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1. Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+) T cell responses in HIV-1-infected individuals.

Author

Núria Climent, Susana Guerra, Felipe García, Cristina Rovira, Laia Miralles, Carmen Elena Gómez, Núria Piqué, Cristina Gil, José María Gatell, Mariano Esteban, and Teresa Gallart

Subjects
Medicine, Science
Abstract

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+) T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+) T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+) T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Published
2011
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2. Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+) T cell responses in HIV-1-infected individuals

Author

Mariano Esteban, Laia Miralles, Teresa Gallart, José M. Gatell, Felipe García, Cristina Gil, Susana Guerra, Cristina Rovira, Carmen E. Gómez, Núria Piqué, Núria Climent, Universitat de Barcelona, and UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología

Subjects
CD4-Positive T-Lymphocytes, Chemokine, HIV Antigens, viruses, lcsh:Medicine, Apoptosis, HIV Infections, Antigen Processing and Recognition, CD8-Positive T-Lymphocytes, Monocytes, Cytotoxic T cell, Immunologia, lcsh:Science, AIDS Vaccines, Multidisciplinary, biology, Vaccination, Flow Cytometry, Innate Immunity, Cèl·lules T, Cytokines, Medicine, Infectious diseases, Chemokines, Research Article, HIV infections, Virus ADN, Medicina, Immune Cells, Genetic Vectors, Antigen presentation, Immunology, Retrovirology and HIV immunopathogenesis, T cells, Antigen-Presenting Cells, Viral diseases, Genes, env, Microbiology, complex mixtures, Virus, Antigen, Vacunes antivíriques, Virology, Vaccine Development, Humans, Biology, Viral vaccines, Poxviridae, CCL19, lcsh:R, Immunity, HIV, Viral Vaccines, Dendritic Cells, HIV-1, biology.protein, Clinical Immunology, Infeccions per VIH, lcsh:Q, DNA viruses, CD8
Abstract

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B, This work was supported by grants from the Spanish Ministry of Health (FIS 2006-1259, RIS-Spanish Cooperative Network on AIDS Research, FIS 2009-80145 and FIS 2009-11078), the Spanish Ministry of Education and Science (BIO2004-03954, SAF2005-05566, SAF2008-02036 and SAF2008-04395), the Spanish Foundation for AIDS Research (FIPSE 36344/02, 36536/05, 36551/06 and 36750/08), Fundación Botín, the EU (EuroVac QLRT-PL-1999-01321 and QLK2-CT-2002-01867), MuNanoVac-EU-STREP-037200. FIPSE is a non-profit Foundation including: Spanish Ministry of Health, Abbott Laboratories, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme and Roche

Published
2011

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