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Thematische Bibliographien / HIV (Viruses) Gene therapy

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Auswahl der wissenschaftlichen Literatur zum Thema „HIV (Viruses) Gene therapy“

Autor: Grafiati

Veröffentlicht am 4. Juni 2021

Zuletzt aktualisiert am 1. Februar 2022

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Zeitschriftenartikel zum Thema "HIV (Viruses) Gene therapy"

1

Hu, JinTing, YeWen Feng, Ping Ma und Yu Lai. „Coreceptor-Based Hematopoietic Stem Cell Gene Therapy for HIV Disease“. Current Stem Cell Research & Therapy 14, Nr. 7 (23.09.2019): 591–97. http://dx.doi.org/10.2174/1574888x14666190523094556.

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: Combination antiretroviral therapy (cART) has significantly reduced the mortality rate and morbidity, and has increased the life expectancy of the human immunodeficiency virus (HIV) infected patients. However, the current cART is incapable of eradicating viruses from the human body, and HIV remains one of the most notorious viruses mankind has ever faced. HIV-1 enters target cells through the binding of gp120 viral protein to a CD4 receptor and then to a coreceptor, C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Individuals homozygous for a 32-bp deletion in the CCR5 allele, CCR5Δ32, are almost completely resistant to HIV-1 acquisition. Moreover, several of natural CXCR4 mutants which have been identified can reduce HIV-1 entry without impairing either ligand binding or signaling. In order to get rid of indefinite treatment for HIV patients, there is a growing interest in creating an HIV-resistant immune system through the use of CCR5 and CXCR4-modified hematopoietic stem cells (HSCs). Proof of concept for this approach has been provided in the instance of “Berlin patient” transplanted with allogeneic stem cells from a donor with homozygosity for the CCR5Δ32 deletion. Here, we review the progress of coreceptor-based HSC gene therapy for HIV disease and present new strategies.

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2

Weinberger, Leor S., David V. Schaffer und Adam P. Arkin. „Theoretical Design of a Gene Therapy To Prevent AIDS but Not Human Immunodeficiency Virus Type 1 Infection“. Journal of Virology 77, Nr. 18 (15.09.2003): 10028–36. http://dx.doi.org/10.1128/jvi.77.18.10028-10036.2003.

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ABSTRACT Recent reports confirm that, due to the presence of long-lived, latently infected cell populations, eradication of human immunodeficiency virus type 1 (HIV-1) from infected patients by using antiretroviral drugs will be exceedingly difficult. An alternative to virus eradication may be to use gene therapy to induce a pseudo-latent state in virus-producing cells, thus transforming HIV-1 into a lifelong, but manageable, virus. Conditionally replicating HIV-1 (crHIV-1) gene therapy vectors provide an avenue for subduing HIV-1 expression in infected cells (by creating a parasite, crHIV-1, of the parasite HIV-1), potentially reducing the HIV-1 set point and delaying AIDS onset. Development of crHIV-1 vectors has proceeded in vitro, but the requirements for a crHIV-1 vector to proliferate and persist in vivo have not been explored. We expand a widely accepted mathematical model of HIV-1 in vivo dynamics to include a crHIV-1 gene therapy virus and derive a simple criterion for designing crHIV-1 viruses that will persist in vivo. The model introduces only two new parameters—HIV-1 inhibition and crHIV-1 production—and both can be experimentally engineered and controlled. Analysis demonstrates that crHIV-1 gene therapy can indefinitely reduce HIV-1 set point to levels comparable to those achieved with highly active antiretroviral therapy, provided crHIV-1 production is more efficient than HIV-1. Paradoxically, highly efficient therapeutic inhibition of HIV-1 was found to be disadvantageous. Thus, the field may benefit by shifting the search for more potent antiviral genes toward engineering optimized therapy viruses that package ultraefficiently while downregulating viral production moderately.

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3

Das, Atze T., Thijn R. Brummelkamp, Ellen M. Westerhout, Monique Vink, Mandy Madiredjo, René Bernards und Ben Berkhout. „Human Immunodeficiency Virus Type 1 Escapes from RNA Interference-Mediated Inhibition“. Journal of Virology 78, Nr. 5 (01.03.2004): 2601–5. http://dx.doi.org/10.1128/jvi.78.5.2601-2605.2004.

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ABSTRACT Short-term assays have suggested that RNA interference (RNAi) may be a powerful new method for intracellular immunization against human immunodeficiency virus type 1 (HIV-1) infection. However, RNAi has not yet been shown to protect cells against HIV-1 in long-term virus replication assays. We stably introduced vectors expressing small interfering RNAs (siRNAs) directed against the HIV-1 genome into human T cells by retroviral transduction. We report here that an siRNA directed against the viral Nef gene (siRNA-Nef) confers resistance to HIV-1 replication. This block in replication is not absolute, and HIV-1 escape variants that were no longer inhibited by siRNA-Nef appeared after several weeks of culture. These RNAi-resistant viruses contained nucleotide substitutions or deletions in the Nef gene that modified or deleted the siRNA-Nef target sequence. These results demonstrate that efficient inhibition of HIV-1 replication through RNAi is possible in stably transduced cells. Therefore, RNAi could become a realistic gene therapy approach with which to overcome the devastating effect of HIV-1 on the immune system. However, as is known for antiviral drug therapy against HIV-1, antiviral approaches involving RNAi should be used in a combined fashion to prevent the emergence of resistant viruses.

