M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.
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.
['Ye|Ting|T|', 'Yue|Yan|Y|', 'Fan|Xiangmei|X|', 'Dong|Chunsheng|C|', 'Xu|Wei|W|', 'Xiong|Sidong|S|']
D000276:Adjuvants, Immunologic D000284:Administration, Oral D000818:Animals D000914:Antibodies, Viral D048271:Chitosan D003384:Coxsackievirus Infections D004195:Disease Models, Animal D029822:Enterovirus B, Human D018928:Immunity, Mucosal D007071:Immunoglobulin A, Secretory D007074:Immunoglobulin G D008297:Male D008807:Mice, Inbred BALB C D009205:Myocarditis D013601:T-Lymphocytes D019444:Vaccines, DNA D019562:Viral Load D014765:Viral Vaccines
M cell-targeting Mucosal immune response Viral myocarditis Coxsackievirus B3 DNA vaccine