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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CTL and antibody responses to HIV-1 p17 and p24 antigens were monitored from 1986-1991, in 4 hemophiliacs. The patients had been infected with HIV-1 between 1980 and 1984. Two patients have remained asymptomatic while two progressed to AIDS in 1990. CTL were boosted by culturing with peptides from p17 aa 86-115, or p24 aa 265-279; and aa 270-373 or PHA. Lysis was measured on autologous or allogeneic targets pulsed with peptides or infected with recombinant vaccinia virus carrying HIV-1 gag or influenza A matrix genes. Antibodies to p17 and p24 were tested by ELISA using peptides and by Western blotting. High levels of CTL activity to p17 and p24 antigens could be generated only with lymphocytes from the two asymptomatic patients between 1986 and 1989, but these responses were absent in 1990 and 1991. Antibodies to p17 peptides disappeared in parallel with CTL activity. Antibodies to some p24 peptides also declined but most patients retained activity to others. In all patients a > or = 3-fold increase in CD8+ cell numbers occurred over time and accompanied the decline of CTL and antibody responses. The loss of CTL and p17 antibodies occurred irrespective of whether patients remained asymptomatic or progressed to AIDS in the intervening two years.
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PMID:Decline in CTL and antibody responses to HIV-1 p17 and p24 antigens in HIV-1-infected hemophiliacs irrespective of disease progression. A 5-year follow-up study. 128 55

The pathogenesis and clinical expression of HIV-1 infection in humans is considered in terms of classical pathogenetic studies of viral infections for which successful vaccines have been produced. The unique features of HIV pathogenesis are defined, and gaps in knowledge identified as a framework for considering designs for immune intervention. Envelope-derived candidate vaccines have been used in immunization and challenge experiments in SIV/macaque or HIV/chimpanzee models, presented either as vaccinia recombinant vectors or as subunits, singly or in sequence. These studies have been paralleled by clinical trials for safety and immunogenicity in seronegative individuals. Data generated will permit comparison of immune responses to specific antigens and delivery systems in animal models and in humans. In limited studies conducted under optimized conditions, non-human primates have been protected against virus challenge when immunized with some candidate vaccines or following passive transfer of high-titred antibody. Consideration of current information suggests that in order to prevent HIV infection it may be necessary to devise new strategies capable of inducing and maintaining high threshold titres of biologically relevant antibody as well as persistence of active cytotoxic T cells recognizing multiple epitopes.
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PMID:Development of a vaccine for the prevention of AIDS, a critical appraisal. 128 48

The transient expression of the HIV-1 gag genes and a HIV-1 ++trans-activator protein (tat)-encoded was made in cultured CV-1 cells. In recombinant plasmids, the gag gene was under the control of HIV-1 ++trans-activator sequence (tar) and the tat gene was under the control of a 7.5-kd vaccinia promoter. Transactivation of gag gene expression, which was stimulated by a tat gene expression product, was observed in the presence of wild vaccinia virus. The transaction was immunologically evaluated from the binding to monoclonal anti-p17 and anti-p24 antibodies. The findings lead to the discussion whether the regulatory proteins of HIV-1 can express in vaccinia virus vectors.
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PMID:[Expression of HIV-1 tat gene under the control of P 7,5 KD vaccinia virus promoter in CV-1 cells]. 128 22

