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Genomic signature of immune response against HIV-1 and its implications for dendritic cell-based therapeutic vaccine against HIV-1

Grant number: 13/06142-1
Support Opportunities:Regular Research Grants
Duration: October 01, 2013 - January 31, 2016
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Alessandra Pontillo
Grantee:Alessandra Pontillo
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Alberto José da Silva Duarte ; Laís Teodoro da Silva ; Luís Tiago Ferreira Romero Magalhães ; Sergio Crovella ; Telma Miyuki Oshiro Sumida

Abstract

Promising studies have been made in recent years around the world, addressing the epidemic of Acquired Immune Deficiency Syndrome (AIDS) and including a new line of treatment against HIV-1 by using autologous dendritic cells (DC) vaccination. In December 2004, the Brazilian phase I clinical trial of DC-based immune therapy against HIV-1 was published, reporting the data of 18 untreated HIV+ patients vaccinated with autologous DC pulsed with autologous inactivated HIV showed that half of the patients presented a good control of viral load. Currently, the Laboratory of Medical Investigation/LIM-56 (Faculty of Medicine, USP) is developing the second phase of this clinical trial with this vaccine and it will include new patients and will investigate several aspects of the treatment, aiming to answer some open questions about the use and the response to the vaccine. In particular one of great interest is to understand why some patients respond better than others to treatment, and what factors may influence the outcome of this therapy. Then, the goal of this project is to evaluate the immunegenetic profile of HIV-positive patients vaccinated with autologous DC primed with autologous HIV, by seeking attention on inflammation and innate immunity pathways, and to correlate with the response to immune therapy.So, we intend to determine the factors that may be related to both in vitro preparation of DC used for vaccination, and to the type of response of patients after HIV vaccine. Features of the genetic background (DNA analyses) of patients included in immune therapy, as well as gene expression (mRNA profile) during monocyte to DC differentiation, and circulating leukocytes before and after treatment will be evaluated by using updated "medium" and "high throughput" technologies to identify a genetic signature of response to vaccine. (AU)

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PONTILLO, ALESSANDRA; DA SILVA, RONALDO C.; MOURA, RONALD; CROVELLA, SERGIO. Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 10, n. 2, p. 512-518, . (13/06142-1)
MOURA, RONALD; PONTILLO, ALESSANDRA; D'ADAMO, PIO; PIRASTU, NICOLA; COELHO, ANTONIO CAMPOS; CROVELLA, SERGIO. Exome analysis of HIV patients submitted to dendritic cells therapeutic vaccine reveals an association of CNOT1 gene with response to the treatment. JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, v. 17, . (13/06142-1)
DA SILVA, WANESSA CARDOSO; OSHIRO, TELMA M.; DE SA, DANIEL COELHO; FRANCO, DILCILEA D. G. S.; NETO, CYRO FESTA; PONTILLO, ALESSANDRA. Data on inflammasome gene polymorphisms of patients with sporadic malignant melanoma in a Brazilian cohort. DATA IN BRIEF, v. 10, p. 33-37, . (13/06142-1, 12/18448-5, 12/09824-3)
DE LIMA, D. SOUZA; OGUSKU, M. M.; SADAHIRO, A.; PONTILLO, A.. Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis. INFECTION GENETICS AND EVOLUTION, v. 41, p. 240-244, . (13/06142-1)
SANTOS, MARINA L. S.; REIS, EDIONE CRISTINA; BRICHER, PAMELA N.; SOUSA, TAIS N.; BRITO, CRISTIANA F. A.; LACERDA, MARCUS V. G.; FONTES, COR J. F.; CARVALHO, LUZIA H.; PONTILLO, ALESSANDRA. yy Contribution of inflammasome genetics in Plasmodium vivax malaria. INFECTION GENETICS AND EVOLUTION, v. 40, p. 162-166, . (13/06142-1)
PONTILLO, A.; BRICHER, P.; LEAL, V. N. C.; LIMA, S.; SOUZA, P. R. E.; CROVELLA, S.. Role of Inflammasome Genetics in Susceptibility to HPV Infection and Cervical Cancer Development. Journal of Medical Virology, v. 88, n. 9, p. 1646-1651, . (13/06142-1)
REIS, EDIONE C.; DA SILVA, LAIS T.; DA SILVA, WANESSA C.; RIOS, ALEXANDRE; DUARTE, ALBERTO J.; OSHIRO, TELMA M.; CROVELLA, SERGIO; PONTILLO, ALESSANDRA. Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 14, n. 8, p. 1995-2002, . (17/22131-0, 15/23395-6, 13/06142-1)
REIS, EDIONE C.; LEAL, VINICIUS N. C.; DA SILVA, LAIS T.; DOS REIS, MARILIA M. L.; ARGANARAZ, ENRIQUE R.; OSHIRO, TELMA M.; PONTILLO, ALESSANDRA. Antagonistic role of IL-1 beta and NLRP3/IL-18 genetics in chronic HIV-1 infection. Clinical Immunology, v. 209, . (15/23395-6, 13/06142-1, 15/50650-7)
DE LIMA, DHEMERSON SOUZA; NUNES, VINICIUS C. L.; OGUSKU, MAURICIO M.; SADAHIRO, AYA; PONTILLO, ALESSANDRA; ALENCAR, BRUNA DE CUNHA. Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1 beta. INFECTION GENETICS AND EVOLUTION, v. 55, p. 313-317, . (15/23395-6, 13/06142-1, 14/23225-0)
DA SILVA, WANESSA CARDOSO; OSHIRO, TELMA MIYUKI; DE SA, DANIEL COELHO; FRANCO, DILCILEA D. G. S.; NETO, CYRO FESTA; PONTILLO, ALESSANDRA. Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression. CANCER GENETICS, v. 209, n. 10, p. 474-480, . (13/06142-1, 12/18448-5, 12/09824-3)
SANTOS, MARINA L. S.; REIS, EDIONE CRISTINA; BRICHER, PAMELA N.; SOUSA, TAIS N.; BRITO, CRISTIANA F. A.; LACERDA, MARCUS V. G.; FONTES, COR J. F.; CARVALHO, LUZIA H.; PONTILLO, ALESSANDRA. Contribution of inflammasome genetics in Plasmodium vivax malaria. INFECTION GENETICS AND EVOLUTION, v. 40, p. 5-pg., . (13/06142-1)

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