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在小母牛中产生的针对金黄色葡萄球菌CP5裂解物以及用免疫刺激复合物基质佐剂配制的重组抗原疫苗的抗体的免疫反应及功能作用。

Immune response and functional role of antibodies raised in heifers against a Staphylococcus aureus CP5 lysate and recombinant antigens vaccine formulated with Iscom Matrix adjuvant.

作者信息

Camussone C M, Pujato N, Renna M S, Veaute C M, Morein B, Marcipar I S, Calvinho L F

机构信息

Estación Experimental Agropecuaria Rafaela, INTA, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina; Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

出版信息

Vet Immunol Immunopathol. 2014 Dec 15;162(3-4):96-107. doi: 10.1016/j.vetimm.2014.10.004. Epub 2014 Oct 14.

Abstract

Staphylococcus aureus is the most frequently isolated pathogen from bovine intramammary infections worldwide. Commercially available vaccines for mastitis control are composed either of S. aureus lysates or inactivated whole-cells formulated with traditional adjuvants. We recently showed the ability of a S. aureus CP5 lysate vaccine adjuvanted with Iscom Matrix to generate a longer lasting specific antibody response in blood and milk, with improved opsonic capacity, compared with a S. aureus CP5 whole-cell formulation. The aim of the present study was to obtain an experimental immunogen composed of lysed cells of a CP5 S. aureus strain supplemented with recombinant clumping factor A, fibronectin binding protein A and β-toxin formulated with Iscom Matrix, characterize the immune response generated when immunizing pregnant heifers and assess the functional role of antibodies raised against this immunogen in experimental models. Both a lysate vaccine and a lysate+recombinant antigens vaccine elicited antibodies that promoted neutrophil phagocytosis and inhibited internalization into mammary epithelial cells, in vitro. Incorporation of defined antigenic molecules to the lysate formulation elicited a strong specific humoral immune response against both lysate and recombinant antigens and was associated with higher expression of regulatory and pro-inflammatory cytokines. In addition, antibodies were efficient for blocking S. aureus binding to bovine fibrinogen and fibronectin, and neutralizing β-toxin effect in vitro, placing these antigens as candidates to be included in a formulation directed to prevent staphylococcal bovine mastitis.

摘要

金黄色葡萄球菌是全球范围内从牛乳房内感染中最常分离出的病原体。用于控制乳腺炎的市售疫苗由金黄色葡萄球菌裂解物或与传统佐剂配制的灭活全细胞组成。我们最近发现,与金黄色葡萄球菌CP5全细胞制剂相比,用免疫刺激复合物基质佐剂的金黄色葡萄球菌CP5裂解物疫苗能够在血液和乳汁中产生更持久的特异性抗体反应,并提高调理吞噬能力。本研究的目的是获得一种实验性免疫原,该免疫原由CP5金黄色葡萄球菌菌株的裂解细胞组成,并补充重组聚集因子A、纤连蛋白结合蛋白A和β毒素,用免疫刺激复合物基质配制,表征免疫怀孕小母牛时产生的免疫反应,并评估在实验模型中针对该免疫原产生的抗体的功能作用。在体外,裂解物疫苗和裂解物+重组抗原疫苗都能诱导出促进中性粒细胞吞噬并抑制其内化进入乳腺上皮细胞的抗体。将特定抗原分子掺入裂解物制剂中可引发针对裂解物和重组抗原的强烈特异性体液免疫反应,并与调节性和促炎性细胞因子的更高表达相关。此外,抗体在体外能有效阻断金黄色葡萄球菌与牛纤维蛋白原和纤连蛋白的结合,并中和β毒素的作用,这些抗原有望被纳入预防牛葡萄球菌性乳腺炎的制剂中。

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