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新型黏膜佐剂马斯托帕兰-7可提高可卡因疫苗的疗效。

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

作者信息

St John Ashley L, Choi Hae Woong, Walker Q David, Blough Bruce, Kuhn Cynthia M, Abraham Soman N, Staats Herman F

机构信息

1Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, 169857 Singapore.

2Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA.

出版信息

NPJ Vaccines. 2020 Feb 5;5(1):12. doi: 10.1038/s41541-020-0161-1. eCollection 2020.

Abstract

Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, mastoparan-7 (M7), to achieve optimal IgA antibody responses in mucosal secretions and effective induction of humoral immunity using a short immunization protocol. This formulation, using a hapten-carrier system to deliver cocaine as antigen, also reduced cocaine penetration of the blood brain barrier and protected mice from its psychoactive effects by reducing cocaine-induced locomotion. Surprisingly, the magnitude of cocaine-specific antibody titers induced by each adjuvant was not the major determinant of functional protection from cocaine challenge. A side-by-side comparison of the two haptens, cocaine and its analog GNC demonstrated that cocaine haptenation resulted in superior functional protection when used in combination with the novel mucosal adjuvant, M7. These results provide a new potential strategy for combatting cocaine addiction through mucosal vaccination.

摘要

可卡因是已知最具效力和成瘾性的精神兴奋剂之一,目前尚无可用的药物疗法来治疗可卡因成瘾。在此,我们描述了一种新型可卡因疫苗,该疫苗采用黏膜佐剂和肥大细胞激活寡肽马斯托帕兰 -7(M7),通过简短的免疫方案在黏膜分泌物中实现最佳的IgA抗体反应并有效诱导体液免疫。这种使用半抗原 - 载体系统将可卡因作为抗原递送的制剂,还减少了可卡因对血脑屏障的穿透,并通过减少可卡因诱导的运动来保护小鼠免受其精神活性作用的影响。令人惊讶的是,每种佐剂诱导的可卡因特异性抗体滴度的大小并不是免受可卡因攻击的功能保护的主要决定因素。对两种半抗原可卡因及其类似物GNC的并列比较表明,当与新型黏膜佐剂M7联合使用时,可卡因半抗原化产生了更好的功能保护。这些结果为通过黏膜疫苗接种对抗可卡因成瘾提供了一种新的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ac/7002721/60fe1b0a19eb/41541_2020_161_Fig1_HTML.jpg

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