Virus-like particle endocytosis pathways and presentation of captured antigens

Abstract

The proteins of many viruses can be assembled into strictly organized structures virus-like particles bearing antigens of the original viruses and may also be artificially decorated with antigens of other pathogens. These particles contain no viral genome and lack infectivity but can be highly immunogenic and therefore being actively used for vaccine development. Undoubtedly, while designing vaccines, it is necessary to take into account information about the interaction of vaccine components with immune system particularly antigen-presenting cells. This is especially important for virus-like particles because, like other nanometer-sized particles, they can enter antigen-presenting cells using various endocytosis pathways. The latter exploit multiple receptors, generate endocytic vesicles of different sizes, and, most importantly, are associated with varying fates of captured material. Here we review the mechanisms of phagocytosis, macropinocytosis, clathrin-mediated endocytosis, rapid endophilin-mediated endocytosis, and several endocytic pathways associated with lipid rafts. The data are presented on the relationship between various endocytic pathways and sorting of absorbed cargo in early endosomes as well as enzymatic degradation of the late endosomes contents. We also describe the mechanisms of distribution of absorbed antigens within antigen-presenting cells to be loaded onto the class I and II major histocompatibility complex molecules. The data are presented on the endocytosis of various viruses during cell infection, as well as a comparative analysis of the endocytosis pathways for virus-like particles and related viruses. It has been noted that virus-like particles, along with the absorption pathway specific for parent virus, can rely on additional endocytic pathways to be also artificially targeted at the selected endocytic receptor and relevant absorption pathway. It allows to select or design particles with optimal endocytosis and antigen presentation to induce a protective immune response upon vaccination. It should be assumed that most prophylactic vaccines require particles that are well engulfed by antigen presenting cells and direct material to endolysosomal degradation, or particles whose uptake directs material to both late and static early endosomes, making antigens available for direct and cross presentations. Finally, we discuss virus-like particles for the delivery of drugs or genetically engineered constructs, as well as optimal endocytic pathways that should protect the payload of these particles from endolysosomal degradation.