Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Sabin type 1 vaccine strain of poliovirus is probably the safest and most successful live-attenuated vaccine virus used in humans. Its widespread use since the early 1960s has contributed significantly to the virtual eradication of poliomyelitis in developed countries. We have reported previously the construction of an intertypic antigen chimaera of poliovirus, based on the Sabin 1 strain, and proposed that this virus could be modified to express on its surface antigenic determinants from other pathogens. We describe here the construction and characterization of a poliovirus antigen chimaera containing an epitope from the transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1). In antibody absorption experiments, the virus chimaera inhibited neutralization of HIV-1 by antipeptide monoclonal antibodies specific for the gp41 epitope and significantly reduced the group specific neutralizing activity of HIV-1-positive human sera. Rabbit antisera raised by subcutaneous injection of the polio/HIV chimaera in adjuvant was shown to be specific for HIV-1 gp41 in peptide-binding assays and by western blotting. Moreover, the antisera neutralized a wide range of American and African HIV-1 isolates and also inhibited virus-induced cell fusion. Monoclonal antibodies against the HIV-1 derived regions of the chimaera also neutralized HIV-1. These results establish the potential of using poliovirus for the presentation of foreign antigens and suggest that Sabin 1 poliovirus/HIV chimaeras could offer an approach to the development of an HIV vaccine.
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PMID:An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. 254 97

Conformational analysis, based on ECEPP (Empirical Conformational Energy Program for Peptides) using the chain build-up procedure, was applied to determine the low-energy conformations for a series of tetrapeptides. The tetrapeptides are components of larger peptides which have been found to bind to the CD4 receptor of monocytes. Several previous studies have implicated the tetrapeptide units investigated here as being critical to the biological activities of the full peptides. Five such tetrapeptides were studied: Ser-Ser-Asn-Tyr (from ribonuclease A), Thr-Thr-Asn-Tyr (from peptide T, known to block human immunodeficiency virus from attaching to CD4+ T cells), Thr-Ile-Asn-Tyr (from polio virus coat protein, which is less active than the other peptides in binding to CD4 receptors), Ser-Ser-Ala-Tyr (from the gp 120 coat protein of human immunodeficiency virus, a variant of the peptide T sequence, active in blocking viral attachment to CD4+ cells), and the tetrapeptide from an active synthetic pentapeptide, Asn-Thr-Lys-Tyr (from Asn-Thr-Lys-Tyr-Thr). Using a 7 kcal/mol cutoff, the low-energy conformations for each peptide were computed. Approximately 20,000 conformations were computed for each tetrapeptide. Residue probability profiles were determined for each tetrapeptide. All tetrapeptides except for the polio sequence showed flexibility in the sense that many low-energy conformations were possible. In previous studies, it was postulated that the critical tetrapeptide units would adopt conformations similar to the one observed in a segment of ribonuclease A, residues 22-25, a beta-bend, which is part of an octapeptide segment (residues 19-26) that is homologous to the sequence of peptide T.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of beta-bend conformations of tetrapeptides with their activities in CD4-receptor binding assays. 259 73

In the last decade it appeared more than once that blood donations were contaminated by hitherto unknown viruses. Due to this fact, further steps have to be included into the manufacturing procedure of even up to now safe products from human plasma to eliminate potential new risks. A procedure is described which enables the pasteurization of antithrombin III analogous to albumin without major changes in the properties of the molecule. Thus the new product Kybernin HS/P was obtained. The efficacy of the pasteurization step was tested using relevant human pathogenic viruses. The following titers of important viruses could be totally inactivated within the pasteurization time (h) given in brackets HIV: (human immunodeficiency virus) greater than or equal to 10(6.7) (1), CMV (cytomegaly virus) greater than or equal to 10(4.5) (1), HSV (Herpes simplex virus) greater than or equal to 10(6.8) (4), Polio (poliomyelitis virus) greater than or equal to 10(6.9) (4).
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PMID:[Properties and virus safety of a pasteurized antithrombin III concentrate]. 282 38

