Leishmania infantum antigenic proteins in vaccine formulations: a systematic review in murine models of visceral leishmaniasis

Abstract Visceral leishmaniasis (VL) is a neglected and often fatal parasitic disease caused by protozoa of the Leishmania donovani complex and transmitted by sandflies. With approximately 300,000 new cases annually, the disease remains a significant public health challenge, further aggravated by the limited effectiveness of available therapies, making vaccine development a strategic necessity. Advances in genomics and molecular biology have enabled the rational selection of promising antigens, particularly recombinant proteins, which have demonstrated the ability to induce protective immune responses in experimental studies and show translational potential for clinical applications in both humans and dogs. This systematic review aimed to gather and critically analyze preclinical evidence on the efficacy of Leishmania infantum recombinant proteins used as immunogens in VL vaccine formulations in murine models. The protocol followed PRISMA recommendations, with studies identified through structured searches in the Medline, Scopus, and Web of Science databases. In total, 37 studies met the inclusion criteria. Antigenic composition, stage of expression during the parasite life cycle, experimental design, infection and treatment approaches, immune response characteristics, and parasite load outcomes were evaluated. Most studies used proteins derived from amastigote or promastigote forms, generally administered as isolated antigens. The predominant immunization regimen consisted of three doses given at 15-day intervals, most commonly using 25 µg delivered subcutaneously. The vaccine formulations predominantly induced Th1-type immune responses, characterized by increased levels of IFN-γ, GM-CSF, IL-2, IL-12, and TNF, cytokines essential for macrophage activation and parasite control. Significant reductions in parasite burden were observed mainly in the spleen, liver, bone marrow, and lymph nodes. Based on the preclinical evidence analyzed, the results reinforce that recombinant proteins exhibit high immunogenic potential and protective capacity, highlighting them as promising candidates for immunoprophylaxis against L. infantum and as a strategic approach for the development of more effective vaccines against visceral leishmaniasis.