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Bacheler, Lee, Susan Jeffrey, George Hanna, Richard D'Aquila, Lany Wallace, Kelly Logue, Beverly Cordova et al. „Genotypic Correlates of Phenotypic Resistance to Efavirenz in Virus Isolates from Patients Failing Nonnucleoside Reverse Transcriptase Inhibitor Therapy“. Journal of Virology 75, Nr. 11 (01.06.2001): 4999–5008. http://dx.doi.org/10.1128/jvi.75.11.4999-5008.2001.

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ABSTRACT Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear.

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Sakkhachornphop, Supachai, Sudarat Hadpech, Tanchanok Wisitponchai, Chansunee Panto, Doungnapa Kantamala, Utaiwan Utaipat, Jutarat Praparattanapan et al. „Broad-Spectrum Antiviral Activity of an Ankyrin Repeat Protein on Viral Assembly against Chimeric NL4-3 Viruses Carrying Gag/PR Derived from Circulating Strains among Northern Thai Patients“. Viruses 10, Nr. 11 (13.11.2018): 625. http://dx.doi.org/10.3390/v10110625.

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Certain proteins have demonstrated proficient human immunodeficiency virus (HIV-1) life cycle disturbance. Recently, the ankyrin repeat protein targeting the HIV-1 capsid, AnkGAG1D4, showed a negative effect on the viral assembly of the HIV-1NL4-3 laboratory strain. To extend its potential for future clinical application, the activity of AnkGAG1D4 in the inhibition of other HIV-1 circulating strains was evaluated. Chimeric NL4-3 viruses carrying patient-derived Gag/PR-coding regions were generated from 131 antiretroviral drug-naïve HIV-1 infected individuals in northern Thailand during 2001–2012. SupT1, a stable T-cell line expressing AnkGAG1D4 and ankyrin non-binding control (AnkA32D3), were challenged with these chimeric viruses. The p24CA sequences were analysed and classified using the K-means clustering method. Among all the classes of virus classified using the p24CA sequences, SupT1/AnkGAG1D4 demonstrated significantly lower levels of p24CA than SupT1/AnkA32D3, which was found to correlate with the syncytia formation. This result suggests that AnkGAG1D4 can significantly interfere with the chimeric viruses derived from patients with different sequences of the p24CA domain. It supports the possibility of ankyrin-based therapy as a broad alternative therapeutic molecule for HIV-1 gene therapy in the future.

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Manisha. B. Shinde, Dr. Archana D. Kajale, Dr. Madhuri A. Channawar und Dr. Shilpa R. Gawande. „Vector-mediated cancer gene therapy: A review“. GSC Biological and Pharmaceutical Sciences 13, Nr. 2 (30.11.2020): 152–65. http://dx.doi.org/10.30574/gscbps.2020.13.2.0368.

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Gene therapy is the transfer of genetic material to cure a disease or at least to improve the clinical status of a patient. One of the basic concepts of gene therapy is to transform viruses into genetic shuttles, which will deliver the gene of interest into the target cells. Safe methods have been devised to do this, using several viral and non-viral vectors. Two main approaches emerged: in vivo modification and ex vivo modification. Retrovirus, adenovirus, adenoassociated virus are suitable for gene therapeutic approaches which are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and their large capacity for therapeutic DNA. The most commonly used DNA virus vectors are based on adenoviruses and adeno-associated viruses. An example of gene-knockout mediated gene therapy is the knockout of the human CCR5 gene in T-cells in order to control HIV infection. To improve the function of non-viral vectors, the addition of viral functions such as receptor mediated uptake and nuclear translocation of DNA may finally lead to the development of an artificial virus. Gene transfer protocols have been approved for human use in inherited diseases, cancers and acquired disorders. Although the available vector systems are able to deliver genes in vivo into cells, the ideal delivery vehicle has not been found. Thus, the present viral vectors should be used only with great caution in human beings and further progress in vector development is necessary.

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Martinez, Miguel Angel, Maria Nevot, Ana Jordan-Paiz und Sandra Franco. „Similarities between Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Genetic and Phenotypic Protease Quasispecies Diversity“. Journal of Virology 89, Nr. 19 (15.07.2015): 9758–64. http://dx.doi.org/10.1128/jvi.01097-15.

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ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are two highly variable RNA viruses that cause chronic infections in humans. Although HCV likely preceded the AIDS epidemic by some decades, the global spread of both viruses is a relatively recent event. Nevertheless, HCV global diversity is higher than that of HIV-1. To identify differences in mutant diversity, we compared the HIV-1 protease and HCV NS3 protease quasispecies. Three protease gene quasispecies samples per virus, isolated from a total of six infected patients, were genetically and phenotypically analyzed at high resolution (HIV-1, 308 individual clones; HCV, 299 clones). Single-nucleotide variant frequency did not differ between quasispecies from the two viruses (HIV-1, 2.4 × 10−3± 0.4 × 10−3; HCV, 2.1 × 10−3± 0.5 × 10−3) (P= 0.1680). The proportion of synonymous substitutions to potential synonymous sites was similar (3.667 ± 0.6667 and 2.183 ± 0.9048, respectively) (P= 0.2573), and Shannon's entropy values did not differ between HIV-1 and HCV (0.84 ± 0.02 and 0.83 ± 0.12, respectively) (P= 0.9408). Of note, 65% (HIV-1) and 67% (HCV) of the analyzed enzymes displayed detectable protease activity, suggesting that both proteases have a similar mutational robustness. In both viruses, there was a rugged protease enzymatic activity landscape characterized by a sharp peak, representing the master sequence, surrounded by a collection of diverse variants present at lower frequencies. These results indicate that nucleotide quasispecies diversification during chronic infection is not responsible for the higher worldwide genetic diversity observed in HCV.IMPORTANCEHCV global diversity is higher than that of HIV-1. We asked whether HCV genetic diversification during infection is responsible for the higher worldwide genetic diversity observed in HCV. To this end, we analyzed and compared the genotype and enzymatic activities of HIV-1 and HCV protease quasispecies existing in infected individuals. Our results indicate that HIV-1 and HCV protease quasispecies have very similar genetic diversity and comparable rugged enzymatic activity landscapes. Therapy for HCV has expanded, with new therapeutic agents such as the direct-acting antivirals (DAAs). DAAs, which target HCV NS3 protease and other virus proteins, have improved cure rates. However, major questions remain to be elucidated regarding the virologic correlates of HCV eradication. The findings shown here may help our understanding of the different therapeutic responses observed during chronic HCV infection.

