Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy

Autor(es)

Reis, Edione C. ^[1] ; da Silva, Lais T. ^[2] ; da Silva, Wanessa C. ^[2] ; Rios, Alexandre ^[1] ; Duarte, Alberto J. ^[2] ; Oshiro, Telma M. ^[2] ; Crovella, Sergio ^[3] ; Pontillo, Alessandra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, ICB, Dept Imunol, Lab Imunogenet, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Dermatol, Lab Invest Med LIM 56, Sao Paulo, SP - Brazil

^[3] Univ Fed Pernambuco, Dept Genet, Recife, PE - Brazil

• Tipo de documento: Artigo Científico
• Fonte: HUMAN VACCINES & IMMUNOTHERAPEUTICS; v. 14, n. 8, p. 1995-2002, 2018.
• Citações Web of Science: 2

Resumo

Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success. (AU)

• Processo FAPESP: 17/22131-0 - Avaliação do potencial de aplicação de células dendríticas aDC1 para imunoterapia anti-HIV
• Beneficiário: Telma Miyuki Oshiro Sumida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/23395-6 - Imunogenetica do inflamassoma, estudo translacional "da clinica a bancada,da bancada a clinica":analise das variações nos genes do inflamassoma em doenças autoinflamatorias monogênicas e multifatoriais para diagnostico diferencial e aplicações terapêutica
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/06142-1 - Perfil genômico da resposta imune ao HIV-1 e implicações para a vacina terapêutica com células dendríticas contra o HIV-1
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular