Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential

Autor(es)

Kischkel, Brenda ^[1] ; Boniche-Alfaro, Camila ^[1] ; Menezes, Isabela de Godoy ^[2] ; Rossi, Suelen Andreia ^{[1, 3]} ; Angeli, Claudia Blanes ^[4] ; de Almeida, Sandro Rogerio ^[2] ; Palmisano, Giuseppe ^[4] ; Lopes-Bezerra, Leila ^[1] ; Nosanchuk, Joshua D. ^{[5, 6]} ; Taborda, Carlos Pelleschi ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Trop Med Inst, Dept Dermatol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Biomed Sci Inst, Dept Parasitol, Sao Paulo - Brazil

^[5] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY - USA

^[6] Albert Einstein Coll Med, Dept Med, Div Infect Dis, New York, NY - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 12, NOV 22 2021.
• Citações Web of Science: 0

Resumo

As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map Histoplasma capsulatum epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (M phi). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and M phi, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-gamma, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species. (AU)

• Processo FAPESP: 18/18257-1 - EMU concedido no processo 14/06863-3: sistema de cromatografia líquida configurado para análise de carboidratos, aminoácidos, peptídeos e glicoproteínas
• Beneficiário: Giuseppe Palmisano
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 16/08730-6 - Patogenicidade fúngica: efeito do tabagismo, resposta imune e a modulação vacinal na paracoccidioidomicose e na histoplasmose
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/06863-3 - Modificações pós-traducionais para o diagnóstico de câncer e doenças parasitárias: abordagens metodológicas e implicações biológicas
• Beneficiário: Giuseppe Palmisano
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/25780-0 - Apresentação por células dendríticas humanas de peptídeos com capacidade vacinal e prospecção de antígenos pan-fúngicos na paracoccidioidomicose
• Beneficiário: Suélen Andreia Rossi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/26402-1 - Prospecção de novos epítopos com potencial vacinal no controle da infecção experimental por Histoplasma capsulatum
• Beneficiário: Brenda Kischkel
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/15549-1 - Modificações pós-traducionais nos processos biológicos e no diagnóstico da Doença de Chagas: novas abordagens metodológicas e implicações biológicas
• Beneficiário: Giuseppe Palmisano
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2