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Bailey, Justin R., Ahmad R. Sedaghat, Tara Kieffer, Timothy Brennan, Patricia K. Lee, Megan Wind-Rotolo, Christine M. Haggerty et al. „Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells“. Journal of Virology 80, Nr. 13 (01.07.2006): 6441–57. http://dx.doi.org/10.1128/jvi.00591-06.

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ABSTRACT Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4+ T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4+ T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4+ T cells by pol gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4+ T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of pol sequences in resting CD4+ T cells, the residual viremia was dominated by a homogeneous population of viruses with identical pol sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the env gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4+ T cells.

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Saunders, Kevin O., Lingshu Wang, M. Gordon Joyce, Zhi-Yong Yang, Alejandro B. Balazs, Cheng Cheng, Sung-Youl Ko et al. „Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection“. Journal of Virology 89, Nr. 16 (03.06.2015): 8334–45. http://dx.doi.org/10.1128/jvi.00908-15.

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ABSTRACTBroadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 μg/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled.IMPORTANCESustained interventions that can prevent HIV-1 infection are needed to halt the spread of the HIV-1 pandemic. The protective capacity of anti-HIV antibody gene therapy has been established in mouse models of HIV-1 infection but has not been established for primates. We show here a proof-of-concept that gene transfer of anti-HIV antibody genes can protect against infection by viruses that cause AIDS in primates when host immune responses are controlled.

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Styczyński, Jan. „ABC of viral infections in hematology: focus on herpesviruses“. Acta Haematologica Polonica 50, Nr. 3 (28.09.2019): 159–66. http://dx.doi.org/10.2478/ahp-2019-0026.

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AbstractViruses are a form of life that possess genes but do not have a cellular structure. Viruses do not have their own metabolism, and they require a host cell to make new products; therefore, they cannot naturally reproduce outside a host cell. The objective of this paper is to present the basic practical clinical roles of viruses in patients with hematological diseases including malignancies and non-malignan- cies, as well as those undergoing hematopoietic cell transplantation (HCT), with the focus on herpesviruses causing latent infections in severely immunocompromised patients. From the hematologist point of view, viruses can play a major role in four conditions: causing infections; causing lymphoproliferations and/or malignancies; causing (pan)cytopenia; and used as vectors in treatment (e.g., gene therapy, CAR-T cells). Taking into account the role of viruses in hematology, infection is the most frequent condition. Among DNA viruses, the highest morbidity potential for human is expressed by Herpesviridiae (herpesviruses), Adenoviridae (adenovirus; ADV), Polyomavirus (BKV, JCV), and Bocavirus. RNA viruses can play a role in pathogenesis of different clinical conditions and diseases: lymphoproliferative disorders and malignancy, possibly causing NHL, AML, MDS, and others (HCV, HIV, and others); pancytopenia and aplastic anemia (HIV, HCV, Dengue virus); respiratory infections (community-acquired respiratory virus infections; CARV) caused by Orthomyxoviruses (e.g. influenza A/B), Paramyxoviruses (e.g. human parainfluenza virus PIV-1, -2, -3, and -4; respiratory syncytial virus RSV-A and -B), picornaviruses (e.g., human rhinovirus), coronaviruses (e.g., human coronavirus), Pneumoviridiae (e.g., human metapneumovirus), and potentially other viruses.

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Dissertationen zum Thema "HIV (Viruses) Gene therapy"

1

Fuller, Maria. „A gene transfer system derived from human immunodeficiency virus type 1 (HIV-1)“. Title page, table of contents, list of abbreviations and epitome only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phf9669.pdf.

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Grzybowski, Brad. „A pseudotyped viral vector : hPIV3-HIV-1“. Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/20932.

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3

Gelinas, Jean-Francois. „Enhancement of lentiviral vector production through alteration of virus-cell interactions“. Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:9921b8b4-e2b5-4eec-9efc-6036765c8d55.

