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2050-01-01
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COMPARISON OF DNA VACCINES PRODUCING HIV-1 GAG AND LAMP/GAG CHIMERA IN RHESUS MACAQUES REVEALS ANTIGEN-SPECIFIC T-CELL RESPONSES WITH DISTINCT PHENOTYPES
Vacinas contra a AIDS / imunologia
Adjuvantes Imunológicos / genética
Adjuvantes Imunológicos / Farmacologia
Animais
CD28 Antígenos / análise
Linfócitos T CD4-Positivos / imunologia
Anticorpos HIV / sangue
HIV-1 / genética
HIV-1 / imunologia
Injeções Intramusculares
Interferon-gama / secreção
Antígenos comuns de leucócitos / análise
Glicoproteínas de Membrana Associadas a Lisossomos / genética
Glicoproteínas Associadas à Membrana Lisossômica / farmacologia
Macaca mulatta
Masculino
Subgrupos de linfócitos T / imunologia
Fator de Necrose Tumoral alfa / secreção
Vacinas , DNA / genética
Vacinas Sintéticas / imunologia
gag Produtos Gene, Vírus da Imunodeficiência Humana / genética
gag Produtos Gene, Vírus da Imunodeficiência Humana / imunologia
Author
Affilliation
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Southern Research Institute. Frederick, MD, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Pathogenesis Section. Maryland, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States / Johns Hopkins University School of Medicine. Department of Infectious Diseases. Baltimore, United States / Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Southern Research Institute. Frederick, MD, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Pathogenesis Section. Maryland, United States.
Vaccine Branch. Center for Cancer Research. National Cancer Institute at Frederick. Human Retrovirus Section. Frederick, MD, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States.
Johns Hopkins University School of Medicine. Department of Pharmacology. Baltimore, United States / Johns Hopkins University School of Medicine. Department of Infectious Diseases. Baltimore, United States / Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Abstract
Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4(+) T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4(+) responses with a phenotype of central memory-like T cells (CD28(+) CD45RA(-)), whereas the LAMP/Gag chimera induced CD4(+) responses with effector memory phenotype (CD28(-) CD45RA(-)). Antigen-specific T cells producing both IFN-gamma and TNFalpha were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.
DeCS
Vacinas contra a AIDS / genéticaVacinas contra a AIDS / imunologia
Adjuvantes Imunológicos / genética
Adjuvantes Imunológicos / Farmacologia
Animais
CD28 Antígenos / análise
Linfócitos T CD4-Positivos / imunologia
Anticorpos HIV / sangue
HIV-1 / genética
HIV-1 / imunologia
Injeções Intramusculares
Interferon-gama / secreção
Antígenos comuns de leucócitos / análise
Glicoproteínas de Membrana Associadas a Lisossomos / genética
Glicoproteínas Associadas à Membrana Lisossômica / farmacologia
Macaca mulatta
Masculino
Subgrupos de linfócitos T / imunologia
Fator de Necrose Tumoral alfa / secreção
Vacinas , DNA / genética
Vacinas Sintéticas / imunologia
gag Produtos Gene, Vírus da Imunodeficiência Humana / genética
gag Produtos Gene, Vírus da Imunodeficiência Humana / imunologia
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