Currently about 34 million are infected worldwide by the Human Immunodeficiency Virus (HIV). Although great efforts in the field of highly active antiretroviral therapy (HAART) and especially the introduction of antiviral drugs into countries mostly affected by the epidemic point at a reduction of newly acquired infections and HIV associated mortality, still about 1700 persons are newly infected by HIV-1 every day. Furthermore, side effects of HAART, viral reservoirs in the body not accessible to the drugs and the tremendous costs caused by the need for lifelong treatment, require the development of new therapeutic and prophylactic strategies against HIV-1.
Understanding the natural mechanisms of virus control acting in a minority of individuals infected with HIV that are able to naturally control the infection without HAART over many years, could help to elucidate the protective mechanisms and potentially allow to develop new drugs and therapeutic/prophylactic vaccines. We are particularly interested to study virus neutralizing antibodies as well as their epitopes from such chronically infected persons with a rather healthy immune system. In collaboration with our clinical partners, we analyze “HIV controllers” for the presence of virus neutralizing antibodies in their plasma by in vitro neutralization assays. We then identify these antibodies based on the phage display technology or on single B cell sorting with appropriate HIV-1 envelope (Env) constructs. We generate various soluble trimeric HIV-1 Env proteins that serve as targets for the selection of antibodies derived from the HIV controllers, as immunogens for the generation of neutralizing antibodies or for structural analysis. The selected neutralizing antibodies are further analyzed for their neutralizating capacity in vitro against a panel of different HIV-1 strains.
Further antiviral strategies involve the selection of peptides/antibodies interfering with specific steps during virus replication, with a particular focus on inhibition of virus entry into target cells.
HIV-1 mainly infects CD4-positive T cells and macrophages, although infection of additional cells in different organs may contribute to viral reservoirs in the body. Here we are interested to further elucidate the infectibility of primitive human stem cells (HSC) and multipotent progenitors (MPP). Starting from HSC/MPP from human cord blood or primary patient material we analyze their infectibility by HIV-1 based on multicolour FACS analysis, colony assays and qPCR.
Dr. Ursula Dietrich performs as Guest Editor of the Vaccines Special Issue “Advances in Antibody-based HIV-1 Vaccine Development”.