Immunization of cows with novel core glycolipid vaccine induces anti-endotoxin antibodies in bovine colostrum
Immunization of cows with novel core glycolipid vaccine induces anti-endotoxin antibodies in bovine colostrum
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DOI：
10.1016/j.vaccine.2014.08.083
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发表时间：
2014-10-21
期刊：
影响因子：
5.5
通讯作者：
Lees, Andrew
中科院分区：
文献类型：
--
作者：
Cross, Alan S.;Karreman, Hubert. J.;Lees, Andrew
背景：肠道来源的革兰氏阴性细菌 (GNB) 脂多糖（LPS，或内毒素）的易位是全身炎症的一个来源，会加剧 HIV、心血管和胃肠道疾病以及营养不良。口服牛初乳 (BC) 可减少肠道屏障功能受损患者的内毒素血症。因此，富含 LPS 抗体的 BC 可能会改善内毒素血症相关的发病率。我们开发了一种解毒 J5 LPS/B 组脑膜炎球菌外膜蛋白 (J5dLPS/OMP) 疫苗，可诱导针对 LPS 高度保守核心区域的抗体，并防止异源 GNB 感染。我们现在检查该疫苗在 BC 中引发抗核心内毒素抗体的能力。方法：使用该疫苗与 FICA（第 1 组）或 Emulsigen-D (R)（第 2 组）佐剂组合对两组怀孕奶牛进行免疫。在血清和初乳中测量了对 J5 核心 LPS 抗原的抗体反应，并与市售兽医疫苗 (J5 Bacterin (R)) 引起的抗体水平进行比较，该疫苗由热灭活的大肠杆菌 O111、J5 突变细菌组成，从中纯化了 J5 LPS。 结果：J5dLPS/OMP 疫苗在所有七头奶牛中诱导了高滴度的针对 J5 LPS 的血清 IgG 抗体。初乳中产生了 IgG 和较小程度的 IgA 抗 J5 LPS 抗体。 J5dLPS/OMP 疫苗在小鼠中的免疫原性明显高于 J5 Bacterin (R)。富含抗 J5 LPS 抗体的 BC 降低了中性粒细胞减少大鼠（一种“肠漏”模型）的循环内毒素水平。结论：J5dLPS/OMP 疫苗在奶牛中引发高滴度的血清抗内毒素抗体，并传递至初乳。这种富含抗核心 LPS 抗体的 BC 有可能减少肠道屏障功能受损患者的内毒素血症并改善内毒素相关的全身炎症。由于该疫苗的免疫原性明显高于 J5 Bacterin (R) 疫苗，因此该 J5dLPS/OMP 疫苗可能也被证明对兽医适应症更有用。 (C) 2014 Elsevier Ltd. 保留所有权利。
Background: Translocation of gut-derived Gram-negative bacterial (GNB) lipopolysaccharide (LPS, or endotoxin) is a source of systemic inflammation that exacerbates HIV, cardiovascular and gastrointestinal diseases and malnutrition. The oral administration of bovine colostrum (BC) reduces endotoxemia in patients with impaired gut barrier function. Consequently, BC enriched in antibodies to LPS may ameliorate endotoxemia-related morbidities. We developed a detoxified J5 LPS/group B meningococcal outer membrane protein (J5dLPS/OMP) vaccine that induces antibodies against a highly conserved core region of LPS and protects against heterologous GNB infection. We now examine the ability of this vaccine to elicit anti-core endotoxin antibodies in BC.Methods: Two cohorts of pregnant cows were immunized with this vaccine in combination with FICA (Cohort 1) or Emulsigen-D (R) (Cohort 2) adjuvants. Antibody responses to the J5 core LPS antigen were measured in both serum and colostrum and compared to antibody levels elicited by a commercially available veterinary vaccine (J5 Bacterin (R)) comprised of heat-killed Escherichia coli O111, J5 mutant bacteria, from which the J5 LPS was purified.Results: The J5dLPS/OMP vaccine induced high titers of serum IgG antibody to J5 LPS in all seven cows. Both IgG and to a lesser extent IgA anti-J5 LPS antibodies were generated in the colostrum. The J5dLPS/OMP vaccine was significantly more immunogenic in mice than was the J5 Bacterin (R). BC enriched in anti-J5 LPS antibody reduced circulating endotoxin levels in neutropenic rats, a model of "leaky gut".Conclusion: The J5dLPS/OMP vaccine elicits high titers of serum anti-endotoxin antibodies in cows that is passed to the colostrum. This BC enriched in anti-core LPS antibodies has the potential to reduce endotoxemia and ameliorate endotoxin-related systemic inflammation in patients with impaired gut barrier function. Since this vaccine is significantly more immunogenic than the J5 Bacterin (R) vaccine, this J5dLPS/OMP vaccine might prove to be more useful for veterinary indications as well. (C) 2014 Elsevier Ltd. All rights reserved.