Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine delivery
S. Sakuma, M. Suita, S. Inoue, Y. Marui, K. Nishida, Y. Masaoka, M. Kataoka, S. Yamashita, N. Nakajima, N. Shinkai, H. Yamauchi, K. Hiwatari, H. Tachikawa, R. Kimura, T. Uto, M. Baba
Mol. Pharmaceutics, Just Accepted
Publication Date (Web): September 6, 2012 (Article)
DOI: 10.1021/mp300329r
We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified with D-octaarginine, which is a typical cell-penetrating peptide, as a carrier for mucosal vaccine delivery. Mice were nasally inoculated 4 times every 7th day with PBS containing ovalbumin with or without the D-octaarginine-linked polymer. The polymer enhanced the production of ovalbumin-specific immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells appeared to stimulate IgA production. Ovalbumin transferred to systemic circulation possibly enhanced IgG production. An equivalent dose of the cholera toxin B subunit (CTB), which was used as a positive control, was superior to the polymer in enhancing antibody production; however, dose escalation of the polymer overcame this disadvantage. A similar immunization profile was also observed when ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a vaccine-specific immune response identical to that induced by CTB, irrespective of the antibody type, when its dose was 10 times that of CTB. Our cell-penetrating peptide-linked polymer is a potential candidate for antigen carriers that induce humoral immunity on the mucosal surface and in systemic circulation when nasally co-administered with antigens.
Keyword: Peptide Analysis Services