Engineered enveloped VLPs with high-density antigen coatingApplication to Feline leukemia virus

Zusammenfassung

Retroviruses are infectious agents that have been identified in many species, causing diseases of major importance. Such is the case of the Human immunodeficiency virus (HIV-1), which is the causative agent of the acquired immunodeficiency syndrome (AIDS). Unfortunately, despite large efforts, the development of a protective vaccine against HIV has proven elusive for more than 40 years. Not only humans are the target of this family of viruses, but a wide range of animals can also be infected by them. For instance, cats are infected with different retroviruses, one of the most common pathogens being the Feline leukemia virus (FeLV). Near 60 years after the discovery of FeLV, none of the available commercial vaccines provide full protection from infection. Therefore, retroviruses can dramatically impact human and animal health, but vaccines have the potential to save millions of lives and change history. Efforts to improve current vaccines and design new strategies are one hot topic in medical research. This work particularly focuses on Virus-like particles (VLPs), a vaccine platform which mimics the structure of a virus, lacking the viral genome and thus, being non-infectious. Recently, our group developed a modified VLP platform based on the HIV structural protein Gag. These VLPs show a high density of immunogen on their surface and induce a potent and functional immune response in mice even in absence of adjuvants and at a low VLP dose. The objective of the present work is to analyze the versatility of our HIV-based VLP platform and its adaptability to another retrovirus. Specifically, this thesis focuses on FeLV. First, we produced and optimized FeLV-Gag based VLPs. Then, we loaded on the surface of FeLV-based VLPs different antigens derived from the viral Envelope glycoprotein. Finally, immunogenicity was tested in two different murine animal models, in which we analyzed different delivery systems (purified VLPs or nucleic acid) and studied the impact of adjuvants in the purified VLPs delivery system. Altogether, this thesis not only confirms the versatility of the HIV-1 Gag-based VLP vaccine platform but also presents retroviral VLPs as an excellent alternative to more conventional vaccines. Moreover, this work sheds light on FeLV vaccine research, considering that FeLV is not only of interest to veterinary practice but also could be a relevant model to help understand HIV-1 immunology.