Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge.
Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge.
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DOI：
10.1038/s41541-021-00329-0
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发表时间：
2021-05-13
期刊：
影响因子：
9.2
通讯作者：
Norton EB
中科院分区：
文献类型：
--
作者：
Stone AE;Scheuermann SE;Haile CN;Cuny GD;Velasquez ML;Linhuber JP;Duddupudi AL;Vigliaturo JR;Pravetoni M;Kosten TA;Kosten TR;Norton EB
芬太尼是导致物质使用障碍(SUD)过量死亡毁灭性增加的主要原因。针对芬太尼的疫苗可能是一种强大的免疫疗法。在这里，我们评估了芬太尼为基础的半抗原结合抗原疫苗的佐剂和递送策略。我们通过肌肉、舌下或鼻腔给药的方式测试了来源于不耐热的大肠杆菌毒素的佐剂，包括dmLT和LTA1。我们的结果显示抗芬太尼血清抗体和免疫后骨髓中的抗体分泌细胞在佐剂(明矾、dmLT或LTA1)中观察到最高水平。使用LTA1或dmLT佐剂的疫苗可诱导最高水平的抗芬太尼抗体，而明矾可产生最高水平的抗载体蛋白抗体。舌下注射dmLT或鼻腔注射LTA1可最有力地阻断芬太尼诱导的镇痛和与抗Fen IgA密切相关的中枢神经系统的穿透。总之，这项研究表明，dmLT或LTA1佐剂以及粘膜递送可能是改善疫苗效力的有吸引力的策略。
Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens. We tested adjuvants derived from the heat-labile toxin of E. coli including dmLT and LTA1 by intramuscular, sublingual or intranasal delivery. Our results show anti-fentanyl serum antibodies and antibody secreting cells in the bone-marrow after vaccination with highest levels observed with an adjuvant (alum, dmLT, or LTA1). Vaccine adjuvanted with LTA1 or dmLT elicited the highest levels of anti-fentanyl antibodies, whereas alum achieved highest levels against the carrier protein. Vaccination with sublingual dmLT or intranasal LTA1 provided the most robust blockade of fentanyl-induced analgesia and CNS penetration correlating strongly to anti-FEN IgA. In conclusion, this study demonstrates dmLT or LTA1 adjuvant as well as mucosal delivery may be attractive strategies for improving the efficacy of vaccines against SUD.
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影响因子：
3.4
作者：
Eastwood EC;Phillips TJ
通讯作者：
Phillips TJ
DOI：
10.4049/jimmunol.1302743
发表时间：
2014-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Heine SJ;Diaz-McNair J;Andar AU;Drachenberg CB;van de Verg L;Walker R;Picking WL;Pasetti MF
通讯作者：
Pasetti MF
影响因子：
5.5
作者：
Hayden, Celine A.;Streatfield, Stephen J.;Howard, John A.
通讯作者：
Howard, John A.
影响因子：
4.9
作者：
Barrientos, Rodell C.;Bow, Eric W.;Matyas, Gary R.
通讯作者：
Matyas, Gary R.
影响因子：
5.5
作者：
Alving, Carl R.;Matyas, Gary R.;Torres, Oscar;Jalah, Rashmi;Beck, Zoltan
通讯作者：
Beck, Zoltan