title: A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice.
abstract: Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400 nm and zeta potential of 40 mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell-mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41 ± 0.38log10CFU) than traditional vaccine Bacillus Calmette-Guerin (BCG) (6.01 ± 0.33log10CFU) and PBS control (6.53 ± 0.26log10CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine.
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors: Xun
authors: X
authors: Liu
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors: Zejiao
authors: Z
authors: Da
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors: Yue
authors: Y
authors: Wang
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors: Hongxia
authors: H
authors: Niu
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors: Ruiying
authors: R
authors: Li
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors: Hongjuan
authors: H
authors: Yu
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors: Shanshan
authors: S
authors: He
authors: ABSL-3 Lab, Wuhan University, Wuhan, China.
authors: Ming
authors: M
authors: Guo
authors: ABSL-3 Lab, Wuhan University, Wuhan, China.
authors: Yong
authors: Y
authors: Wang
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors: Yanping
authors: Y
authors: Luo
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors: Xingming
authors: X
authors: Ma
authors: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address: bdzhu@lzu.edu.cn.
authors: Bingdong
authors: B
authors: Zhu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008081:Liposomes / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis; D010316:Particle Size; D011070:Poly I-C / Q000008:administration & dosage / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; C026584:dioctadecyltrimethylammonium; D002784:Cholesterol; D011070:Poly I-C
keywords: Cationic liposomes; Cholesterol; DDA; Mycobacterium tuberculosis; Poly I:C; Vaccine adjuvant