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1.
AIDS Res Hum Retroviruses ; 23(11): 1442-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18184088

RESUMO

We report here the near full-length sequence characterization of 17 Danish clinical HIV-1 strains isolated from HLA-A02 patients not in need of ART, with relatively low viral loads and normal CD4 cell counts. Sequencing was performed directly on DNA extracted from short-term cocultures of PBMCs. The near full-length genomes did not contain any major insertions, deletions, or rearrangements. Sixteen of the isolates were characterized as nonrecombinant subtype B and one isolate as nonrecombinant subtype C. Phylogenetic analysis did not reveal any founder effect among the sequences. Also, we investigated the presence of infrequently targeted subdominant HLA-A02-binding CTL epitopes. The epitopes were conserved in the Danish strains as well as globally in reference sequences of all subtypes. Thus, the selected epitopes were not subtype-specific or region-specific. This lends support for the concept of a universal immunotherapeutic vaccine construct based on these epitopes.


Assuntos
Genoma Viral , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adulto , Idoso , Contagem de Linfócito CD4 , DNA Viral/genética , Dinamarca , HIV-1/isolamento & purificação , Antígenos HLA-A/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Homologia de Sequência , Carga Viral
2.
APMIS ; 119(8): 487-97, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21749448

RESUMO

For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure ≥10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.


Assuntos
Vacinas contra a AIDS/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas contra a AIDS/genética , Sequência de Bases , Dinamarca , Guiné-Bissau , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Masculino , Dados de Sequência Molecular , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência
3.
AIDS ; 23(11): 1329-40, 2009 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-19528789

RESUMO

OBJECTIVE: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). METHODS: Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 x 10 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed with seven CD8 T-cell epitopes and three CD4 T-cell epitopes. Epitope-specific responses were evaluated by intracellular cytokine staining for interferon-gamma, tumor necrosis factor alpha and interleukin-2 and/or pentamer labeling 3 weeks prior to, 10 weeks after and 32 weeks after the first immunization. RESULTS: Previously undetected T-cell responses specific for one or more epitopes were induced in all 12 individuals. Half of the participants had sustained CD4 T-cell responses 32 weeks after immunization. No severe adverse effects were observed. No overall or sustained change in viral load or CD4 T-cell counts was observed. CONCLUSION: These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could lead to stronger and more durable cellular responses to selected epitopes with the potential to control viral replication and prevent disease in HIV-1-infected individuals.


Assuntos
Vacinas contra a AIDS , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/uso terapêutico , Regulação Viral da Expressão Gênica , Infecções por HIV/prevenção & controle , HIV-1 , Adulto , Doença Crônica , Células Dendríticas/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral
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