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Gene therapy is the introduction or alteration of genetic material with the intention to treat disease. To support this aim, viruses have been modified, with elements linked to viral pathogenicity removed from their genome and replaced by the genetic material to be delivered. Gene therapy vectors based on lentiviruses have many advantages, such as the ability to transduce non-dividing cells and to target specific cell types via pseudotyping. They have been successfully used in ex vivo clinical trials for several haematopoietic stem cell disorders. Lentiviral vectors, however, suffer from substantially lower titres than the more popular adeno-associated virus (AAV)-based vectors and therefore have limited applicability for in vivo gene therapy which requires much greater quantities of virus. The main aim of this thesis was to investigate strategies to improve lentiviral vector productivity during manufacture, in order to increase the likelihood of lentiviruses being adopted for disease treatment. Initial experiments were based on the lentiviral vector manufacturing process currently being developed by the United Kingdom Cystic Fibrosis Gene Therapy Consortium for the generation of highly concentrated, purified lentivirus for clinical use. Supplementation of FreeStyle 293 Expression Medium used during upstream processing was attempted, but none of the assessed supplements led to significant increases in lentiviral vector production. Investigation into intrinsic immunity to viral infection indicated that over-expression of the protein kinase RNA-activated (PKR) led to lower production titres, but over-expression of its inhibitors was not successful at increasing titres. The focus then shifted to reducing, or 'knocking-down', inhibitory factors present in the host cells, which could adversely affect viral titres. Investigation of the published HIV-1 literature revealed a possible 152 candidate inhibitory factors described as having a negative impact on HIV-1 replication in the late stages of the life cycle of the virus. A novel siRNA screen was developed to assess the effect of âknock-down' of inhibitory factors on lentiviral vector titre. Application of the screen to 89 candidate inhibitory factors identified nine genes which, when knocked-down, resulted in increased lentiviral vector production by more than 40%. Further work will be necessary to understand the role of the inhibitory factors in lentiviral vector production, but novel cell lines in which genes encoding these factors have been permanently deleted from producer cells could lead to higher titres, reducing costs in the manufacture of lentiviral vectors and making in vivo gene therapy more feasible from a health economics perspective.

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Elmén, Joacim. „Nucleic acid based therapeutic approaches /“. Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-047-8/.

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Morin, Nicolas. „Expression of mutated HIV-1 Gag-Pol proteins and their effects on virus replication and infectiousness, implications for gene therapy“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0015/MQ37152.pdf.

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Mackler, Randi Michelle. „Understanding Prototype Foamy Virus Integrase Site Selection, Activity, and Stability“. The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134.

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ALVES, Neyla Maria Pereira. „Influência de polimorfismos de base única (SNPs) no gene do receptor de vitamina D (VDR) na resposta à Terapia Antirretroviral (TARV) de pessoas vivendo com Vírus da Imunodeficiência Humana tipo 1 (HIV-1)“. Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/16120.

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Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-03-22T18:32:27Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Neyla Alves_Versão digital.pdf: 1629049 bytes, checksum: aa72b7e3881142a178e5534aa4064d95 (MD5)
Made available in DSpace on 2016-03-22T18:32:27Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Neyla Alves_Versão digital.pdf: 1629049 bytes, checksum: aa72b7e3881142a178e5534aa4064d95 (MD5) Previous issue date: 2015-03-02
CAPES
CNPq
HIV/aids (Vírus da Imunodeficiência Humana/aids) é considerado uma pandemia, envolvendo mais de 70 milhões de infecções e 35 milhões de mortes desde o primeiro relato na década de 80. O HIV tipo 1 (HIV-1) infecta principalmente linfócitos T CD4+ e linhagens de macrófagos, tendo sua patogenicidade definida pela depleção de LT CD4+. Além disso, a condição de infecção por HIV-1 é bastante complexa e dependente de diversos fatores relacionados à variabilidade dos indivíduos no que diz respeito à suscetibilidade à infecção e à progressão para a aids, sendo observada a ativação imunológica generalizada. Envolvida na modulação das respostas imunes inata e adaptativa encontra-se a vitamina D, que desempenha papel no metabolismo mineral e apresenta efeito pleiotrópico no crescimento e diferenciação celulares. Seus efeitos imunológicos são dados a partir da ligação com o receptor de vitamina D (VDR) de diversas células, regulando a liberação de citocinas, a função e proliferação de linfócitos T e a produção de peptídeos antimicrobianos como a catelicidina. O VDR atua modulando a ação dessa vitamina induzindo a resposta imune local e variações genéticas presentes no gene codificador do VDR podem levar à diminuição de sua atividade e, consequentemente, ao prejuízo para o papel da vitamina D. Nos indivíduos infectados pelo HIV, os níveis de deficiência dessa vitamina são altos e fatores como raça, insuficiência renal, pouca exposição à luz ultravioleta e exposição as drogas anti-HIV, como o Efavirenz, estão associados a essa deficiência, respectivamente, sendo determinantes para a susceptibilidade à infecção pelo HIV e a predição da progressão da doença. Sendo assim, neste trabalho foram estudados seis polimorfismos de base única (SNPs) (rs3890733, rs476048, rs1540339, rs2248098, rs2228570 e rs11568820) presentes no gene do receptor de vitamina D (VDR) e sua influência na resposta dos pacientes à Terapia Antirretroviral (TARV). Foram recrutados 107 pacientes acompanhados e tratados no Hospital Dia do Instituto de Medicina Integral Professor Fernando Figueira (IMIP), subdivididos em quatro grupos: I- Sucesso Terapêutico, II- Falha Terapêutica, III- Sucesso Imunológico, IV- Falha Imunológica, e analisadas variáveis clínicas e epidemiológicas, como gênero, idade, peso e etnia. Não foram observadas associações estatísticas nas análises isoladas entre os polimorfismos dos genes do VDR com a falha virológica ou a resposta imunológica. Porém, nas análises multivariadas, o genótipo C/C do rs1540339 mostrou-se associado com o gênero no sucesso virológico (OR=0,08, p=0,04). Em adição, a análise envolvendo peso, etnia e gênero e o rs3890733 mostrou associação com a resposta imunológica para os genótipos C/C e T/T no modelo sobredominante (OR=0,21, p=0,024). Os resultados indicam a importância do receptor de vitamina D em infecções por HIV-1 e poderão contribuir para o entendimento da variabilidade das respostas dos pacientes à TARV.
HIV/aids (Human Immunodeficiency Virus/aids) is considered a pandemic, involving more than 70 million infections and 35 million deaths since the first report in the 80’s. HIV type 1 (HIV-1) infects mainly T lymphocytes CD4 + and macrophage lineages, and their pathogenicity is defined by the depletion of CD4 +. Furthermore, the condition of HIV- 1 infection is very complex and dependent on many factors related to the individual variability, regarding the susceptibility to infection and progression to AIDS, generalized immune activation being observed. Involved in the modulation of innate and adaptive immune responses is vitamin D, which plays a role in mineral metabolism and has pleiotropic effects on cell growth and differentiation. Their immune effects are data from binding to the vitamin D receptor (VDR) in various cells, regulating the release of cytokines, the function and proliferation of T lymphocytes and the production of antimicrobial peptides as cathelicidin. The VDR acts modulating the action of vitamin D by inducing local immune responses and genetic variations present in the VDR encoding gene can lead to reduction of its activity and consequently, disfunction in the role of vitamin D. In HIV-infected individuals, this vitamin deficiency levels are high and factors such as race, kidney failure, lower exposure to ultraviolet light and exposure to anti- HIV drugs, such as Efavirenz, are associated with this deficiency, being determinants on the susceptibility to HIV infection as well as prediction of disease progression. Therefore, in this work we studied six single nucleotide polymorphisms (SNPs) (rs3890733, rs476048, rs1540339, rs2248098, rs2228570 and rs11568820) present in the D vitamin receptor gene (VDR) and its influence on patients’ response to Antiretroviral Therapy (ART). We recruited 107 patients followed from the Hospital Day Integrative Medicine Institute Professor Fernando Figueira (IMIP), subdivided into four groups: I. Therapeutic Success, II. Therapeutic Failure, III. Immune Success, IV. Immune Failure, and analyzed clinical and epidemiological variables, such as gender, age, weight and ethnicity. No statistically significant associations were observed in the isolated analyzes between polymorphisms of the VDR gene with therapeutic failure or immune response. However, in multivariate analyzes, the rs1540339 C/C genotype was associated with gender in therapeutic success (OR = 0.08, p = 0.04). In addition, analysis involving weight, ethnicity and gender and the rs3890733 showed association with the immune response to the C/C genotype and T/T in overdominant model (OR = 0.21, p = 0.024). The results indicate the importance of vitamin D receptor in HIV- 1 infections and may contribute to the understanding of variability of patient’s various responses to ART.

