Uddin Muhammed Salah, Kaldis Angelo, Menassa Rima, Ortiz Guluarte José, Barreda Daniel R, Guan Le Luo, Alexander Trevor W
Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada.
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada.
Vaccines (Basel). 2024 Apr 1;12(4):375. doi: 10.3390/vaccines12040375.
is a bovine respiratory pathogen commonly associated with bacterial bronchopneumonia. Current vaccine strategies have shown variable efficacy in feedlot cattle, and therefore novel vaccines are needed. spores have been investigated as a mucosal vaccine platform, due to their ability to bind and present antigens to the mucosa and act as an adjuvant. The aim of this study was to develop two spore-based mucosal vaccines targeting and evaluate their immunogenicity in mice.
Two antigen constructs composed of cholera toxin B subunit, leukotoxin, and either the outer membrane protein PlpE (MhCP1) or GS60 (MhCP2) were synthesized, purified and then bound to spores as vaccines. In two separate mice trials, the spore-bound vaccines (Spore-MhCP1 and Spore-MhCP2) were administered to mice through intranasal and intragastric routes, while free antigens were administered intranasally and intramuscularly. Unbound spores were also evaluated intranasally. Antigen-specific serum IgG and mucosal IgA from bronchoalveolar lavage, feces, and saliva were measured after vaccination. Mice sera from all treatment groups were assessed for their bactericidal activity against .
In both mice experiments, intramuscular immunization induced the strongest serum IgG antibody response. However, the intranasal administration of Spore-MhCP1 and Spore-MhCP2 elicited the greatest secretory IgA-specific response against leukotoxin, PlpE, and GS60 in bronchoalveolar lavage, saliva, and feces ( < 0.05). Compared to the intranasal administration of free antigen, spore-bound antigen groups showed greater bactericidal activity against ( < 0.05).
Since intranasally delivered Spore-MhCP1 and Spore-MhCP2 elicited both systemic and mucosal immune responses in mice, these vaccines may have potential to mitigate lung infection in cattle by restricting colonization and proliferation in the respiratory tract. The efficacy of these mucosal spore-based vaccines merits further assessment against in cattle.
是一种常见的与牛细菌性支气管肺炎相关的牛呼吸道病原体。目前的疫苗策略在饲养场牛中显示出不同的效果，因此需要新型疫苗。由于孢子能够结合抗原并将其呈递给黏膜，还能作为佐剂，因此已被研究作为一种黏膜疫苗平台。本研究的目的是开发两种针对的基于孢子的黏膜疫苗，并评估它们在小鼠中的免疫原性。
合成、纯化了两种由霍乱毒素B亚基、白细胞毒素以及外膜蛋白PlpE（MhCP1）或GS60（MhCP2）组成的抗原构建体，然后将其作为疫苗与孢子结合。在两项独立的小鼠试验中，将结合孢子的疫苗（Spore-MhCP1和Spore-MhCP2）通过鼻内和胃内途径给予小鼠，同时将游离抗原通过鼻内和肌肉内途径给予。未结合的孢子也通过鼻内途径进行评估。接种疫苗后测量支气管肺泡灌洗、粪便和唾液中抗原特异性血清IgG和黏膜IgA。评估所有治疗组小鼠血清对的杀菌活性。
在两项小鼠实验中，肌肉内免疫诱导了最强的血清IgG抗体反应。然而，鼻内给予Spore-MhCP1和Spore-MhCP2在支气管肺泡灌洗、唾液和粪便中引发了针对白细胞毒素、PlpE和GS60的最大分泌型IgA特异性反应（P<0.05）。与鼻内给予游离抗原相比，结合孢子的抗原组对显示出更大的杀菌活性（P<0.05）。
由于鼻内给予的Spore-MhCP1和Spore-MhCP2在小鼠中引发了全身和黏膜免疫反应，这些疫苗可能有潜力通过限制在呼吸道中的定植和增殖来减轻牛的肺部感染。这些基于黏膜孢子的疫苗在牛中针对的疗效值得进一步评估。
