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  • 1
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To reduce the opportunities for human immunodeficiency virus type 1 (HIV-1) to evade vaccine induced immunity, the development of subunit vaccines must focus on the characterization of immunogenic epitopes, which are major targets for the immune system. The most dominant site for elicitation of neutralising immune response is located on the external envelope glycoprotein gp 120 within the third variable domain (V3). To overcome virus type specificity of antibodies directed to the V3-domain we designed a 36 amino acids long gp 120/V3-consensus peptide (V3-C36) based on published biological data and sequence comparisons of various HIV-1 virus isolates. This peptide contains a conserved core sequence which is suggested to form a surface-exposed β-turn. This peptide also includes T-cell epitopes defined in mice and humans, an ADCC-epitope and two highly conserved cysteine residues which were oxidized to form a cystine derivate, thus allowing correct peptide folding. In ELISA-tests, this peptide reacts with at least 90% of randomly selected sera of European and African patients infected with HIV-1 and is recognized by three different HIV-1/V3 “type-specific” antisera (MN, RF, IIIB-strain). Using this peptide as immunogen in rabbits, antisera could be raised with highly cross-reactive and HIV-1/IIIB strain neutralizing properties. Moreover, HTLV/HIV-1/IIIB specific cytotoxic T-lymphocytes (CTLs) of BALB/c mice infected with a gp 120 recombinant vaccinia virus recognized the central 16- and 12-mer peptides of the V3-C36 consensus peptide in cytolytic assays, indicating perfect compatibility of the consensus peptide with the IIIB-primed CTLs. The DNA-sequence encoding the V3-consensus loop region might be an important component in newly designed recombinant subunit vaccines. In addition, due to its broad serological reactivity, the V3-consensus peptide might play an important role in special diagnostic purposes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV-1 group specific core antigen p 55gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia-and baculoviruses were established encoding the entire core protein p 55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p 55gag was expressed in combination with the protease (p 55-PR) or with the entire polymerase (p 55-pol), respectively. Budding of 100–160 nm p 55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p 55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection ofSpodoptera frugiperda (Sf9) insect cells with the recombinantAutographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2-terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p 55-PR gene construct by recombinant baculovirus resulted in complete processing of the p 55gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p 55, both inEscherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p 55 resembling that of HIV infected H 9 cells could also be achieved in the vaccinia system by fusing the entirepol gene to thegag gene. Moreover, processing was not found to be dependent on amino-terminal myristylation of thegag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p 55 into p 24, p 17, p 9 and p 6 abolished particle formation. Purified immature HIV-virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p 55gag particles represent a noninfectious and attractive candidate for a basic vaccine component.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The CD4 cell surface antigen belongs to the immunoglobulin superfamily and is the primary receptor for the human immunodeficiency virus 1 (HIV-1). The high affinity interaction between HIV-1 and CD4 is mediated by the viral envelope glycoprotein gp120. Recombinant soluble CD4 (rsCD4) has been shown in vitro to be an effective inhibitor of HIV-1 and HIV-2 propagation in lymphoid cells. A variety of antibody-like molecules were constructed, consisting of different parts of the extracellular domain of CD4 fused to immunoglobulin constant regions. The fusion proteins were expressed in mammalian cell lines and purified via affinity chromatography. The specificity and anti-viral effects of the different CD4-immunoglobulin constructs against HIV were analysed by different immunological tests, i.e., immunofluorescence, neutralisation and in vitro assays. In pharmacokinetic studies, differences were found in serum half-life between the four- and two-domain CD4 constructs in cynomolgus monkeys and between glycosylated and deglycosylated CD4-Fc constructs in rabbits. In two in vivo experiments using the four-domain CD4-Fc in SIV-infected macaques, no beneficial effects were observed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 42 (1999), S. 389-401 
    ISSN: 1437-1588
    Keywords: SchlüsselwörterVirusbedingte hämorrhagische Fieber (Ebola Marburg ; Lassa ; Krim-Kongo) ; Pest ; Seuchenhygiene ; Quarantäne ; Internationale Gesundheitsvorschriften ; Reisemedizin ; Tropenkrankheiten ; Emerging diseases ; öffentlicher Gesundheitsdienst ; Zivilmilitärische Zusammenarbeit ; Key words Viral Haemorrhagic Fevers (Ebola-Marburg Viral Diseases ; Lassa Fever ; Crimean-Congo Haemorrhagic Fever) ; Pneumonic Plague ; Control of Epidemics ; Quarantine ; International Health Regulations ; Travelling Medicine ; Tropical Diseases ; Emerging Diseases ; Public Health (Services) ; Civilian-Military Co-operation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary At present, the importation into Germany of life-threatening and highly contagious diseases such as pneumonic plague and Ebola is unlikely, but cannot be ruled out. In spite of the extreme rarity of these diseases, guidelines are necessary to prevent the spread of these agents in case of their importation. In Germany, marked regional differences exist with respect to the development of emergency regulations and the availability of specialized centers for diagnostics and therapy. A federal framework is missing. A concept is presented here in which the capacity to respond is substantially augmented with limited additional cost through inter-regional cooperation using existing infrastructure and federally standardized procedures.
