Dear Colleagues,

A few efficacious vaccines against canine leishmaniasis are available, though high protection efficiency is desirable. The search for effective vaccines against pathogens is never easy, and it is especially challenging concerning parasites. Unambiguous determination of the protection of an animals or patients against the parasite requires a better understanding of the immune response to Leishmania spp. Currently, parasite burden determination and clinical sign assessment are the only pivotal parameters for this purpose. Strictly speaking, the Th polarization paradigm is valid for the Leishmania major—mouse infection model, whereas canine and human leishmaniases are characterized by a balanced immune response. Increased parasite burden; Th2 response predominance; IL-10 and TGF-β expression; Leishmania-specific cell immunosuppression; and Leishmania-specific IgG, IgM, IgA and IgE are associated with disease progression. Conversely, increased PBMC levels after leishmanial antigen stimulation, IFN-γ and TNF-α expression, T CD4⁺, CD8⁺ and B cell proliferation, and positive IDR are related to the achievement of protection against the parasite. The role of antigen-presenting cells is pivotal in a successful immune response against Leishmania, stimulating IL-1, IL-6, and IL-12 production. IL-12 triggers the differentiation of immature T cells into Th1 and Th17. Th17 cells may favor protection against human VL via IFN-γ and IL-17 production but may lead to disease progression in the case of human CL. IFN-γ and IgG2a associations with protection and fluctuations over time depending on the host species are debatable. iNOS induction and subsequent NO production associated with the Th1 response is the most remarkable protection mechanism, but certain parasite strains are resistant to NO. A better understanding of the Leishmania evasion mechanisms is still required, including inhibition of NO production, ROS-mediated host cell killing, blocking of antigen presentation and cytokine production, and recruitment of cells secreting IL-10 such as T regulatory cells. In addition to this complexity, vaccine experimentation for leishmaniasis is especially challenging because rodents are not always an appropriate animal model, particularly for VL, and the commercial reagents used are usually scarcer and of lower quality. Therefore, I encourage you to contribute to this Special Issue with a vaccine trial report (either positive or negative), a vaccine trial review, or a specific industrial development or methods paper, to move vaccine research forward. Immune response research papers and reviews are also welcome, particularly those that organize knowledge and improve our understanding of the immune response and parasite evasion mechanisms.

Dr. Pedro José Alcolea
Dr. Ana Alonso
Guest Editors

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• Leishmania
• Vaccines, immune response assessment
• Antigen presentation, lymphoblastic proliferation
• Cytokines, evasion mechanisms
• Nitric oxide resistance
• Antigens, vaccine candidates, and adjuvants
• Parasite burden
• Clinical signs, diagnosis
• Immunoinformatics, genomics
• Therapeutic vaccines, industrial development.