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1.
J Acquir Immune Defic Syndr ; 42(2): 135-9, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16760794

RESUMO

An effective HIV type 1 (HIV-1) vaccine will likely require elicitation of broadly reactive cell-mediated immune (CMI) responses against divergent HIV-1 clades. We compared anti-HIV-1 T-cell immune responses among 363 unvaccinated adults infected with diverse HIV-1 clades. Response rates to clade B Gag and/or clade B Nef in Botswana (95%) and Cameroon (98%) were similar when compared with those in countries previously studied, including Brazil (92%), Thailand (96%), South Africa (96%), Malawi (100%), and the United States (100%). Substantial cross-clade cell-mediated immune responses in Botswana and Cameroon confirm previous findings in a larger, more genetically diverse collection of HIV-1 samples.


Assuntos
Antígenos HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T , Linfócitos T/imunologia , Adolescente , Adulto , Botsuana , Camarões , Células Cultivadas , Feminino , Produtos do Gene gag/imunologia , Produtos do Gene nef/imunologia , Humanos , Interferon gama/biossíntese , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Produtos do Gene nef do Vírus da Imunodeficiência Humana
2.
J Infect Dis ; 191(9): 1427-34, 2005 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15809900

RESUMO

BACKGROUND: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. METHODS: Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. RESULTS: Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.


Assuntos
Soropositividade para HIV/imunologia , HIV-1/imunologia , Imunidade Celular , Linfócitos T/imunologia , Adulto , Sequência Consenso , Reações Cruzadas , Feminino , Produtos do Gene nef/química , Produtos do Gene nef/genética , Geografia , HIV-1/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Produtos do Gene nef do Vírus da Imunodeficiência Humana
3.
J Immunol ; 168(2): 562-8, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11777947

RESUMO

Virus-specific CD4(+) T cell responses have been shown to play a critical role in controlling HIV-1 replication. Candidate HIV-1 vaccines should therefore elicit potent CD4(+) as well as CD8(+) T cell responses. In this report we investigate the ability of plasmid GM-CSF to augment CD4(+) T cell responses elicited by an HIV-1 gp120 DNA vaccine in mice. Coadministration of a plasmid expressing GM-CSF with the gp120 DNA vaccine led to only a marginal increase in gp120-specific splenocyte CD4(+) T cell responses. However, immunization with a bicistronic plasmid that coexpressed gp120 and GM-CSF under control of a single promoter led to a dramatic augmentation of vaccine-elicited CD4(+) T cell responses, as measured by both cellular proliferation and ELISPOT assays. This augmentation of CD4(+) T cell responses was selective, since vaccine-elicited Ab and CD8(+) T cell responses were not significantly changed by the addition of GM-CSF. A 100-fold lower dose of the gp120/GM-CSF bicistronic DNA vaccine was required to elicit detectable gp120-specific splenocyte proliferative responses compared with the monocistronic gp120 DNA vaccine. Consistent with these findings, i.m. injection of the gp120/GM-CSF bicistronic DNA vaccine evoked a more extensive cellular infiltrate at the site of inoculation than the monocistronic gp120 DNA vaccine. These results demonstrate that bicistronic DNA vaccines containing GM-CSF elicit remarkably potent CD4(+) T cell responses and suggest that optimal Th cell priming requires the precise temporal and spatial codelivery of Ag and GM-CSF.


Assuntos
Vacinas contra a AIDS/genética , Linfócitos T CD4-Positivos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Ativação Linfocitária , Vacinas de DNA/genética , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/genética , Animais , Linfócitos T CD4-Positivos/metabolismo , Movimento Celular/genética , Movimento Celular/imunologia , Regulação Viral da Expressão Gênica/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Injeções Intramusculares , Interferon gama/biossíntese , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos BALB C , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Plasmídeos/administração & dosagem , Plasmídeos/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia
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