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

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Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.
npj Vaccines ( IF 6.9 ) Pub Date : 2020-02-05 , DOI: 10.1038/s41541-020-0161-1
Ashley L St John _{1,

2,

3,

4} , Hae Woong Choi _{2,

5} , Q David Walker ₆ , Bruce Blough ₇ , Cynthia M Kuhn ₆ , Soman N Abraham _{1,

2,

8,

9} , Herman F Staats _{2,

6,

10}

Affiliation

1Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, 169857 Singapore.
2Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA.
3Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228 Singapore.
4SingHealth Duke-NUS Global Health Institute, Singapore, 168753 Singapore.
Present Address: Korea University, Division of Life Sciences, 108 Hana-Science Building, 145 Anam-ro, Seongbuk-gu, Seoul, South Korea.
5Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710 USA.
6Center for Drug Discovery, RTI International, Research Triangle Park, Durham, NC 27709 USA.
7Department of Immunology, Duke University Medical Center, Durham, NC 27710 USA.
8Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA.
9Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710 USA.

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.

中文翻译：

新型粘膜佐剂 Mastoparan-7 可提高可卡因疫苗的功效。

可卡因是已知最有效和最容易上瘾的精神兴奋剂之一，并且没有可用的药物疗法来治疗可卡因成瘾。在这里，我们描述了一种新型可卡因疫苗，采用粘膜佐剂和肥大细胞激活寡肽 mastoparan-7 (M7)，以在粘膜分泌物中实现最佳 IgA 抗体反应，并使用简短的免疫方案有效诱导体液免疫。该制剂使用半抗原载体系统传递可卡因作为抗原，还减少了可卡因对血脑屏障的渗透，并通过减少可卡因引起的运动来保护小鼠免受其精神影响。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针对可卡因攻击的功能性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，当与新型粘膜佐剂 M7 组合使用时，可卡因半抗原化可产生卓越的功能保护。这些结果为通过粘膜疫苗接种对抗可卡因成瘾提供了新的潜在策略。

更新日期：2020-02-05

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