Modulation of Immunogenicity and Immunoprotection of Mucosal Vaccine Against Coxsackievirus B3 by Optimizing the Coadministration Mode ofLymphotactinAdjuvant

Abstract

Induction of potent mucosal immune response is a goal of current vaccine strategies against mucus-infectious pathogens such as Coxsackievirus B3 type (CVB3). We previously showed that administration of lymphotactin (LTN) as an adjuvant could enhance the specific immune responses against a mucosal gene vaccine, chitosan-pVP1, against CVB3. To optimize the coadministration mode of the mucosal adjuvant, we compared the mucosal immune responses induced by chitosan-DNA vaccine with different combinations of the target VP1 antigen gene and the adjuvant LTN gene. The two genes were either cloned in separate vectors or coexpressed as a fusion or bicistron protein in the same vector before encapsulation in chitosan nanoparticles. Four doses of various adjuvant-combined chitosan-DNA were intranasally administrated to mice before challenge with CVB3. The results indicated that chitosan-formulated pVP1-LTN fusion plasmid exhibited very weak improvement of CVB3-specific immune responses. Although the bicistronic coexpression of LTN with VP1 was expected to be powerful, this combination had enhanced effects on serum IgG and systemic T cell immune responses, but not on mucosal T cell immunity. Coimmunization with VP1 and LTN as separate chitosan-DNA formulation remarkably enhanced antibody and T cell immune responses both in systemic and mucosal immune compartments, leading to the most desirable preventive effect on viral myocarditis. Taken together, how the adjuvant is combined with the target antigen has a strong influence on the mucosal immune responses induced by mucosal DNA vaccines.

Mucosal co-immunization with AIM2 enhances protective SIgA response and increases prophylactic efficacy of chitosan-DNA vaccine against coxsackievirus B3-induced myocarditis

“…[36][37][38] However, delivery systems of mucosal vaccines remain a challenge to induce maximal mucosal protection simultaneously. In recent years, chitosan has gained increasing interest as a safe delivery system for plasmid DNA (pDNA).…”

Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis

“…The myocarditis model in BALB/c mice in our study was established by intraperitoneal injection of 3 times the 50% lethal dose (LD 50 ) of CVB3 (Nancy strain from Yingzhen Yang, as described above), as described previously (22). Seven days later, heart tissues were collected, sectioned, and stained with hematoxylin and eosin.…”

“…Seven days later, heart tissues were collected, sectioned, and stained with hematoxylin and eosin. The extent of myocardial lesions was quantified as described previously (22). To further evaluate the immune protection effect, mice were challenged with a lethal dose of CVB3 (5 times the LD 50 ), and the survival rate was monitored for up to 28 days.…”

“…The titers and neutralizing titers of CVB3-specific serum IgG and fecal SIgA were detected by enzyme-linked immunosorbent assay (ELISA) and microneutralization assays, as described previously (22).…”

MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis

“…Although much knowledge about CVB3 characteristics [4][5][6], as well as the control measures [7][8][9][10], has been gained using murine CVB3-induced myocarditis models, there are still no e ective preventative or therapeutic strategies available in the clinic. e major reason for this is that the pathogenesis of viral myocarditis is not well understood; therefore, there is an urgent need to explore further mechanisms underlying the interaction of CVB3 with the host and to nd new potential targets for viral myocarditis therapy.…”