Enhanced resistance to coxsackievirus B3-induced myocarditis by intranasal co-immunization of lymphotactin gene encapsulated in chitosan particle.
Coxsackievirus B3 (CVB3) is a gastrointestinal virus causing myocarditis in human and mice. An ideal vaccine for CVB3-myocarditis requires both humoral and cellular immunity at systemic and mucosal compartments. We described here an enhancing strategy for chitosan-pVP1 vaccine by co-immunizing with lymphotactin (LTN) gene, a T cell-attractive-chemokine, encapsulated in chitosan particle to provide more protection against CVB3. Mice were intranasally co-immunized with 4 doses of chitosan-DNA vaccines separately encapsulating VP1 and LTN plasmids by 2 week-intervals and challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 alone, co-immunization with chitosan-pLTN significantly increased high-avidity-neutralizing antibody levels in serum and in intestinal mucosa, and promoted systemic and mucosal Th1 and CD8(+)CTL immune responses. Accordingly, enhanced resistance to CVB3-myocarditis was evidenced by reduced myocardial viral load, profound subsidence of myocarditis and increased survival rate. This strategy represents a promising platform for Th1 polarization and protection against mucosal infectious pathogens.
Yue
Yan
Y
Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Xu
Wei
W
Hu
Linkun
L
Jiang
Zhenggang
Z
Xiong
Sidong
S
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D048271:Chitosan / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control*; D029822:Enterovirus B, Human / Q000276:immunology*; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007114:Immunization; D008222:Lymphokines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D009500:Neutralization Tests; D012795:Sialoglycoproteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D008222:Lymphokines; D012795:Sialoglycoproteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; C018997:lymphotactin; D048271:Chitosan