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Costa, Matthew R. „FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation“. eScholarship@UMMS, 2010. http://escholarship.umassmed.edu/gsbs_diss/866.

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Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc mediated effector functions. I developed a protocol for the production and analysis of HIV-1 Env-specific human monoclonal antibodies (mAbs) isolated from these DP6-001 vaccinees. By utilizing a labeled gp120 bait to isolate Env specific B cells, paired heavy and light chain immunoglobulin (Ig) genes were cloned and allowed for the production of monoclonal antibodies with specificity for gp120. By using this protocol, 13 isolated mAbs from four DP6-001 vaccinees showed broad binding activities to gp120 proteins of diverse subtypes, both autologous and heterologous to vaccine immunogens, with mostly conformational epitopes and a few V3 and C5 specific mAbs. Equally cross-reactive Fc-mediated functional activities, including ADCC and antibody dependent cellular phagocytosis (ADCP), were present with both immune sera and isolated mAbs, confirming the induction of non-neutralizing functional antibodies by the DNA prime- protein boost vaccination. Elicitation of broadly reactive mAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV-1 vaccine design.

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Costa, Matthew R. „FC Receptor-Mediated Activities of Env-Specific Monoclonal Antibodies Generated from Human Volunteers Receiving a DNA Prime-Protein Boost HIV Vaccine: A Dissertation“. eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/866.

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Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc mediated effector functions. I developed a protocol for the production and analysis of HIV-1 Env-specific human monoclonal antibodies (mAbs) isolated from these DP6-001 vaccinees. By utilizing a labeled gp120 bait to isolate Env specific B cells, paired heavy and light chain immunoglobulin (Ig) genes were cloned and allowed for the production of monoclonal antibodies with specificity for gp120. By using this protocol, 13 isolated mAbs from four DP6-001 vaccinees showed broad binding activities to gp120 proteins of diverse subtypes, both autologous and heterologous to vaccine immunogens, with mostly conformational epitopes and a few V3 and C5 specific mAbs. Equally cross-reactive Fc-mediated functional activities, including ADCC and antibody dependent cellular phagocytosis (ADCP), were present with both immune sera and isolated mAbs, confirming the induction of non-neutralizing functional antibodies by the DNA prime- protein boost vaccination. Elicitation of broadly reactive mAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV-1 vaccine design.

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Chen, Yuxin. „Characterization of Envelope-Specific Antibody Response Elicited by HIV-1 Vaccines: A Dissertation“. eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/760.

