Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization
Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization
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DOI：
10.1128/jvi.75.17.7956-7965.2001
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发表时间：
2001-09-01
影响因子：
5.4
通讯作者：
Payne, LG
中科院分区：
文献类型：
--
作者：
Chen, DX;Periwal, SB;Payne, LG
循环抗体和粘膜抗体都被认为对于保护人类和动物免受流感病毒感染很重要。然而，目前通过使用注射器和针头进行肌肉注射施用的灭活疫苗主要引发循环抗体。在这项研究中，我们报告通过独特的粉末输送系统进行表皮粉末免疫（EPI）可引发针对灭活流感病毒疫苗的血清和粘膜抗体。 EPI 后对流感疫苗的血清抗体反应通过霍乱毒素 (CT)、一种含有免疫刺激性 CpG 基序 (CpG DNA) 的合成寡脱氧核苷酸或这两种佐剂的组合的共同递送而增强。此外，在小肠、气管和阴道的唾液和粘膜灌洗液中检测到分泌性免疫球蛋白A（sIgA）抗体，尽管滴度远低于IgG滴度。通过测量培养的气管和小肠片段释放的抗体以及使用 ELISPOT 检测检测固有层中抗原特异性 IgA 分泌细胞，进一步显示了 sIgA 抗体的局部起源。使用含有 CT 或 CT 和 CpG DNA 的单剂量流感疫苗进行 EPI 可以提供针对 30 年前分离的流感病毒致命挑战的完全保护，而在没有佐剂的情况下需要初免和加强免疫才能提供保护。 EPI 能够引发增强的循环抗体和粘膜抗体反应，使其成为注射流感和其他疾病疫苗的有前途的替代品。
Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.