Polyacrylate-Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus
Polyacrylate-Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus
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DOI：
10.3390/vaccines8010023
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发表时间：
2020-03-01
期刊：
影响因子：
7.8
通讯作者：
Toth, Istvan
中科院分区：
文献类型：
--
作者：
Faruck, Mohammad Omer;Zhao, Lili;Toth, Istvan
A组链球菌（GAS）相关的风湿性心脏病是GAS感染导致死亡的主要原因。虽然抗生素在大多数情况下可以治疗感染，但抗生素耐药性的增加，后期医疗干预和复发性感染是有效治疗GAS相关疾病的主要障碍。由于GAS感染通常起源于咽喉粘膜组织的细菌定植，因此可以产生全身和粘膜免疫应答的口服疫苗将解决与传统医学干预相关的问题。此外，口服疫苗更容易管理，而且对于大规模免疫接种来说更便宜。在这项研究中，来自GAS M蛋白的B细胞表位J8和通用辅助性T细胞泛HLA-DR结合表位肽（PADRE）与聚（丙烯酸甲酯）（PMA）缀合以形成自组装纳米颗粒疫苗候选物（PMA-P-J8）。在用缀合物单次口服免疫小鼠后诱导强的全身和粘膜免疫应答。产生的抗体是针对GAS临床分离株的调理剂，如在加强免疫后测量的。因此，我们开发了一种简单的缀合物作为有效的、不含佐剂的口服肽基疫苗。
Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.