One of the research areas of our laboratory is to focus on study of immune tolerance and immune regulation. The regulatory T (Treg) suppressor cells are believed to play a central role in the prevention of autoimmune and chronic inflammatory diseases. Treg cells include naturally occurring CD4+CD25+ T cells (nTreg), T regulatory type 1 (Tr1) and Th3 cells. However, the induction of Treg, particularly the antigen specific Treg in vivo, has proven to be difficult. We recently discovered that co-vaccination with DNA and its cognate protein leads to a novel phenomenon of induction of antigen specific inducible Treg (iTreg) (Jin H. et al., 2005; Kang Y. et al., 2007; Li J. et al., 2008). Generally, a protein or DNA based vaccine activates immune responses via the activation of DC. However, the co-delivery of DNA+protein together could interact with professional Antigen Presenting Cells, such as Dendritic Cells (DCs), in a way that is different than with either alone. Such interaction may lead to not only influence the outcome of DCs but also the subsequent immune responses. As we have demonstrated, this co-delivery elicits an antigen specific Treg, or iTreg that is caused by the fact that protein together with its encoding DNA vaccine conversely induces the DC into tolerogenic status. The iTreg possesses potent peripheral tolerance feature in an antigen specific manner (Jin H. et al., 2008a and 2008b). This co-immunization induces tolerogenic DC can produce high level of IL-10 with a CD11c+CD40lowphenotype.
Based on these observations, our goals are as following:
- To understand the fundamental differences of the functions of DC after a single stimulation with either DNA or protein compared to stimulations with a protein and DNA mixture
- To apply this co-immunization as an immunotherapeutic strategy to develop novel treatments against various immunological disorders including autoimmune diseases, asthma and allergy. Since some of the immunological disorders are caused by or highly associated with activations of pathogenic T cells that are triggered by some known auto-antigens, these pathogenic T cells non-stop attack self-organs until their eliminations. An approach pacifying these pathogenic cells could ease the attack and become an important strategy for the treatment or even cure of these diseases.
To demonstrate that this is feasible, we have examined the concept of co-immunization vaccine against Type 1 Diabetes in a murine NOD model. We showed that the T1D was preventable by using co-immunization of insulin with its DNA vaccine encoding the proinsulin gene (Zhang W. et al., 2010). Thus, we decided to test a similar approach with vaccines against multiple sclerosis, rheumatoid arthritis, and asthmas.
- Wenjuan Zhang, Huali Jin, Yang Yu, Xiaolin Li, Zheng Ding and Bin Wang. Co-immunization of DNA and Protein to prevent diabetes in NOD mice. Hum Gen Therapy, 2011, 21:1-8.
- Xu H, Zhao G, Huang X, Ding Z, Wang J, Wang X, Cheng Y, Kang Y, Wang B. CD40-Expressing Plasmid Induces Anti-CD40 Antibody and Enhances Immune Responses to DNA Vaccination. J Gene Med. 2010 Jan;12(1):97-106.
- Jin J, Ding Z, Meng F, Liu Q, Ng T, Hu Y, Zhao G, Zhai B, Chu HJ, Wang B. An immunotherapeutic treatment against flea allergy dermatitis in cats by co-immunization of DNA and protein vaccines. Vaccine. 2010 Feb 23;28(8):1997-2004.
- Zou Q, Zhong Y, Su H, Kang Y, Jin J, Liu Q, Geng S, Zhao G, Wang B. Enhancement of humoral and cellular responses to HBsAg DNA vaccination by immunization with praziquantel through inhibition TGF-beta/Smad2,3 signaling. Vaccine. 2010 Feb 23;28(8):2032-8.
- Kang Y, Zhao J, Liu Y, Chen A, Zheng G, Yu Y, Mi J, Zou Q, Wang B. FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitis. J Gene Med. 2009 Nov;11(11):1064-70.
- Zhang W, Du X, Zhao G, Jin H, Kang Y, Xiao C, Liu M, Wang B. Levamisole is a potential facilitator for the activation of Th1 responses of the subunit HBV vaccination. Vaccine. 2009 Aug 6;27(36):4938-46.
- Zhao G, Jin H, Li J, Su B, Du X, Kang Y, Wang X, Wang B. PyNTTTTGT prototype oligonucleotide IMT504, a novel effective adjuvant of the FMDV DNA vaccine. Viral Immunol. 2009 Apr;22(2):131-8.
- Huali Jin, Chong Xiao, Shuang Geng, Yanxin Hu, Ruiping She, Yang Yu, Youmin Kang and Bin Wang. Protection from asthma due to antigen specific Tr cells induced by co-vaccination. Eur. J. Immunol. 2008. 38: 2452–2464.
- Wang J, Su B, Ding Z, Du X, Wang B. Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. Biochem Biophys Res Commun. 2008 Aug 1;372(3):491-6.
- Li J, Jin H, Zhang F, Du X, Zhao G, Yu Y, Wang B. Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells. J Gene Med. 2008 Jul;10(7):810-20.
- Kang Y, Xu L, Wang B, Chen A, Zheng G. Cutting edge: Immunosuppressant as adjuvant for tolerogenic immunization. J Immunol. 2008 Apr 15;180(8):5172-6.
- Huali Jin, Youmin Kang, Lin Zhao, Chong Xiao, Xiaogang Du, Xiaolin, Sun, Terry Ng, Steve Chu and Bin Wang. Prevention of Flea Allergy Dermatitis via Induction of Antigen Specific Adaptive TR Cells by Co-Inoculation of DNA plus Protein Regimens. J. Immunol. 2008, 180: 5360–5372.
- Li J, Jin H, Zhang A, Li Y, Wang B, Zhang F. Enhanced contraceptive response by co-immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary. J Gene Med. 2007 Dec;9(12):1095-103.