Abstract:
Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.
摘要:
槟榔咀嚼成瘾是口腔粘膜下纤维化和口腔癌的主要原因,造成重大的社会经济负担。接种疫苗可以作为一种有希望的潜在补救措施,以减轻槟榔的滥用和打击意外过量。半抗原设计是槟榔碱疫苗开发的关键因素,它决定了候选疫苗的功效。在这里,我们报道了两种新型的基于槟榔碱的半抗原,并与牛血清白蛋白(BSA)缀合以产生免疫原,产生对槟榔碱具有高亲和力的抗体,但降低了对guvacoline的结合,对槟榔碱或guvacine没有亲和力。值得注意的是,Arec-N-BSA疫苗接种,通过四氢吡啶环上的N-位(叔胺基团),与Arec-CONH-BSA相比,导致更高的抗体亲和力,槟榔碱的镇痛减弱和低温减弱。