REGULATION OF MEMBRANE FUSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 与流感病毒相关的呼吸道疾病可以通过接种疫苗来预防。目前的灭活流感疫苗在诱导足以控制病毒复制的系统性病毒特异性抗体方面是有效的。然而，为了加强流感的交叉保护，可能需要在病毒进入部位诱导更广泛的免疫反应。我们发现，用灭活的流感病毒抗原与霍乱毒素和免疫调节剂维甲酸和油酸一起进行皮肤免疫，可在免疫后12周获得完全保护。在经皮接种中使用佐剂可产生大量抗体滴度。 此外，接种维甲酸的小鼠显示出增强的粘膜抗体反应，增加了粘膜组织中抗体分泌细胞的数量，并对更高剂量的流感具有保护作用。结果表明，灭活病毒经皮给药结合佐剂和/或免疫调节剂可产生长期的全身和粘膜反应，从而产生有效的保护性免疫。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The respiratory illnesses related to influenza virus can be prevented by vaccination. The current inactivated influenza vaccine is effective in eliciting systemic virus-specific antibodies sufficient to control viral replication. However, in order to improve influenza cross-protection the induction of a broader immune response at the site of viral entry may be required. We found that skin immunization of inactivated influenza virus antigen when administered with cholera toxin and the immunomodulators, retinoic acid and oleic acid, results in complete protection 12 weeks post immunization. The use of adjuvants in transdermal vaccination results in substantial antibody titers. In addition, mice vaccinated with retinoic acid show an enhanced mucosal antibody response, increased number of antibody secreting cells in the mucosal tissue, and protection against a higher influenza lethal dose. The results show that transdermal administration of inactivated virus in combination with adjuvants and/or immunomodulators results in long-term systemic and mucosal responses allowing for an effective protective immunity.