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Despite 30 years of intensive research，an effective human immunodeficiency virus (HIV) vaccine still remains elusive. The desirable immune response capable of providing protection against HIV acquisition is still not clear. The accumulating evidence learned from a recent vaccine efficacy correlate study not only confirmed the importance of antibody responses, but also highlighted potential protective functions of antibodies with a broad repertoire of HIV-1 epitope specificities and a wide range of different antiviral mechanisms. This necessitates a deep understanding of the complexity and diversity of antibody responses elicited by HIV-1 vaccines. My dissertation characterizes antibody response profiles of HIV-1 Env antibodies elicited by several novel immunogens or different immunization regimens, in terms of magnitude, persistence, epitope specificity, binding affinity, and biological function. First, to overcome the challenge of studying polyclonal sera without established assays, we expanded a novel platform to isolate Env-specific Rabbit mAbs (RmAb) elicited by DNA prime-protein boost immunization. These RmAbs revealed diverse epitope specificity and cross-reactivity against multiple gp120 antigens from more than one subtype, and several had potent and broad neutralizing activities against sensitive Tier 1 viruses. Further, structural analysis of two V3 mAbs demonstrated that a slight shift of the V3 epitope might have a dramatic impact on their neutralization activity. All of these observations provide a useful tool to study the induction of a desired type of antibody by different immunogens or different immunization regimens. Since heavily glycosylated HIV Env protein is a critical component of an HIV vaccine, we wanted to determine the impact of the HIV Env-associated glycan shield on antibody responses. We were able to produce Env proteins with a selective and homogeneous pattern of N-glycosylation using a glycoengineered yeast cell line. Antigenicity of these novel Env proteins was examined by well-characterized human mAbs. Immunogenicity studies showed that they were immunogenic and elicited gp120- specific antibody responses. More significantly, sera elicited by glycan-modified gp120 protein immunogens revealed better neutralizing activities and increased diversity of epitopes compared to sera elicited by traditional gp120 produced in Chinese Hamster Ovary (CHO) cells. Further, we examined the impact of the delivery order of DNA and protein immunization on antibody responses. We found that DNA prime-protein boost induced a comparable level of Env-specific binding Abs at the peak immunogenicity point to codelivery of DNA. However, antibody responses from DNA prime-protein boost had high avidity and diverse specificities, which improved potency and breadth of neutralizing Abs against Tier 1 viruses. Our data indicate that DNA vaccine priming of the immune system is essential for generation of high-quality antibodies. Additionally, we determined the relative immunogenicity of gp120 and gp160 Env in the context of DNA prime-protein boost vaccination to induce high-quality antibody responses. Immunized sera from gp120 DNA primed animals, but not those primed with gp160 DNA, presented with distinct antibody repertoire specificities, a high magnitude of CD4 binding site-directed binding capabilities as well as neutralizing activities. We confirmed the importance of using the gp120 Env form at the DNA priming phase, which directly determined the quality of antibody response.

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Bücher zum Thema "HIV (Viruses) Gene therapy"

1

Bauer, Gerhard, und Joseph S. Anderson. Gene Therapy for HIV. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1.

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Vos, Jean-Michel H., Hrsg. Viruses in Human Gene Therapy. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0555-2.

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Singwi, Sanjeev. HIV gene therapy using nucleases. Ottawa: National Library of Canada, 1996.

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Smith, Clay. Gene Therapy for HIV Infection. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-662-11821-4.

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Hengge, Ulrich R. Immunotreatment and gene therapy of HIV infection. Bremen: Uni-Med, 2004.

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Berkhout, Ben, Hildegund C. J. Ertl und Marc S. Weinberg, Hrsg. Gene Therapy for HIV and Chronic Infections. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2432-5.

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Virology, Conference on. HIV and other highly pathogenic viruses. San Diego: Academic Press, 1988.

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Canada, Canada Health and Welfare. Therapy and management of CMV in patients with HIV infection/ by Susan M.King. Ottawa: Health and Welfare Canada, 1990.

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Lombardi, Rocco Anthony. GAG and ENV trans-dominant mutants for use in ANTI-HIV-1 gene therapy. Ottawa: National Library of Canada, 1996.

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Catalán, José. Psychological medicine of HIV infection. Oxford: Oxford University Press, 1995.

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Buchteile zum Thema "HIV (Viruses) Gene therapy"

1

Morgan, Richard A. „Gene Therapy“. In Immunology of HIV Infection, 577–94. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4899-0191-0_30.

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Bauer, Gerhard, und Joseph S. Anderson. „Gene Therapy Vectors“. In Gene Therapy for HIV, 27–33. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_4.

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Bauer, Gerhard, und Joseph S. Anderson. „Principles of Gene Therapy“. In Gene Therapy for HIV, 1–8. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_1.

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Bauer, Gerhard, und Joseph S. Anderson. „History of Gene Therapy“. In Gene Therapy for HIV, 9–15. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_2.

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Bohnlein, Ernst. „HIV Gene Therapy: Current Status and Its Role in Therapy“. In Gene Therapy, 91–101. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-72160-1_10.

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Bauer, Gerhard, und Joseph S. Anderson. „Principles of HIV Gene Therapy“. In Gene Therapy for HIV, 17–25. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_3.

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Bauer, Gerhard, und Joseph S. Anderson. „Stem Cells for HIV Gene Therapy“. In Gene Therapy for HIV, 35–40. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_5.

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Bauer, Gerhard, und Joseph S. Anderson. „Animal Models Used in HIV Gene Therapy“. In Gene Therapy for HIV, 41–47. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_6.

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Bauer, Gerhard, und Joseph S. Anderson. „Manufacturing of a GMP Grade Product for HIV Gene Therapy“. In Gene Therapy for HIV, 49–54. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_7.

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Bauer, Gerhard, und Joseph S. Anderson. „Clinical Applications of HIV Gene Therapy“. In Gene Therapy for HIV, 55–62. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0434-1_8.

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Konferenzberichte zum Thema "HIV (Viruses) Gene therapy"

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Noy, Ariela. „Abstract PL04-02: HIV malignancies: From despair to gene therapy“. In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-pl04-02.

