Boerhout Eveline, Vrieling Manouk, Benedictus Lindert, Daemen Ineke, Ravesloot Lars, Rutten Victor, Nuijten Piet, van Strijp Jos, Koets Ad, Eisenberg Susanne
Ruminant Research and Development, MSD Animal Health, Wim de Körverstraat 35, 5830, AA, Boxmeer, The Netherlands.
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584, CL, Utrecht, The Netherlands.
Vet Res. 2015 Sep 28;46:115. doi: 10.1186/s13567-015-0243-7.
Vaccines against S. aureus bovine mastitis are scarce and show limited protection only. All currently available vaccines are applied via the parenteral (usually intramuscular) route. It is unknown, however, whether this route is the most suitable to specifically increase intramammary immunity to combat S. aureus at the site of infection. Hence, in the present study, immunization via mucosal (intranasal; IN), intramuscular (triangle of the neck; IM), intramammary (IMM) and subcutaneous (suspensory ligament; SC) routes were analyzed for their effects on the quantity of the antibody responses in serum and milk as well as the neutralizing capacity of the antibodies within serum. The experimental vaccine comprised the recombinant S. aureus immune evasion proteins extracellular fibrinogen-binding protein (Efb) and the leukotoxin subunit LukM in an oil-in-water adjuvant combined with a hydrogel and alginate. The highest titer increases for both Efb and LukM specific IgG1 and IgG2 antibody levels in serum and milk were observed following SC/SC immunizations. Furthermore, the harmful effects of Efb and leukotoxin LukMF' on host-defense were neutralized by serum antibodies in a route-dependent manner. SC/SC immunization resulted in a significant increase in the neutralizing capacity of serum antibodies towards Efb and LukMF', shown by increased phagocytosis of S. aureus and increased viability of bovine leukocytes. Therefore, a SC immunization route should be considered when aiming to optimize humoral immunity against S. aureus mastitis in cattle.
针对金黄色葡萄球菌引起的牛乳腺炎的疫苗稀缺，且仅显示出有限的保护作用。目前所有可用疫苗均通过肠胃外（通常为肌肉内）途径接种。然而，尚不清楚该途径是否最适合特异性增强乳腺内免疫力以对抗感染部位的金黄色葡萄球菌。因此，在本研究中，分析了通过黏膜（鼻内；IN）、肌肉内（颈部三角区；IM）、乳腺内（IMM）和皮下（悬韧带；SC）途径免疫对血清和乳汁中抗体反应量以及血清中抗体中和能力的影响。实验疫苗由重组金黄色葡萄球菌免疫逃避蛋白细胞外纤维蛋白原结合蛋白（Efb）和白细胞毒素亚基LukM组成，置于水包油佐剂中，并与水凝胶和藻酸盐结合。在进行SC/SC免疫后，观察到血清和乳汁中Efb和LukM特异性IgG1和IgG2抗体水平的滴度增加最高。此外，血清抗体以途径依赖的方式中和了Efb和白细胞毒素LukMF'对宿主防御的有害影响。SC/SC免疫导致血清抗体对Efb和LukMF'的中和能力显著增加，表现为金黄色葡萄球菌吞噬作用增强和牛白细胞活力增加。因此，旨在优化牛对金黄色葡萄球菌乳腺炎的体液免疫时，应考虑皮下免疫途径。
