Induction of a MHC class I-restricted, CD8 positive cytolytic T-cell response by chimeric HIV-1 virus-like particles in vivo: implications on HIV vaccine development

Abstract

New insights into HIV-pathogenesis suggest that the cell mediated immune response might play a crucial role in controlling HIV infection by suppressing HIV-replication in CD4-positive cells by a lymphokine-like soluble factor and by killing HIV-infected cells via classical CTL mediated lysis. This type of a cellular immune response rather than an antibody response seems to be most promising to protect if not from infection, so at least from disease. Therefore rationally designed candidate vaccines should be capable of inducing a cell mediated immunity in addition to a humoral immune response. In order to avoid adverse side effects upon immunization, carefully selected antigens and epitopes should be presented in a favourable manner to the immune system. In previous experiments, we could demonstrate that the gag-polyprotein precursor, known to include a series of T-helper and CTL epitopes, assembles to highly immunogenic, complete noninfectious HIV-1 virus-like particles (VLP). Based on these VLP we developed a novel antigen presentation system, which allows the presentation of selected epitopes derived from HIV reading frames other than gag to the immune system. Alternatively complete derivatives of the HIV-1 external glycoprotein can be presented by the VLP. Immunological analysis of different VLP preparations in a BALB/c mouse model revealed the induction of a strong CTL response. The significance of these observations for future vaccine strategies is discussed.