Uma Nova Vacina de Quarta Geração Contra Leishmaniose Canina

Defining the preferred and minimal characteristics of an innovative highly efficient fourth-generation prophylactic anti-leishmanial vaccine, we propose the development of a vaccine, an mRNA construct expressing leishmanial MAPK10 antigen and IL-7 from a self-inactivating, non-integrating novel lentiviral vector, offering a new paradigm for vaccine development against neglected tropical diseases. Our data indicate that the L. major antigen- LmjMAPK10- administered as protein, DNA or mRNA, protected susceptible BALB/c mice against both cutaneous and visceral infection indicating successful coverage of the required breadth5,6. IL-7 functions as a natural adjuvant potentiating LmjMAPK10-induced anti-leishmanial antigen-specific host-protective memory T cell response in a susceptible host (7 and supporting figure 1-2). The project covers the preclinical process development phase covering safety, immunogenicity, and protection against challenge infection trials in mice models. This will be followed by clinical studies in an ex vivo T cell activation assay with CanL patients’ cells and pilot clinical trials (POC veterinary studies) in genetically distinct canine populations following the Good Clinical Practice8 to support future veterinary product registration. Thus, the project will create the conditions to advance in the vaccine development pipeline to confirmatory TASS and TAES. Therefore, we aim to: [1] Design a novel lentiviral recombinant vector for expressing an RNA coding for a leishmanial antigen (MAPK10) and interleukin-7 as a natural adjuvant; [2] Evaluate the stabilized memory T cells' phenotype and function, setting a novel benchmark for understanding the mechanistic foundation of the vaccine. Experimentally confirm the immunogenicity, tolerance, and safety of the vaccine construct: [3] Demonstrate the prophylactic efficacy against L. infantum in experimental infection; [4] Test the proposed vaccine as a combination therapeutic vaccine with amphotericin B, miltefosine, or ketoconazole + metronidazole chemotherapies to enhance long-lasting immunity but minimize drug-induced resistance and side effects; [5] Conduct proof-of-concept veterinary clinical studies in the target species (dogs). In conclusion, this ambitious but feasible project is poised to significantly advance the field of veterinary vaccine development against Leishmaniasis. By focusing on the innovative use of the LmjMAPK10 antigen in combination with IL-7 as a natural adjuvant, we aim to develop the first fourth-generation vaccine that is both safe and effective. Our comprehensive approach aims to reduce the incidence of CanL, directly benefiting dogs and indirectly reducing zoonotic risks to humans. By encompassing rigorous safety assessments and moving towards pilot clinical trials in dogs, our project enhances global health. Integrating this vaccine with current treatments, we aim to boost immunity, minimize side effects, and combat drug resistance, marking a significant advancement in veterinary healthcare. Our project tackles CanL's immediate challenges and establishes a scalable vaccine platform for various infectious diseases, contributing to sustainable veterinary public health and paving the way for more efficient and innovative veterinary care.