    Notes: Zusammenfassung Ein Einschleppen lebensbedrohender und zugleich hochkontagiöser Infektionskrankheiten wie Lungenpest oder Ebola-Fieber nach Deutschland erscheint zur Zeit nicht sehr wahrscheinlich, ist aber grundsätzlich nicht auszuschließen. Gerade wegen der Seltenheit des Auftretens einer solchen Erkrankung sind jedoch auch hierzulande Handlungsrichtlinien notwendig, um gegebenenfalls einer Verbreitung entgegenzuwirken. Die Entwicklung konkreter Schutzvorkehrungen und Handlungsalgorithmen sowie das Vorhalten geeigneter Diagnostik- und Behandlungseinrichtungen ist in den einzelnen Regionen Deutschlands sehr unterschiedlich ausgeprägt. Ein bundesweiter Rahmenplan fehlt. Der vorliegende Konzeptentwurf zeigt, wie die Vorsorge mit vertretbarem finanziellen Mehraufwand durch eine gemeinsame überregionale Nutzung der z. T. vorhandenen Infrastruktur und durch eine Vereinbarung bundeseinheitlicher Vorgehensweisen wesentlich verbessert werden kann.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1437-1588
    Keywords: Schlüsselwörter Tropenkrankheiten ; Virale hämorrhagische Fieber ; Lassa-Fieber ; Infektionsschutz ; Quarantäne ; BSL4 ; Seuchenhygiene ; Öffentliches Gesundheitswesen ; Rettungswesen ; Krankentransport ; Krankenpflege ; Schutzkleidung ; Kontaktpersonen ; Keywords Tropical Diseases ; Viral Haemorrhagic Fever ; Lassa-Fever ; Epidemic Control ; Preparedness Plans ; Quarantine ; BSL4 ; Patient Isolation ; Barrier Nursing ; Protective Equipment ; Contact Tracing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Patients infected with viral haemorrhagic fevers (VHF), pneumonic plague or zoonotic orthopoxvirus infections usually require intensive care and a special isolation. Contact persons must be traced and monitored. Last year our working group published a concept for the management and control of these life-threatening highly contagious diseases. Now the principles of our plan have been accepted. The development of guidelines for rapid reaction to those communicable diseases is an important task for all EU Member States. In Germany microbiological diagnosis is performed by a diagnostic centre (Biosafety-Level BSL4) and supported by a corresponding confirmation laboratory. At present four high security infectious disease units for patient care (HSIU) are available in Munich, Leipzig, Hamburg and Berlin. Another one located in Frankfurt will be functional by 2001. In addition to the HSIU a corresponding number of centres of competence shall be established in order to support and advise the hospitals initially treating the patients as well as the local public health officer. The risk categorisation for contact persons, which has been developed by our working group, has proved to be very useful in practice. Ambulances should be used for transfer of patients to the HSIU. So-called transport-isolators are not suitable for patients who are seriously ill. Air-based transport without using an isolator is a problem, since no decontamination procedure exists. As soon as the last HSIU in the Rhine Main area is working the centres of competence will be established. This will provide competent health care for VHF-patients and a convincing management for these kinds of threats to public health everywhere in Germany.
    Notes: Zusammenfassung Verschiedene virusbedingte hämorrhagische Fieber (VHF), Pocken (humane Affenpocken) sowie Lungenpest erfordern besondere Maßnahmen zum Schutz des Krankenhauspersonals und anderer Personen vor Ansteckung. Kontaktpersonen müssen ermittelt und überwacht werden, um eine Ausbreitung zu verhindern. Ein im Mai 1999 veröffentlichtes Konzept zum Management und zur Kontrolle dieser lebensbedrohenden hochkontagiösen Infektionskrankheiten wurde inzwischen mit Fachöffentlichkeit und Gesundheitsbehörden diskutiert. Bei den zwischenzeitlich aufgetretenen Fällen bestätigte sich das vorgeschlagene Vorgehen : In Deutschland werden die mikrobiologische Diagnostik und Differentialdiagnostik zentral von einem Zentrum der biologischen Sicherheitsstufe BSL4 und einem entsprechenden Bestätigungslabor vorgenommen. Für Isolierung und klinische Behandlung der Patienten stehen vier Behandlungszentren zur Verfügung, ein fünftes soll im nächsten Jahr betriebsbereit sein. Die zunehmende Inanspruchnahme zeigt, dass sich die vorgesehene Schwerpunktversorgung durchsetzt. Handelsübliche Transportisolatoren sind für schwer kranke Personen nicht geeignet. Ohne deren Verwendung können Luftfahrzeuge jedoch nicht regelrecht dekontaminiert werden. Transporte sollen daher grundsätzlich auf dem Landweg erfolgen. Zur Unterstützung und Beratung der erstversorgenden Krankenhäuser und der örtlich zuständigen Amtsärzte sollen um die Behandlungszentren sog. Kompetenzzentren entstehen. Der Personal- und Platzbedarf bei der Versorgung eines an einem VHF Erkrankten in fortgeschrittenem Stadium ist höher als erwartet. Die adäquate Versorgung von Kranken in sog. Bettisolatoren ist nicht möglich. Routinelaboruntersuchungen müssen in der Behandlungseinheit erfolgen. Maßnahmen zur Verhinderung der Weiterverbreitung müssen stärker koordiniert werden. Die von uns vorgeschlagene Einteilung der Kontaktpersonen wird um eine Auflistung der empfohlenen Maßnahmen ergänzt.
    Type of Medium: Electronic Resource
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