Development of a peptide-based therapeutic vaccine to combat HIV disease (chronic immune stimulation)

This project aims to develop a novel therapeutic vaccine that induces nonneutralising antibodies to human immunodeficiency virus (HIV) to modulate disease rather than inhibit infection. Much evidence has now accumulated supporting the concept that acquire d immunodeficiency syndrome (AIDS) is an immunological disease induced by HIV-1 rather than simply the virus depleting CD4+ T-lymphocytes. It is therefore also important to develop immune-based strategies that target the chronic immune stimulation induced by HIV. Previous research has shown that sustained antibody responses a region of the HIV envelope glycoprotein (gp120) called C5 is associated with lower immune activation/slower disease progression. Indeed, loss of anti-C5 antibodies leads to accelerat ed disease progression. Long term non-progressors (LTNP) represent approximately 5% of HIV-infected individuals and have sustained antibody responses to the C5 domain. They can live in the absence of antiretroviral therapy (ART) for many years despite hav ing circulating virus. This project involves a consortium of 4 partners. Bionor Immuno will design peptides that will be tested in small animal models for immunogenicity at the Norwegian Institute of Public Health. Bionor Laboratories will develop an ELIS A assay kit to test for the presence of anti-C5 antibodies, a test that can later be commercialised with the C5 therapeutic vaccine. Toxicological analyses and regulatory affairs will be outsourced. St. Georges University of London UK will prepare for and put in place the assay systems needed for a phase I/II clinical trial. The C5 therapeutic vaccine may be used alone or in combination with other therapeutic vaccines to enhance the safety of ART-free periods or delay the need for ART. It may also be used for patients on continuous ART to alleviate chronic immune stimulation that can persist despite suppression of virus to undetectable levels.