Capsid Like Particles as Vaccine Vectors – CALIPSO

The constant need for immunization to prevent life-threatening diseases worldwide is urging the search for new vaccines. Progress in the development of modular virus-like particles for antigen (Ag) delivery is currently impaired by difficulties in the grafting of large Ag. We recently established a novel Ag delivery vector assembly based on molecular recognition between recombinant bacteriophage T5 Capsid-Like-Particles (CLP) and T5 capsid decoration protein pb10. We harnessed the modularity of pb10 to design pb10-Ag chimera that anchor with strong affinity onto the CLP surface. This highly efficient chemical-free grafting system yields CLP able to irreversibly display a regular array of large Ag. Immunization assays in mice with the model Ag ovalbumin have shown that CLP constitute highly immunogenic and auto-adjuvant Ag nano-carriers with great prospects for vaccination. CALIPSO proposes to advance this new type of vaccine vector to address public health issues, for prophylactic or therapeutic usage. We will leverage the potential of T5 CLP-Ag to elicit potent immune responses towards Rotavirus (RV) and Human Papilloma Virus (HPV), two health-threatening pathogens requiring new types of vaccines. We will design tailored CLP carrying either RV surface Ag or tumor Ags from oncogenic HPV and characterize whether the humoral or cellular immune responses they elicit in mice achieve protective immunity against RV or control the growth of HPV-induced tumors. As supporting technology to CLP-Ag development, we will devise a panel of nano-bio-analytical approaches for rapid and efficient assessment of CLP integrity and Ag grafting efficiency, key requirements for regulatory approval. The CALIPSO consortium of experts in phage T5 assembly, immunology and nano-characterization methodologies aims at achieving structurally stable, safe and effective Ag-grafted CLP to develop breakthrough technology for faster vaccine development and implementation.