Challenges in mucosal vaccination of cattle
Challenges in mucosal vaccination of cattle
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DOI：
10.1016/j.vetimm.2008.10.297
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发表时间：
2009-03-15
影响因子：
1.8
通讯作者：
Hodgins, D. C.
中科院分区：
文献类型：
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作者：
Shewen, P. E.;Carrasco-Medina, L.;Hodgins, D. C.
对许多传染病的粘膜入口以及粘膜免疫反应与保护的相关性的认识鼓励了通过粘膜途径（主要是口服和鼻内）施用的疫苗的开发，以分别刺激肠道和鼻咽淋巴组织。口服途径对于牛和其他反刍动物来说是有问题的，因为抗原在进入肠道之前很可能在瘤胃中降解。另一方面，如果疫苗抗原由苜蓿等纤维饲料表达，则可以利用反刍在啃咬过程中暴露鼻咽组织。饲喂表达溶血曼海姆氏菌 Lkt50 的苜蓿后，小牛的鼻分泌物中抗白细胞毒素 (Lkt) IgA 增加，有证据表明这种疫苗接种可以预防实验诱发的肺炎。鼻内疫苗接种是用于预反刍犊牛的另一种方法。鼻内施用携带溶血支原体可溶性抗原（包括天然 Lkt）的 ISCOM，在 4 周和 6 周龄接种疫苗后诱导鼻分泌物中出现 Lkt 特异性 IgA。皮下 (s.c.) 注射同一疫苗可在血清和鼻分泌物中诱导 Lkt 特异性 IgG，而皮下注射 (s.c.) 则可在血清和鼻分泌物中诱导 Lkt 特异性 IgG商业溶血支原体疫苗的注射则没有这种效果。无论采用何种疫苗接种策略，都很难评估粘膜施用疫苗的免疫原性，因为分泌抗体的产生往往是短暂的，并且在没有持续抗原刺激的情况下它们不会持续存在于粘膜表面。另一个挑战是证明疫苗对实验感染的功效。对粘膜接种疫苗的动物的保护很可能来自回忆反应，尽管这种反应足以应对自然诱发肺炎时发生的更长时间和渐进的感染，但这种反应可能不足以抵消实验性肺部输送大量有毒细菌的影响。 (C) 2008 Elsevier B.V. 保留所有权利。
Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. The oral route is problematic in cattle and other ruminants where antigen degradation in the rumen is likely, prior to transit to the intestine. On the other hand, rumination can be exploited for exposure of nasopharyngeal tissues during cudding if vaccine antigen is expressed by a fibrous feed like alfalfa. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. Intranasal vaccination is an alternative approach for use in pre-ruminating calves. Intranasal administration of ISCOMs carrying soluble antigens of M. haemolytica, including native Lkt, induced Lkt specific IgA in nasal secretions after vaccination at 4 and 6 weeks of age. Subcutaneous (s.c.) administration of the same vaccine induced Lkt specific IgG in both serum and nasal secretions, whereas s.c. administration of a commercial M. haemolytica vaccine did not. Regardless of the vaccination strategy employed it is difficult to assess the immunogenicity of mucosally administered vaccines because production of secreted antibodies tends to be transient, and they do not persist on the mucosal surface in the absence of ongoing antigenic stimulation. An additional challenge is demonstration of vaccine efficacy in response to experimental infection. Protection of the mucosally vaccinated animal will most probably result from recall response, which may not amplify sufficiently to counter the effects of experimental pulmonary delivery of a large bolus of virulent bacteria, even though the response would suffice over the more prolonged and gradual infection that occurs in natural induction of pneumonia. (C) 2008 Elsevier B.V. All rights reserved.