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首页> 外文期刊>Chemical and Pharmaceutical Bulletin >Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities
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Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities

机译：生物相容性聚合物缀合的寡核苷酸化学结构的影响鼻腔抗体诱导的粘膜佐剂

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We have been investigating the potential of oligoarginine-linked polymers as an adjuvant for mucosal vaccination that induces immunoglobulin G (IgG) in systemic circulation and immunoglobulin A (IgA) secreted on the mucosa. Our latest infection experiments demonstrated that mice immunized nasally with a mixture of inactivated influenza viruses and poly(N-vinylacetamide-co-acrylic acid) (PNVA-co-AA) modified with D-octaarginine were perfectly protected from homologous virus infection. On the contrary, virus infection was observed in mice immunized with the antigen alone. This difference was presumably due to insignificant induction of secreted IgA on the nasal mucosa in the latter mice. Since it was unclear whether the current induction level was sufficient for heterologous virus infection, we evaluated the effects of the chemical structures of oligoarginines conjugated to PNVA-co-AA on induction of intranasal IgA. The number and optical activity of the arginine residues and the degree of modification with oligoarginines in the polymer backbone were listed as a factor that would influence IgA induction. Mouse experiments revealed that maximization of the modification resulted in an increase in adjuvant activities of oligoarginine-linked polymers most effectively. Glycine segments inserted between oligoarginines and the polymer backbone were a prerequisite for the maximization. The highest IgA level was observed when antigens were coadministered with diglycine-D-octaarginine-linked PNVA-co-AA.
机译：我们已经研究了寡核苷酸链接聚合物作为粘膜疫苗接种的辅助潜力，其诱导粘膜分泌的全身循环中的免疫球蛋白G（IgG）和免疫球蛋白A（IgA）。我们的最新感染实验证明，用灭活的流感病毒和聚（n-乙酰乙酰胺 - 丙烯酸）（PNVA-CO-AA）与D-Octaar荷氏菌的混合物免疫的小鼠完全免受同源病毒感染的影响。相反，在用抗原单独免疫的小鼠中观察到病毒感染。这种差异是由于后者小鼠鼻粘膜上的分泌IgA微不足道的诱导。由于目前尚不清楚当前的感应水平是否足以用于异源病毒感染，我们评估了缀合与PNVA-CO-AA的寡核苷酸化学结构对鼻内IgA诱导的影响。精氨酸残基的数量和光学活性和聚合物主链中的寡核苷酸的改性程度被列为影响IgA诱导的因素。小鼠实验表明，改性的最大化导致寡核苷酸连锁聚合物的佐剂活性增加。插入寡核苷酸和聚合物主链之间的甘氨酸段是最大化的先决条件。观察到最高IgA水平，当用二甘氨酸-D-OCTARININE连接的PNVA-CO-AA共同凝结抗原时。

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