Research Project
6800114
DESCRIPTION (provided by applicant): The human immunodeficiency virus type 1 (HIV-1) pandemic now eclipses all other known epidemics in terms of its impact on human morbidity and mortality, as well as the global economy. The need for an efficacous and cost effective vaccine is urgent, but has proven to be an enormous scientific challenge. Ideally, an HIV-1 vaccine will induce sterilizing immunity against infection with a broad range of virus variants. There have been some notable advances in development of vaccine regiments that are able to generate significant levels of protection against development of AIDS in non-human primate models. These vaccines allow animals to control viral challenge by strong priming of virus-specific cytotoxic T cells, but this cannot prevent infection and mechanisms to induce neutralizing antibodies remains a vital goal. Recombinant virus-like particles show great promise for development of potent immunogens that are able to induce high levels of antibody production. Large Scale Biology Corporation has developed a virus-like particle antigen display system based on rod-shaped plant viruses. Linear epitopes that represent the binding site of HIV-1 neutralizing antibodies, and HIV-1 surface glycoprotein loop structures will be displayed in ordered, repetitive, quasicrystalline arrays on the surface of rod-shaped tobacco mosaic virus and potexviruses, and are expected to induce high levels of peptide-specific antibodies. Methods to enhance the expression and purification of recombinant viruses displaying HIV-1 peptides will be employed. The recombinant viruses will be characterized by biophysical, chemical and immunological methods. Recombinant viruses that appear promising will be used to immunize guinea pigs, and guinea pig sera will be used to assay for HIV-1 neutralizing activity in vitro. Demonstration of neutralizing activity will justify future work on development of plant virus peptide display systems for HIV-1 subunit vaccines. This system is very easy to scale up, and allows production of extremely cheap, effective vaccines.
