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Research project (§ 26 & § 27)
Duration : 2011-01-01 - 2012-02-21

Different species of Pseudomonas are used as plant protecting agents especially to bate potatoes. To achieve an admission from the authorities the Pseudomonas strains must be tested for their toxicological properties. To circumvent animal studies, test systems are developed to analyse the harmful potential on in vitro cultures of lung epithelial cells. Therefore Calu-3 cells are grown on transwell plates until tight junctions are formed. To classify the bacterial strains, the integrity of the tight junction is evaluated after incubation of Pseudomonas with cell cultures.
Research project (§ 26 & § 27)
Duration : 2009-08-01 - 2012-07-31

Different antibodies against HIV-1 have been developed at the Department of Biotechnology and have been tested in numerous in vitro studies and some of them also in clinical trials. Among others the mAb 4B3 demonstrated promising results in a macrophage assay infected with virus strain BaL and TV1. To test their potency in an in vitro mucosal system, it is necessary to swith the subclass from IgG to IgA specificity. Naturally occurring IgAs pass the epithelial barrier by cellular internalization via endocytosis with subsequent cleavage of the extracellular part of the receptor which remains at the IgA molecule, known as secretory component. This enables to transport the dimeric IgA from the site of application through the tight epithelial layer to the luminal surface. To test the IgA antibodies in an mucosal application the secretory component must be already coexpressed with the antibody. Therefore, this challenging project needs the expression of a heteropolymeric complex consisting of two antibody specific light and heavy chains connected by the common J-chain and associated with the secretory component. Afterwards the antibodies must be purified and, characterized and tested in different model systems.
Research project (§ 26 & § 27)
Duration : 2008-05-01 - 2012-09-30

Targeting the humoral and cellular immune response by modulation of an anti-idiotypic antibody mimicking HIV-1 gp41 Internal image antibodies are a subclass of anti-idiotypic antibodies, which recognise the antigen-binding site of first generation antibodies comprising a replica of the epitope and are thus able to mimic the original antigen (antigenic site) functionally or even structurally. Based on this mechanism an anti-idiotypic antibody, termed Ab2/3H6 was developed against a promising human monoclonal antibody 2F5, which is able to neutralise a number of primary HIV-1 isolates. Since the development of 2F5-like antibodies has failed so far and the expression and passive administration of monoclonal antibodies (mAb) in general, is very expensive the demand for an active immunisation is still required. Ab2/3H6 is one of these potential vaccines candidates, which could be easily administered to HIV-1 infected patients as well as to healthy individuals. In the context of this FWF project the chimeric Ab2/3H6 will be completely humanized to (1) reduce the unspecific human anti mouse antibody (HAMA) response and to (2) improve the specific immune response directed against the antigen binding site of Ab2/3H6. Additionally we will focus on the cellular immune response since this type of immune reaction also plays a key role in the development of an active vaccine against HIV-1. This will be arranged out by a novel human Ab2/3H6/interleukin-15 fusion protein which will be further investigated in vitro and finally in vivo. We will also analyse the use of a specific tetanus toxin sequence that should enhance the specific immunogenicity of Ab2/3H6 by adding a tag to the antitdiotypic antibody. The in vivo studies will be performed in a rabbit animal model since this species is able to produce long complementarity determining regions sufficient for a 2F5-like immune response comparable to humans. Finally we will establish a co-crystallisation of 2F5 and Ab2/3H6 to disclose the secret of the remaining contact residues of mAb 2F5 which are essential for advanced vaccine design.

Supervised Theses and Dissertations