Enteric virus infections were studied in two children with congenital T-cell immunodeficiency. One patient (LC) with cartilage hair hypoplasia developed persistent diarrhea and malabsorption following acute gastroenteritis. Electron microscope (EM) examination of feces revealed excretion of rotavirus for more than 450 days with concurrent astrovirus infection for at least 225 days, associated with the persistent diarrhea. Prolonged infection with poliovirus type 2 following vaccination had previously been noted in this patient. The second patient (DT), with the CHARGE association and DiGeorge syndrome, had two episodes of loose stools. EM of fecal extracts demonstrated rotavirus excretion for at least 66 days following the initial episode. Virus-specific immune responses were assayed in these two patients. LC showed a poor serum neutralizing antibody response to polio vaccination, no detectable antibody response (by immune EM and ELISA) to rotavirus, and no detectable antibody response to astrovirus (by immune EM). Rotavirus specific cell mediated immunity was also not detectable. DT showed no detectable serum antibody response to rotavirus (by ELISA). Rotavirus isolates from both patients were found to be group A viruses and were further analyzed by polyacrylamide gel electrophoresis. Atypical genome profiles, with multiple additional bands between segments 3-7 of the normal rotavirus profile, were obtained throughout the course of each illness, including the earliest specimens available (day 41, LC; day 7, DT). These results indicate that chronic virus infection of the gut can occur in patients with T-cell immunodeficiency. Such chronic infection may be associated with persistent diarrhea and can cause considerable problems of management.
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PMID:Chronic enteric virus infection in two T-cell immunodeficient children. 283 34

Twenty-seven medicinal herbs reputed in ancient Chinese folklore to have anti-infective properties were extracted by boiling under reflux. The extracts were tested for inhibitory activity against the human immunodeficiency virus in the H9 cell line at concentrations nontoxic to growth of the H9 cells. Using a significant reduction (greater than 3 S. D. below the mean) in the percentage of cells positive for specific viral antigens in three successive assays as indicative of activity against the virus, 11 of the 27 extracts were found to be active. One of the extracts (Viola yedoensis) was studied in greater depth. At a subtoxic concentration, this extract shut off completely the growth of HIV in virtually all experiments. It did not inactivate HIV extracellularly, did not induce interferon and did not inhibit the growth of herpes simplex, polio or vesicular stomatitis viruses in human fibroblast culture. Chinese medicinal herbs appeared to be a rich source of potentially useful materials for the treatment of human immunodeficiency virus infection.
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PMID:Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs. 284 Aug 49

Current experience with the safety and efficacy of vaccines in infected children and adults is reviewed to examine the basis for decisions about routine immunisations of children infected with the human immunodeficiency virus (HIV). No adverse reactions to inactivated vaccines have been noted, but complications with live vaccines have been recorded with both BCG and smallpox. Limited experience with live poliomyelitis and measles vaccines in HIV-infected children has not yet shown any severe complications from these vaccines. Theoretical concerns that immunisation might accelerate the course of HIV infection are not supported by available data. Serological response to most inactivated and live vaccines is reduced in HIV-infected persons, and is related to the degree of immunosuppression present. Preliminary evidence suggests that the severity of some vaccine-preventable diseases is increased in HIV-infected children. This review finds general support for recommendations on immunisation of HIV-infected children that have been developed by the World Health Organisation.
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PMID:Human immunodeficiency virus infection and routine childhood immunisation. 288 50

A polyclonal T-cell receptor complex (TCR) expression defect (as detected with monoclonal antibody WT31) has been found in two children belonging to an otherwise healthy Spanish family. One of the sibs (V, who had been vaccinated with attenuated poliomyelitis virus) showed clinical signs of immunodeficiency with an autoimmune syndrome, but the other (older) sib (D, vaccinated with attenuated rubella, measles, mumps, and poliomyelitis viruses) has been symptomless throughout life. In contrast to both sibs' normal expression of other peripheral leucocyte markers, as measured by flow cytometry (including CD1, CD2, CD4, CD8, and CD16), only about 6% of CD2+ polyclonal T cells expressed surface antigen-specific T-cell receptor (Ti/WT31), and only about 23% weakly expressed surface CD3 determinants. On the remaining CD2+ T cells in each sib the expression of Ti and CD3 was undetectable; the defect in CD3 expression is very likely secondary to the defect in Ti expression. Natural killer (NK) activity was not increased in any of the sibs, ruling out a high content of NK cells among their CD2+ lymphocytes. Functional data indicate that CD3-mediated T-cell activation with anti-CD3 monoclonals and Ti-mediated responses to allogeneic and tetanus toxoid antigens were severely depressed, whereas activation via CD2 was normal in the T lymphocytes of both sibs. Genes encoding for Ti alpha, beta, and gamma chains did not show major alterations by southern blot analysis, and polyclonal beta chain genes rearrangements were detected in both children's T-cell blasts. Family clustering suggests a genetic pathogenesis, but linkage to HLA or other blood group markers has not been found. Sib V had a concomitant autoimmune disease and died after a severe autoimmune haemolytic anaemia, indicating a relationship between the TCR and generation of autoimmune clones. However, the resistance of both individuals to infection and to vaccination with attenuated viruses, and the fact that sib D has been symptomless to date questions the relative importance of the TCR in the immune response against infection, and suggests that alternative T-cell activation pathways and non-specific defence mechanisms (external surfaces--bound and/or cellular) may suffice under certain circumstances.
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PMID:An in vivo functional immune system lacking polyclonal T-cell surface expression of the CD3/Ti(WT31) complex. 296 74