Serum antibody responses were studied in detail in four vaccinia-naive volunteers in a phase I trial evaluating primary vaccination with a recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein (HIVAC-1e, Oncogen/Bristol-Myers Squibb), followed by booster immunization with baculovirus-derived rgp160 (VaxSyn, MicroGeneSys). Prior to boosting, low-titer Fc receptor (FcR)-mediated, antibody-dependent enhancing (ADE) activity was detected in two of four volunteers but no IgM, IgG, IgA, neutralizing activity, or complement-mediated ADE activity was detected. Two weeks after boosting, all four volunteers developed HIV-1-specific IgG with titers of 1:160 to 1:640 by immunofluorescence assay. IgG1 was present in sera from each individual, while IgG2 and IgG3 were present in sera from two individuals, and IgG4 was present in serum from one individual. IgM and IgA were undetectable in all sera. Only one volunteer had IgG to the heterologous HIV-1 isolates, RF, MN, and SF2, after boosting. Serum from this volunteer neutralized the vaccine strain, LAV/IIIB, but not the heterologous strains, RF, MN, and SF2. Antibodies from the remaining volunteers had no neutralizing activity. The neutralizing serum had a positive reaction in a peptide-based ELISA utilizing a peptide corresponding to the principal neutralizing domain of the third hypervariable region (i.e., V3 loop) of the envelope glycoprotein. Neutralizing activity was partially removed by adsorption to this peptide, suggesting that it contained a type-specific neutralizing vaccine epitope. A low titer (1:40 to 1:80) of complement-mediated ADE activity to HIV-1 IIIB was present in sera from three vaccinees after boosting. FcR-ADE activity for HIV-1 SF2 and SF-128A were present in sera from two of these three vaccinees. None of the volunteers developed antisyncytial antibodies. These results indicate that inoculation with recombinant vaccinia followed by rgp160 boosting is the most effective strategy to date for inducing serum antibodies to the envelope glycoproteins of HIV-1, but further study is needed to optimize the functionality and cross-reactivity of these responses.
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PMID:Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network. 128 35

Epstein-Barr virus (EBV) is a human viral pathogen of considerable importance. More than 95% of the human population world-wide becomes infected with the virus during childhood, although in the West infection may be delayed until adolescence. The infection only has an undesirable significant clinical outcome in a tiny minority of cases, but because the virus is so ubiquitous the minority is numerically very significant. The virus is associated with two important human cancers, endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma (NPC). These diseases have a very clearly defined geographical distribution in the Third World indicating a strong co-factor dependence. In the West, Epstein-Barr virus infection, when delayed to adolescence, is associated with infectious mononucleosis. The virus is also associated in the West with tumours arising in individuals undergoing immunosuppressive treatment or who are immunosuppressed as a result of HIV infection. More recently evidence has been obtained of an association with Hodgkin's disease which is very common in the West. A number of vaccines have been developed based on the EBV envelope glycoprotein gp340. Vaccination of those populations at risk from developing NPC or BL should lead to a reduction or elimination of these diseases. A safe and effective vaccine may also have a role in the prevention of EBV-related diseases in the West. Recombinant vaccinia, varicella and adenovirus vaccine vectors expressing gp340 are being developed and a recombinant-derived subunit vaccine based on the gp340 molecule is shortly to enter phase I human trials.
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PMID:Epstein-Barr virus vaccines. 132 99

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.
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PMID:Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network. 135 2

The CTL response to HIV-1 is more vigorous than for any known human pathogen and may be a significant factor in preventing the progression to symptomatic disease. T cell lines, generated by non-specific stimulation with PHA and IL-2, may be reproducibly used to identify HIV-1 isolate-invariant epitopes recognized by the CTL of infected individuals. The CTL response in each of 12 infected individuals to envelope and reverse transcriptase (RT) is dominated by the recognition of one or two viral isolate-invariant epitopes. Seven subjects respond to a single gp160 epitope; three subjects recognize 2 gp160 epitopes. There is a significant increase in recognition of epitopes in the C terminal 104 amino acids of gp41 (p less than 0.002); in fact 40% of the subjects that respond to gp160 recognize the C terminal 20-mer. The CTL-mediated lysis of gp160-expressing targets is MHC restricted, but not all individuals that share the same serologically defined class I-restricting element respond to the same epitope. Recognition of the terminal 20mer is restricted by both A30 and B8. The response to RT in six subjects is distributed over the RT protein. The six subjects recognize four separate regions defined by truncated RT-vaccinia recombinants, but none of the subjects' CTL demonstrate significant recognition of the RT epitope identified in H-2k mice and some humans.
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PMID:Cytotoxic T lymphocytes from HIV-1 seropositive individuals recognize immunodominant epitopes in Gp160 and reverse transcriptase. 137 97

Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia virus recombinants. Proliferative responses of spleen cells were comparable against env gp160, nef p27, and gag p25 recombinant proteins. No specific activity was observed against gag p18 protein. Env, nef, and gag-specific T-cell lines were generated by repeated stimulation of immune spleen cells with recombinant HIV-1 proteins. They were CD4 positive, proliferative, and also cytotoxic against HIV-transfected target cells. Specificity of the T-cell response against nef and gag protein was analyzed with synthetic peptides. Peptides nef 15, nef 16, and gag AM-30 were, respectively, reactive in nef- and gag-specific proliferative and cytolytic assays. The three peptides described have a relatively conserved amino acid sequence among HIV isolates and appear broadly immunoreactive among species.
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PMID:HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in nef p27 and gag p25 proteins. 137 36

The derivation of ethyl-methanesulfonate (EMS) mutagenized subclones from the CEM T-cell line has been described. These clones expressed CD4 and bound soluble gp120, however, two of the generated clones were markedly reduced in their ability to form syncytia after infection with either gp160-vaccinia vector or cell-free human immunodeficiency virus type 1 (HIV-1). Here, we asked at what stage(s) viral infection is blocked in these cells. Polymerase chain reaction (PCR) analysis revealed that at 6 and 72 h postinfection with HIV-1, cells of the syncytia-deficient clones expressed markedly reduced amounts of viral-specific DNA compared with cells of the parental line or the syncytia-positive clones. Long-term cultures revealed a marked delay in the appearance of reverse transcriptase (RT) activity in the supernatants of these subclones when compared with the parental line and viral replication did not lead to massive cell death. Syncytia formation in HIV-1-infected cultures of the syncytia-deficient subclones was enhanced by tumor necrosis factor alpha (TNF alpha) when added 24 h postinfection. In contrast, pretreatment with TNF alpha for 48 h followed by washing and infection of the cells with HIV-1 augmented syncytia formation of the syncytia-positive subclones, but not of the syncytia-negative subclones. Thus, the EMS-mutagenized subclones may provide a tool to study host cell factors required for the establishment of a productive HIV-1 infection and responsiveness to TNF alpha.
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PMID:Study of viral replication in HIV-1-infected CEM T-cell subclones which are reduced in their ability to form syncytia. 138 Feb 60

Previous studies have disagreed about the presence of O-linked carbohydrate epitopes on gp 120 of HIV, although antibodies against short-chain O-linked glycans neutralize HIV infection and block syncytium formation in vitro. To settle this question, we analysed the O-linked glycans of gp 120 by chemical methods using purified HIV-1 gp 120 from cells infected with recombinant vaccinia virus solely expressing gp 160 or gp 120. Alkaline borohydride degradation of recombinant gp 120 released monosaccharides and also slightly larger structures (di/trisaccharides) by a beta-elimination, confirming the presence of simple O-linked oligosaccharides. The functional activity as neutralisation epitopes of the O-linked oligosaccharides expressed on recombinant gp 120 was preserved, since fusion between uninfected CD4+ cells and cells infected with recombinant vaccinia was blocked by monoclonal antibodies to the O-linked oligosaccharides of gp 120. Although the mechanism for HIV induction of O-linked oligosaccharide neoantigens is unknown, these results indicate that the O-linked neutralization epitopes are inherent to the glycoprotein itself, and that the unusual appearance of simple O-linked oligosaccharides on gp 120 is independent of any interaction between the host cell and retroviral genes other than env.
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PMID:An O-linked carbohydrate neutralization epitope of HIV-1 gp 120 is expressed by HIV-1 env gene recombinant vaccinia virus. 138 7


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