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Noy, Ariela. „Abstract PL04-02: HIV malignancies: From despair to gene therapy“. In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-pl04-02.

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Miyahara, Hideo, Yuta Kurashina, Yuki Ogawa, Ayumu Kurihara, Tomohiko Yoshida, Hirotaka James Okano, Masato Fujioka und Hiroaki Onoe. „Hierarchical Hydrogel Drug Delivery System Enables Controlled Release of Adeno-Associated Viruses for Gene Therapy“. In 2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS). IEEE, 2019. http://dx.doi.org/10.1109/memsys.2019.8870781.

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Martini, Sabrina V., Adriana L. Silva, Miquéias Lopes-Pacheco, Hilda Petrs-Silva, Rafael Linden, Patricia R. M. Rocco und Marcelo M. Morales. „The Efficiency Of Tyrosine-Mutant Adeno-Associated Viruses (AAVs) Serotype Vectors In Pulmonary Gene Therapy“. In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4975.

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Schimpf, Kl, H. H. Brackmann, D. Bock, G. Landbeck, E. Lechler und H. Vinazzer. „NO ANTI-HIV SEROCONVERSION AFTER REPLACEMENT THERAPY WITH STEAM-TREATED FACTOR VIII CONCENTRATE. A STUDY OF 60 PATIENTS WITH HEMOPHILIA A AND VON WILLEBRAND'S DISEASE“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644054.

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Transmission of hepatitis viruses and HIV has proven to be a risk of replacement therapy. Since Dec. 1983 factor VIII concentrates in which viruses are inactivated by steam-treatment (Factor VIII TIM 3 or S-TIM 3) are available for therapy. As they are manufactured by 80% from US plasma it was necessary to prove that they do not transmit HIV. For ethical reasons it is not possible to treat control groups of patients with non-virus- inactivated concentrate. Non-transmission of HIV can, therefore, only be proven if anti-HIV seroconversion does not occur in larger groups of patients treated with this type of product. We collected data from 60 patients, who were “virgin” (24) or, if pre-treated, anti-HIV seronegative. Therapy with Factor VIII TIM 3 or S-TIM 3 was started between Sept. 1984 and April 1986. The median length of observation till the last anti-HIV testing was 12 (6 - 24) months. The median total dosage of Factor VIII was 56,500 (500 - 427,500) IU, the median patient age was 20 (1 - 61) years. In none of the patients anti-HIV seroconversion (ELISA test) was observed. According to the rule ofthree the upper 95% confidence limit for random sample of 60 cases with zero events would be 3/60 or 5%.

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Schimpf, K. l., B. Kraus, W. Kreuz, H. H. Brackmann, F. Haschke und W. Schramm. „NO ANTI-HIV SEROCONVERSION AFTER REPLACEMENT THERAPY WITH PASTEURIZED F VIII CONCENTRATE. A STUDY OF 151 PATIENTS WITH HEMOPHILIA A OR VON WILLEBRAND'S DISEASE“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643973.

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Transmission of hepatitis viruses and HIV has proven to be a risk of replacement therapy in hemophilia. As regards F VIII products a concentrate (Hemate HS or P) in which viruses are inactivated by heat-treatment over 10 hours at 60° C in aqueous solution is available since 1979. Our clinical studies have shown that this product does not transmit HBV and HNANBV. As the product was manufactured by 80% from US plasma it was necessary to prove that it also does not transmit HIV. As it is, for ethical reasons, not possible to treat a control group with non-virus-inactivated F VIII, non-transmission of HIV can only proven if anti-HIV seroconversion does not occur in larger groups of patients treated exclusively with this virus-inactivated product.We collected data from 151 patients treated with Hemate HS (P) who had never before received blood or blood products. Therapy was started between Feb. 1979 and Jan. 1986 (median July 7,1983). The median length of observation till the last anti-HIV testing was 24 (3 - 83) months. 112 patients were observed longer than 13 months. The median total dosage was 17,000 (500 -2,155,375) IU of F VIII, the median patient age was 6 (0,5 - 68) years. In none of these patients anti-HIV seroconversion (ELISA test) was observed. According to the rule of three, the upper 95% confidence limit for a random sample of 60 cases with zero events would be 3/60 or 5%. For greater numbers of n cases, as in our study, the range of confidence narrows increasingly. The period of observation of this study is hitherto the longest.

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Addiego, J. E., P. Bailey, M. Bradley, S. Courter und M. Lee. „RECOVERY AND SURVIVAL STUDIES OF A NEW FACTOR VIII PRODUCT“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644052.

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Lyophilized protein concentrates are the international treatment of choice to manage bleeding in hemophiliacs. These pooled plasma products, however, expose the recipient of treatment to an increased risk of viral infections. While current manufacturing techniques of these products appear to be effective in eradicating the human immunodeficiency virus (HIV), transmission of other viruses, especially non-A/non-B (NANB) hepatitis, is still a majoor complication of concentrate therapy. Hyland Therapeutics Division Travenol Laboratories, Inc., has developed a new process using the techniques of immunoaffinity chromatography and organic solvent/detergent treatment to prepare a high specific activity product; Antihemophilic Factor (Human), Method M (AHF-M); that may render it free of pathogenic viruses. To determine the recovery and half-life of factor VIII in this product five severe hemophiliacs in a nonbleeding state were given! 50 U/kg of M-AHF and 50 U/kg of a currently licensed factor concentrate (HEMOFILe CT) in a crossover blinded study with a seven day interval between the respective infusions. The table below shows the recovery and half-life results for the five patients studiedThe factor VIII recoveries and half-lifes were similar for both products. No significant adverse clinical reactions were detected in any patient either during or after their infusions. This product appears to produce adequate circulating levels of factor VIII. It also appears to be safe for administration in humans. Further studies are on-going to test the overall efficacy of this product and to confirm that the manufacturing process is effective in eliminating pathogenic viruses

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Karges, H. E., P. Fuhge und N. Heimburger. „PROPERTIES AND VIRUS SAFETY OF A PASTEURIZED ANTITHROMBINIII-CONCENTRATE“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644154.

