Targeting the humoral and cellular immune response by modulation of an anti-idiotypic antibody mimicking HIV-1 gp41
Abstract
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.
antiidiotypic antibody HIV-1 Interleukin-15 Humanization
Publikationen
Influence of different genetic parameters and regulatory sequences on recombinant expression of a monoclonal antibody
Autoren: Renate Kunert, H. Reisinger, W. Steinfellner, B. Stern, H. Katinger Jahr: 2008
Journal articles
Humanization strategies for an anti-idiotypic antibody mimicking HIV-1 gp41.
Autoren: Mader, A; Kunert, R; Jahr: 2010
Journal articles
Project staff
Renate Kunert
Univ.Prof. Dipl.-Ing. Dr.nat.techn. Renate Kunert
renate.kunert@boku.ac.at
Tel: +43 1 47654-79852
BOKU Project Leader
01.05.2008 - 30.09.2012