras na terapia e prevenção da esporotricose. Uso de oligonucleotídeos antisentido como adjuvantes moleculares em vacina recombinante anti-Sporothrix
• Beneficiário: Iracilda Zeppone Carlos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/04250-0 - Papel das células t reguladoras CD4+CD25+FOXP3+ na resposta imune contra Sporothrix schenckii após infecção e vacinação
• Beneficiário: Alexander Batista Duharte
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado