Blanco Federico Carlos, Onnainty Renée, Marini María Rocío, Klepp Laura Inés, García Elizabeth Andrea, Vazquez Cristina Lourdes, Canal Ana, Granero Gladys, Bigi Fabiana
Instituto de Agrobiotecnología y Biología Molecular, (IABIMO) INTA-CONICET, Instituto de Biotecnología, CICVyA, Instituto Nacional de Tecnología Agropecuaria (INTA), N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA)-CONICET, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
Pathogens. 2025 Jun 16;14(6):592. doi: 10.3390/pathogens14060592.
is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from and , has demonstrated protective efficacy against in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of -challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.
是牛结核病（bTB）的致病病原体，牛结核病会影响牛和包括人类在内的其他哺乳动物。目前，尚无针对bTB的有效疫苗，这凸显了新型免疫策略的必要性。M72融合蛋白由源自和的三种多肽组成，在与AS01E佐剂联合使用时，已在临床试验中证明对具有保护效力。鉴于纳米胶囊制剂作为疫苗递送系统已确立的功效，本研究评估了一种将卡介苗（BCG）与全长M72或与链球菌白蛋白结合域融合的截短M72（ABDsM72）相结合的新型免疫策略。两种抗原均封装在壳聚糖/海藻酸盐纳米胶囊中，并在小鼠攻击模型中进行评估。与单独使用卡介苗相比，先用卡介苗进行初次免疫，然后用M72进行加强免疫可显著改善脾脏保护，但并未增强肺部保护。值得注意的是，用ABDsM72进行加强免疫进一步增加了感染小鼠肺部CD4+KLRG1-CXCR3+T细胞的比例，这是保护性免疫的关键相关因素。这些发现表明，壳聚糖/海藻酸盐封装的抗原可增强卡介苗诱导的免疫力，支持它们作为控制bTB的下一代候选疫苗的潜力。
