Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty healthy HIV negative volunteers were randomised to receive 200 micrograms of rgp120W61D in either: 3D-MPL and QS21, with an oil and water emulsion (SBAS-2) (13); or 3D-MPL and QS21 (SBAS-1) (11); or alum (six). Immunizations were given at 0, 4 and 28 weeks and 23 (77%) participants completed the schedule. Adverse events were more frequent (P < 0.001) and more severe (P < 0.001) in the SBAS-2 group. Binding antibodies to the homologous rgp120W61D were detected after the first immunisation only in those receiving SBAS-1 and SBAS-2, were maximal after the third immunization in all three groups, and persisted to week 84 only in the novel adjuvant groups. These differences were significant (p = 0.02). Neutralising antibodies to TCLA-strains of HIV-1 were observed after the second immunization in all three groups, were maximal after the third immunization, but did not neutralise homologous or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120W61D were maximal after the second immunization and reached very high values in the SBAS-2 group. HIV-1 specific CD8+ MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint. SBAS-2 with rgp120W61D induced antibody titres as high as those seen in HIV infection, but the quality of the antibodies remained different in that there was no evidence of primary isolate neutralisation. Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8+ cytotoxicity was not demonstrated.
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PMID:A phase I trial in HIV negative healthy volunteers evaluating the effect of potent adjuvants on immunogenicity of a recombinant gp120W61D derived from dual tropic R5X4 HIV-1ACH320. 1064 17

Phase I and II studies have been carried out with several candidate HIV-1 vaccines in seronegative volunteers. Vaccines consisting of rgp 120 stimulated moderate levels of neutralizing antibodies against homologous, TCLA adapted viruses, but did not induce CD8+ CTL responses. Canarypox vectors stimulate CD8+ CTL responses, but little neutralizing activity. The latter can be increased in titer by boosting recipients of canarypox vectors with rgp120 vaccines. Large-scale placebo-controlled efficacy trials are underway with two rgp120 vaccines: AIDSVAX B/B (VaxGen, Inc.) in the United States, and AIDSVAX B/E in Thailand. The canarypox-rgp120 combined regimen has been proposed for study in an intermediate-sized, "test-of-concept" efficacy trial by the NIAID-sponsored HVTN, with an experimental design intended to provide information on the potential in vitro correlates of immunity. The results from these studies, and the methodology used in their conduct, should facilitate the refinement of conventional and novel approaches to the development of safe and effective HIV vaccines.
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PMID:HIV vaccines for prevention of infection and disease in humans. 1114 38

The relative resistance of human immunodeficiency virus type 1 (HIV-1) primary isolates (PIs) to neutralization by a wide range of antibodies remains a theoretical and practical barrier to the development of an effective HIV vaccine. One model to account for the differential neutralization sensitivity between Pls and laboratory (or T-cell line-adapted [TCLA]) strains of HIV suggests that the envelope protein (Env) complex is made more accessible to antibody binding as a consequence of adaptation to growth in established cell lines. Here, we revisit this question using genetically related PI and TCLA viruses and molecularly cloned env genes. By using complementary techniques of flow cytometry and virion binding assays, we show that monoclonal antibodies targeting the V3 loop, CD4-binding site, CD4-induced determinant of gp120, or the ectodomain of gp41 bind equally well to PI and TCLA Env complexes, despite large differences in neutralization outcome. The data suggest that the differential neutralization sensitivity of PI and TCLA viruses may derive not from differences in the initial antibody binding event but rather from differences in the subsequent functioning of the PI and TCLA Envs during virus entry. An understanding of these as yet undefined differences may enhance our ability to generate broadly neutralizing HIV vaccine immunogens.
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PMID:Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. 1122 97

Linear conserved B cell epitopes in envelope glycoprotein of long-term nonprogressors (LTNPs) HIV-1 CRF01_AE were determined. The envelope sequences of HIV-1 subtype E from Thailand were aligned to define consensus sequences. Then the peptides corresponding to these predicted regions were synthesized as peptides represent C1, C2, C3, C5, V2, V3, and gp41 regions. After that, the neutralizing B cell epitopes were determined by neutralized competitive assay with pool sera of typical progressor and LTNP HIV-1 CRF01_AE patients against HIV-1 CRF01_AE 24 primary isolates (PI) and laboratory strains (TCLA). We found that the strength and breadth of neutralization were greater for sera from LTNPs compared with sera from typical progressors. Peptides C1E and C2E could inhibit primary isolates but not the TCLA strain in LTNP sera. The new B cell epitopes, which were located in the C1 and C2 regions of CRF01_AE against primary HIV-1 isolates, were identified in HIV-1 CRF01_AE LTNPs. This may be important in HIV-1 vaccine development and trial.
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PMID:Conserved neutralizing epitopes of HIV type 1 CRF01_AE against primary isolates in long-term nonprogressors. 1518 28