Development of an anti-idiotypic HIV-vaccine

The development of a vaccine against HIV is one of the biggest concerns of today`s health care policy. Common agreement exists that the spread of HIV in underdeveloped countries is the main challenge. Combination therapies with antiretroviral drugs improved the treatment of AIDS during the last years. In case of children this highly activated antiretroviral therapy causes severe side effects, since their immune system has not developed completely and also organs can be damaged. In contrast, neutralising antibodies are immunoglobulins generated by the immune system in course of bacterial and viral infections and combat the invading agents. In case of HIV, neutralising antibodies are predominantly directed against variable domains and such the virus is able to evade the immune system through its high mutational rate. At the Institute of Applied Microbiology we have developed human anti HIV-1 monoclonal antibodies (mAb) capable of preventing cells from viral infections and neutralising all viral isolates tested so far either alone or in combination of our antibodies. The antibodies showed very promising results in different animal models so that a phase I clinical trial was performed with great success. With this information in mind we intended a concept of active immunisation against AIDS since passive immunotherapy is of operating expense. Anti-idiotypic antibodies are directed against the antigen binding domain of an antibody and are able to display the structure of the antigen. Therefore, the concept of vaccination with an anti-idiotypic antibody against the neutralising mAb 2F5 and such mimicking a highly conserved epitope was actualised with the establishment of the anti-idiotypic antibody Ab2-3H6. This murine antibody was developed at our institute in a previous FWF project: Ab2-3H6 is able to induce a humoral immune response with HIV-neutralising titres in the animal model confirming the therapeutic potential. Further development of this antibody requires switching the mouse antibody to a chimeric human/mouse molecule to prevent the generation of human anti-mouse antibodies (HAMAS) in men. Since the specificity and efficacy of the murine Ab2-3H6 was affirmed in mice the goal of this project is to humanise the antibody and to prove specificity properties for the recombinant protein. We will establish a recombinant cell line expressing the chimeric antibody and provide enough purified material to go into further macaque models to prepare the antibody for a human application.