Application of the Sponge Model Implants in the Study of Vaccine Memory in Mice Previously Immunized with LBSap

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Considering the large number of candidates in vaccine testing studies against different pathogens and the amount of time spent in the pre- and clinical trials, there is a pressing need to develop an improved in vivo system to quickly screen vaccine candidates. The model of a polyester-polyurethane sponge implant provides a rapid analysis of the specific stimulus-response, allowing the study of a compartmentalized microenvironment. The sponge implant’s defined measurements were standardized as a compartment to assess the immune response triggered by vaccinal antigen. The LBSap vaccine (composed by Leishmania braziliensis antigens associated with saponin adjuvant) was used in the sponge model to assess the antigen-specific immunological biomarker, including memory generation after initial contact with the antigen. Mice strains (Swiss, BALB/c, and C57BL/6) were previously immunized using LBSap vaccine followed by an antigenic booster performed inside the sponge implant. The sponge implants were assessed after 72 hours, and the immune response pattern was analyzed according to leukocyte immunophenotyping and cytokine production. After LBSap vaccination, the innate immune response of the antigenic booster in the sponge implants demonstrated higher levels in the Ly+ neutrophils and CD11c+ dendritic cells with reduced numbers of F4/80+ macrophages. Moreover, the adaptive immune response in Swiss mice demonstrated a high CD3+CD4+ T-cells frequency consisting of an effector memory component in addition to a cytoxicity response (CD3+CD8+ T-cells), displaying the central memory biomarker. The major cell surface biomarker in the BALB/c mice strain was related to CD3+CD4+ effector memory while the increased CD3+CD8+ effector memory was highlighted in C57/BL6. The cytokine profile was more inflammatory in Swiss mice, with the highest levels of IL-6, TNF, IFN-g, and IL-17, while the same cytokine was observed in in C57BL/6 yet modulated by enhanced IL-10 levels. Similar to Swiss mice, BALB/c mice triggered an inflammatory environment after the antigenic booster in the sponge implant with the increased levels in the ILL-6, TNF, and IFN-g. The results highlighted how genetic background can influence populations involved in the immune response and indicated that it is possible to use this model to optimize and monitor the innate and adaptive immune responses of vaccine candidates. In this sense, these results could guide the choice of the most appropriate experimental model in biomolecule tests, considering that the particularities of each mouse strain influenced the dynamics of the immune response.

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