Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing
Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing
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DOI：
10.1038/mi.2008.59
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发表时间：
2008-11-01
影响因子：
8
通讯作者：
Sutton, P.
中科院分区：
文献类型：
--
作者：
Wee, J. L. K.;Scheerlinck, J-P Y.;Sutton, P.
使用大型动物模型，我们评估了通过粘膜感染部位输送流感疫苗是否可以提高疫苗有效性。出乎意料的是，用极低抗原剂量（0.04μg流感病毒）进行肺部免疫诱导的血清抗体水平相当于目前人类疫苗等效物（15μg无佐剂流感病毒，皮下注射）所产生的血清抗体水平，并且肺粘膜抗体的水平要高得多。肺部疫苗接种后这种有效反应的诱导取决于 ISCOMATRIX 佐剂的添加和深肺递送。以血凝抑制为标志的功能性抗体活性仅存在于通过肺部接受佐剂疫苗的动物的肺部，这表明这种方法可能会转化为改善的保护作用。与现有疫苗相比，抗原剂量减少了 375 倍，粘膜抗体反应得到改善，这表明，在流感大流行的情况下，当疫苗供应不太可能满足需求时，通过肺部途径的粘膜递送可能特别重要。
Using a large animal model, we evaluated whether delivery of influenza vaccine via its mucosal site of infection could improve vaccine effectiveness. Unexpectedly, pulmonary immunization with extremely low antigen doses (0.04 mu g influenza) induced serum antibody levels equivalent to those resulting from a current human vaccine equivalent (15 mu g unadjuvanted influenza, subcutaneously) and vastly superior lung mucosal antibodies. Induction of this potent response following lung vaccination was dependent on addition of ISCOMATRIX adjuvant and deep lung delivery. Functional antibody activity, marked by hemagglutination inhibition, was only present in the lungs of animals that received adjuvanted vaccine via the lungs, suggesting this approach could potentially translate to improved protection. The 375-fold reduction in antigen dose and improved mucosal antibody responses, compared to the current vaccine, suggests that mucosal delivery via the pulmonary route may be particularly relevant in the event of an influenza pandemic, when vaccine supplies are unlikely to meet demand.