REGULATION OF MEMBRANE FUSION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 与流感病毒有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引发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，为了改善流感交叉保护，可能需要在病毒进入位点诱导更广泛的免疫应答。 我们发现，当与霍乱毒素和免疫调节剂视黄酸和油酸一起施用时，灭活流感病毒抗原的皮肤免疫导致免疫后12周的完全保护。在经皮接种中使用佐剂导致显著的抗体滴度。 此外，用视黄酸接种的小鼠表现出增强的粘膜抗体应答，粘膜组织中抗体分泌细胞的数量增加，以及针对更高的流感致死剂量的保护。结果表明，灭活病毒与佐剂和/或免疫调节剂组合的经皮给药导致长期全身和粘膜应答，从而允许有效的保护性免疫。

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.