Some significant studies reported in the world literature which provide a scientific basis for immunization policy for those children known to be infected with human immunodeficiency virus (HIV) are reviewed. The review covers current experience with immunization of children infected with HIV along with relevant data on immunization of HIV-infected adults and in vitro studies with vaccine antigens and HIV-infected cells. Live vaccines have been contraindicated in children with immunodeficiency diseases because of the potential for disseminated infection with either the viral or bacterial vaccine strain. The assessment of a similar risk in HIV-infected children is complicated by the fact that it is not always known whether HIV-infected children actually are immunodeficient when immunized. Generally, inactivated vaccines are not considered to present a risk to immunodeficient children, but questions have been raised regarding the potential for any immunization to accelerate the course of HIV infection. Consequently, the safety of inactivated vaccines must be considered also. Local reactions and disseminated disease have been describe in HIV-infected individuals. The rate of dissemination of BCG cannot be determined from the available case reports, but they suggest the possibility of an increased risk for this otherwise unusual complication of BCG immunization. Limited data suggest that live measles vaccine doses not cause severe complications in children with HIV infection. Both reports from the US and Europe have failed to document adverse reactions to either live oral or inactivated polio vaccines. No side effects of DPT vaccine were noted in 2 published reports from Europe and the US. Available data on immunogenicity in children and adults show that both primary and secondary antibody responses to immunization are attenuted in the presence of HIV infection. This is particularly the case when immunodeficiency is present. It has been difficult to assess vaccine efficacy in HIV-infected children from industrialized nations due to the relatively low incidence of both vaccine-preventable disease and HIV infection. Only preliminary studies on vaccine efficacy are available from developing nations. This review offers some general support for the recommendations on immunizations of HIV-infected children that were developed by the World Health Organization and the Advisory Committee on Immunization Practices of the US Public Health service. For asymptomatic HIV-infected children, both groups recommend continued administration of standard vaccines. For symptomatic HIV-infected children, both groups recommend continued administration of inactivated vaccines but differ in their recommendations on live vaccines.
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PMID:HIV infection and routine childhood immunization: a review. 332 88

Live virus vaccines can cause serious adverse reactions when administered to immunocompromised patients. Because children infected with human immunodeficiency virus (HIV) may be immunosuppressed, immunization of these children with live virus vaccines is a potential problem. A retrospective survey was conducted by the New York City Department of Health, with consultation from the Centers for Disease Control, to evaluate the frequency of serious adverse events following receipt of live vaccines among children with HIV infection receiving pediatric care in New York City and New Jersey. Outpatient records of 319 children being cared for by 16 participating physicians were reviewed. Of the 319 charts, 221 (69%) contained vaccination histories. Perinatal transmission of HIV infection was suspected for 208 (94%) of the 221 cases and infection via transfusion for the remaining 13 (6%). Of the 221 for whom immunization histories were available, 180 (81%) had received at least one dose of live oral polio vaccine and 70 (32%) had received measles, mumps, and rubella vaccine. There were 120 children for whom a temporal relationship between immunization and onset of symptoms of immunodeficiency could be seen; 46/120 had received at least one dose of oral polio vaccine and 23/45 had received measles, mumps, and rubella vaccine after onset of symptoms. Although follow-up of this population has been limited, there were no reports of serious adverse events such as typical or atypical measles, paralytic poliomyelitis, or aseptic meningitis in the month following vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Live virus vaccines in human immunodeficiency virus-infected children: a retrospective survey. 339 96

Five asymptomatic human immunodeficiency virus (HIV)-seropositive male homosexuals were immunized with the recall antigens tetanus toxoid (TT) and the three types of poliovirus present in diphtheria, tetanus, and polio vaccine. Four weeks after immunization, the in vivo response to booster immunization, the in vitro pokeweed mitogen (PWM)-induced IgG secretion, and the in vitro T cell-dependent and T cell-independent antigen-induced antibody response were assayed. Increase in serum antibody titer to TT and poliovirus was low and normal, respectively. In all five subjects studied, a high rate of spontaneous IgG production, including antibodies directed toward HIV was observed. Addition of PWM to the cultures induced suppression of the spontaneous IgG secretion. Only one donor showed a slightly increased IgG production after stimulation with PWM. Peripheral blood mononuclear cells of four of the five HIV-seropositive individuals did not produce TT, or poliovirus-specific antibodies when stimulated with the respective T cell-dependent antigens. However, stimulation of these peripheral blood mononuclear cells with TT coupled to agarose beads, which was shown to be T cell-independent, resulted in the generation of IgG anti-TT antibody-forming cells.
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PMID:Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation. 349 62


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