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The possible occurance of up to now unknown human pathogenic viruses makes it necessary to reconsider thestrategies for the preparation of each plasma protein concentrate used for substitution therapy. Even up to now safe products may be contaminated by infectious particles in the near future. Hence, each procedure for the preparation of such proteins should critically be checked for the elimination of contaminating proteins and should contain an inactivation step for pathogenic agents.Since about 4 decades the pasteurization of albumin in presence of stabilizers has been found to be a safe and mild method to inactivate infectious agents. Using the stabilizersglycine and sucrose, we have now been able to pasteurize antithrombin III without the usual changes in molecular properties.The product is more than 98 % pure and contains only traces of contaminating proteins. The pasteurization does not alter the electrophoretic behavior of the molecule in membrane electrophoresis (ME) and polyacrylamidgel electrophoresis (PAGE). The reactivity with heparin is nearly unchanged as tested by heparin cofactor activity and twodimensional immunoelectrophoresis. No neoantigen formation due to the pasteurization could be detected.Using model viruses the efficacy of the pasteurization step has been tested. The following results have been obtained: HIV ≥106.7 (1), CMV ≥ 104.5 (2), HSV ≥106.8 (4), Poliomyelitis virus ≥106.9 (4); the number in brackets represent the time in hours necessary to totally inactivate the given virus titer.

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Pasi, K. J., und F. G. H. Hill. „NO EVIDENCE OF HEPATITIS OR HIV TRANSMISSION IN VIRGIN HAEMOPHILIC BOYS TREATED WITH BRITISH HEAT TREATED FACTOR VIII CONCENTRATE (8Y)“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643972.

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HIV and hepatitis virus transmission is of major concern with factor VIII therapy. Non-A, non-B hepatitis (NANBH) has a near 100% incidence in patients previously treated with unheated large pool factor VIII concentrates. NHS heated high purity factor VIII concentrate (8Y) undergoes severe protracted heat treatment of the freeze dried concentrate theoretically sufficient to inactivate hepatitis viruses as well as HIV. Infusions of 22 different batches of 8Y have been given to 18 children with haemophilia A (10 virgin patients; 8 who had only received single donor cryoprecipitate) have been treated for up to 18 months. Regular testing for viral antibody seroconversion and biochemical liver enzymes have been made. None had had clinical or biochemical evidence of liver disease prior to the commencement of 8Y therapy. All these boys were immunized with HBVax at the time of the first treatment with 8Y and were HIV antibody negative.Liver function tests were to be performed monthly but due to patient non-compliance this was only achieved in 60% of patients.All patients receiving 8Y have remained anti-HIV seronegative. Only the virgin patients can be considered suitable for evaluation with regard to the transmission of NANBH. These boys by this time have received multiple batches of 8Y (mean 5 batches, range 1 to 14). In only 1 patient has an isolated rise in aspartate transaminase (AST) been noted (AST 27 to 131 IU/1) 6 weeks aftertreatment with a new batch, but no rise in alanine transaminase (ALT) or clinical evidence of liver disease was found. Viral serology was performed. AST returned to normal within 12 days.This batch was received by 3 of the virgin and 2 of the previously cryoprecipitate treated boys. All these 5 boys who were exposed to the suspect batch had normal liver enzyme levels when measured within 4-6 weeks of exposure.Of the 10 virgin patients receiving multiple batches of 8Y a transient rise in AST but with no rise in ALT has only been noted in 1 patient. In the absence of firm biochemical evidence of liver disease NANBH is an unlikely cause. Lack of transaminase rises in other virgin patients strengthens this assunption. We conclude that 8Y reduces the incidence of NANBH and HIV transmission.

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Heimburger, N., P. Fuhge, J. Hilfenhaus, G. Kumpe und H. E. Karges. „EXPERIMENTAL STUDIES CONCERNING THE VIRUS SAFETY OF PASTEURIZED FIBRINOGEN“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644153.

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Fibrinogen is available for substitution in afibrinogenaemic patientssince about 4 decades. However, it soon turned out that those concentrates bear a high risk of transmitting serum hepatitis. Over many years it was not possible to produce safe concentrates of fibrinogen. Hence, the therapy with this protein was limited to vital indications. We have now succeeded to stabilize fibrinogen inaqueous solution for pasteurization over 10 to 20 hours at 60°C.The efficacy of the virus inactivation was tested using various animal viruses. Following results were obtained.Tests in chimpanzees for hepatitis B safety revealed that this procedure inactivates and eliminates 105.2 CID50 of hepatitis B virus; HIV experiments are going on.By immunizing rabbits with the pasteurized fibrinogen and absorption of the antiserum obtained with the unpasteurized product, an exposition of neoantigens during heating in aqueous solution could be excluded. This result could be further confirmed using passive cutaneous anaphylaxis.The coagulability of the pasteurized fibrinogen is unchanged, compared to not pasteurized material. It iseasily soluble and can be used for both, i. v. infusion and as a tissue adhesive. The clinical tolerability is very good.

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