Martins, A.Z., et al. Advances in recombinant protein vaccines against Leishmania infantum: a systematic review of vaccinal constructs and delivery strategies. Acta Trop, 2025 Oct, 270:107796.

Martins, A.Z., et al. Advances in recombinant protein vaccines against Leishmania infantum: a systematic review of vaccinal constructs and delivery strategies. Acta Trop, 2025 Oct, 270:107796. PMID: 40840696

• This systematic review addresses the ongoing global health challenge posed by leishmaniasis, a neglected tropical disease caused by Leishmania infantum, with visceral leishmaniasis being particularly severe and potentially fatal if untreated. Despite advances in vaccine development, no licensed human vaccine currently exists, underscoring the urgent need for effective immunization strategies. Recombinant protein vaccines have emerged as promising candidates due to their ability to elicit targeted immune responses. The primary goal of this work is to systematically evaluate the current state of recombinant protein vaccine research against L. infantum in BALB/c mice, focusing on vaccine formulations, delivery strategies, and immunological outcomes, thereby identifying gaps and guiding future efforts toward the development of effective vaccines for the control of visceral leishmaniasis.
• The paper highlights the significant role of adjuvants such as saponins and QS-21 in enhancing the immunogenicity of recombinant protein vaccines against L. infantum. Saponins, including extracts like Quillaja saponaria, are known to stimulate robust cellular and humoral immune responses by forming immune-stimulating complexes that promote antibody production and activate cytotoxic T lymphocytes. QS-21, a purified saponin fraction, specifically induces Th1-type cytokines like IFN-γ, complementing other adjuvants to drive a protective immune profile. These adjuvants function by engaging immune pathways that favor cellular immunity essential for controlling intracellular parasites like Leishmania spp.
• The conclusions of the paper emphasize that adjuvants such as saponins and MPLA play a crucial role in eliciting a protective Th1 immune response against Leishmania infantum by promoting cellular immunity. The integration of advanced delivery systems, including nanoparticles, liposomes, and polymer-based formulations, can further enhance antigen stability, biodistribution, and immunogenicity. However, despite these advances, no formulation has achieved complete parasite clearance, highlighting ongoing challenges in vaccine efficacy. The authors advocate for future research to focus on optimizing adjuvant combinations, discovering novel antigens, and developing innovative delivery platforms to improve the effectiveness and durability of recombinant protein vaccines. They also acknowledge current methodological limitations and the necessity for standardization to facilitate translation into clinical practice.

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