Evaluating Lactococcus lactis as a novel antiparasitic vaccine delivery platform: A scoping review of immunization routes and immunological outcomes

Lactococcus lactis has emerged as a versatile bacterial host for antigen delivery in vaccines against parasitic infections. This scoping review aimed to summarize preclinical studies employing L. lactis to deliver protozoan and helminth antigens, focusing on immune responses and protective efficacy. Comprehensive searches were conducted in electronic databases, including Medline/PubMed, Embase, Web of Science, Scopus, ScienceDirect, and LILACS. Eleven studies meeting eligibility criteria were included, encompassing diverse animal models, administration routes, doses, and immunization schedules. Among protozoa-targeting studies, Leishmania and Plasmodium species were most frequently investigated, whereas Giardia was less commonly studied. Reported antigens included LACK, PpSP15, Hsp65, MSP1, MSA2, A2, and CWP2. Vaccination elicited robust Th1-biased responses, with serum IgG (IgG1 and IgG2a) detected in 8/11 studies and secretory IgA in 5/11. Cellular responses commonly included increased IFN-γ, along with modulation of IL-2, IL-4, IL-10, IL-12, and IL-17, and expansion of regulatory T cells. Protective effects ranged from 40 to 71% reductions in parasitic load or cyst shedding, decreased lesion size or paw swelling, to improved survival or reduced parasitemia. In helminths, including Taenia solium and Echinococcus granulosus antigens (TSOL18 and EG95), oral L. lactis-based vaccines induced antigen-specific IgG and IgG subclasses, as well as cellular responses (IFN-γ, IL-4, IL-10), demonstrating efficacy in reducing parasite burden. Taken together, these findings highlight L. lactis as a flexible platform capable of inducing both systemic and mucosal immunity. The immunization route critically shapes the immune profile and protection, emphasizing the need to tailor vaccine strategies to pathogen type, infection site, and desired immune outcome. This review provides a comprehensive overview of current preclinical approaches and quantitative insights for optimizing L. lactis-based vaccines against parasitic diseases.