Design and immunogenicity assessment of HIV-1 virus-like particles as a candidate vaccine

Zhang, XiZhen; Wang, XiaoDan; Zhao, DongHai; Meng, XiangYu; Zhao, XingHong; Yu, XiangHui; Kong, Wei

The major advantage of a VLPs approach compared to live-attenuated virus is that VLPs express multiple viral epitopes that stimulate a diverse set of immune responses, without many of the deleterious effects of a live-attenuated virus. VLPs have the potential for activating both endogenous and exogenous antigen processing pathways, leading to presentation of viral peptides by MHC class I and class II molecules. These multi-epitope vaccines are more likely than their single component counterparts to generate a broad-based immune response capable of clearing HIV-1 immune evasion mutants. VLPs may be more cost efficient than co-inoculating multiple single gene vaccines for future Phase I clinical trials. Another advantage of VLPs compared to single recombinant protein vaccines is the ability of VLPs to bind and enter cells expressing appropriate receptors. HIV-1 VLPs are able to bind to CD4 and chemokine receptors via gp120, and to enter into professional antigen presenting cells such as macrophages and dendritic cells (both cell types express CD4 and CCR5). After infection, viral proteins can be processed and presented on MHC class I molecules, therefore promoting presentation to T cells by APCs. In addition, cell-free VLPs bound with antibodies can be taken up by phagocytic cells via Fc receptors, thus increasing MHC class II presentation. VLPs have been expressed in Baculovirus expression systems [25] and Saccharomyces cerevisiae [26, 27] . These systems produce large amounts of particles from eukaryotic cells. However, they are usually limited to expressing only one gene, and therefore are not easily used to produce multigene VLPs. In addition, in order for particles to bud from yeast, the outer membrane needs to be removed.