Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages

Autor(es)

dos Santos, Carina C. ; Walburg, Kimberley, V ; van Veen, Suzanne ; Wilson, Louis G. ; Trufen, Carlos E. M. ; Nascimento, Ivan P. ; Ottenhoff, Tom H. M. ; Leite, Luciana C. C. ; Haks, Marielle C.

• Tipo de documento: Artigo Científico
• Fonte: VACCINES; v. 10, n. 6, p. 14-pg., 2022-06-01.

Resumo

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-beta, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB. (AU)

• Processo FAPESP: 17/24832-6 - Desenvolvimento de vacinas baseadas em BCG recombinante: Tuberculose, Pertussis, Pneumococo e Schistosoma
• Beneficiário: Luciana Cezar de Cerqueira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/01271-0 - Identificação de biomarcadores de proteção e caracterização de um novo candidato vacinal contra tuberculose baseado em BCG recombinante
• Beneficiário: Carina Carvalho dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/03332-5 - Avanços no tratamento para TB: identificação de biomarcadores que predizem o resultado do tratamento e a caracterização molecular da resposta imune inata induzida pelo rBCG-LTAK63
• Beneficiário: Carina Carvalho dos Santos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto