Immunotherapy for tobacco addiction may offer a safe, alternative treatment if the immunogenicity of the current nicotine vaccines can be improved. We show here that intradermal (ID) immunization induces the production of antibody directed against nicotine (NicAb) at a much higher level than conventional intramuscular (IM) immunization. The magnitude and duration of NicAb production was further increased robustly by non-inflammatory laser vaccine adjuvant (LVA), slightly inflammatory monophosphoryl lipid A (MPL) or a combination of MPL and CpG adjuvants. Consequently, significantly fewer vaccination doses were required to attain a high level of NicAb production for an extended period of time and reduce nicotine entry into the brain in the presence of LVA, MPL or MPL/CpG adjuvant, respectively. Yet, the potency of these adjuvants to augment ID nicotine vaccine immunogenicity came at the expense of local skin reactogenicity, with LVA causing little skin reaction and MPL/CpG stimulating overt skin irritation. These observations underscore a necessity of a balance between optimal adjuvant potency and undesired local reactogenicity. In summary, our study presents a novel approach to significantly improve nicotine vaccine immunogenicity by a combination of safe cutaneous vaccine adjuvants with ID immunization.

译文

如果可以改善当前尼古丁疫苗的免疫原性,则对烟草成瘾的免疫疗法可能会提供一种安全的替代疗法。我们在这里显示真皮内(ID)免疫诱导产生比常规肌内(IM)免疫高得多的针对尼古丁(NicAb)的抗体。通过非炎性激光疫苗佐剂(LVA),轻度炎性单磷酰脂质A(MPL)或MPL和CpG佐剂的组合,NicAb产生的强度和持续时间进一步提高。因此,分别在LVA,MPL或MPL / CpG佐剂的存在下,要长时间获得高水平的NicAb产量并减少尼古丁进入大脑,所需的疫苗剂量要少得多。但是,这些佐剂增强ID尼古丁疫苗免疫原性的能力是以牺牲局部皮肤反应原性为代价的,LVA引起的皮肤反应很小,而MPL / CpG刺激了明显的皮肤刺激性。这些观察结果强调了在最佳佐剂效力和不希望的局部反应原性之间取得平衡的必要性。总而言之,我们的研究提出了一种通过安全的皮肤疫苗佐剂与ID免疫相结合来显着提高尼古丁疫苗免疫原性的新方法。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录