Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities

• Published in: Chemical & pharmaceutical bulletin Vol. 66; no. 4; pp. 375 - 381
• Main Authors: Mohri, Kohta, Miyata, Kohei, Egawa, Tomomi, Tanishita, Sohei, Endo, Rikito, Yagi, Haruya, Ukawa, Masami, Ochiai, Kyohei, Hiwatari, Ken-ichiro, Tsubaki, Kazufumi, Shigeno, Koichi, Tobita, Etsuo, Uto, Tomofumi, Baba, Masanori, Sakuma, Shinji
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acrylic acid; Adjuvants, Immunologic - chemistry; Animals; Antibodies - chemistry; Antibodies - immunology; Antigens; Arginine; Arginine - analogs & derivatives; Arginine - chemistry; Backbone; Biocompatibility; Biocompatible Materials - chemistry; cell-penetrating peptide; Female; Glycine; Homology; Immunization; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Infections; Influenza; Maximization; Mice; Mice, Inbred BALB C; Molecular Structure; Mucosa; mucosal adjuvant; mucosal vaccination; Mucous Membrane - chemistry; Mucous Membrane - immunology; Nasal Cavity - immunology; oligoarginine; oligoarginine-linked polymer; Optical activity; Polymers; Polymers - chemistry; Vaccination; Viruses; mucosal vaccination; oligoarginine-linked polymer; mucosal adjuvant; cell-penetrating peptide; oligoarginine
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c17-00834

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.