title: M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.
abstract: Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development.
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China.
authors: Ting
authors: T
authors: Ye
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China.
authors: Yan
authors: Y
authors: Yue
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China.
authors: Xiangmei
authors: X
authors: Fan
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China.
authors: Chunsheng
authors: C
authors: Dong
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China.
authors: Wei
authors: W
authors: Xu
authors: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, PR China. Electronic address: sdxiongfd@126.com.
authors: Sidong
authors: S
authors: Xiong
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D048271:Chitosan / Q000008:administration & dosage*; D003384:Coxsackievirus Infections / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000473:pathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014765:Viral Vaccines; D048271:Chitosan
keywords: Coxsackievirus B3; DNA vaccine; M cell-targeting; Mucosal immune response; Viral myocarditis