title: CD226 as a genetic adjuvant to enhance immune efficacy induced by Ag85A DNA vaccination.
abstract: Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium tuberculosis. Many studies on animal models have shown that vaccination with the recombinant Ag85A-DNA or Ag85A protein induces powerful immune response. However, these vaccines cannot generate sufficient protective immunity in the systemic compartment. CD226, a member of the immunoglobulin superfamily, is expressed in the majority of NK cells, T cells, monocytes, and platelets, and can be served as a co-stimulator that contributes to multiple innate and adaptive responses. However, there has been no study where either CD226 protein or DNA has been used as an adjuvant for vaccine development. The aim of this study was to develop a novel Ag85A DNA vaccine with CD226 as the genetic adjuvant to increase the immune efficacy induced by Ag85A. Oral vaccination with pcDNA3.1-Ag85A-CD226 DNA induced potent immune responses in mice. CD226 was an effective genetic adjuvant that improved the immune efficacy induced by Ag85A and enhanced the activity of cytotoxic T lymphocytes (CTL) and NK cells in mice. Th1 dominant cytokines (i.e. IL-2, IFN-γ and TNF-α), cellular immunity (i.e. CD4(+)IFN-γ(+)T cells and CD8(+)IFN-γ(+)T cells in splenocytes) and MLNs were also significantly elevated by pcDNA3.1-Ag85A-CD226 DNA vaccination. Our results suggest that CD226 is an effective adjuvant to enhance the immune efficacy induced by Ag85A. Our findings provide a new strategy for the development of a DNA vaccine co-expressing Ag85A and CD226.
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China; Department of Immunology and Microbiology, Liaoning College of Health Vocational Technology, No. 2, Qiaosong Road, Shenyang 110101, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Lixuan
authors.initials: L
authors.lastname: Sang
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Danan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Shan
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Rood, Heping District, Shenyang 110001, PR China. Electronic address: cllu@mail.cmu.edu.cn.
authors.forename: Changlong
authors.initials: C
authors.lastname: Lu
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D056724:Immunity, Humoral; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016207:Cytokines; D004269:DNA, Bacterial; D019444:Vaccines, DNA; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: Ag85A; CD226; DNA vaccine; Genetic adjuvant