A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice |
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| Affiliation: | 1. Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, Lanzhou University, Lanzhou, China;2. Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China;3. Institute of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China;4. ABSL-3 Lab, Wuhan University, Wuhan, China;1. Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan, Hubei, PR China;2. Aeras, Rockville, MD, USA;3. Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA;1. Department of Pathogenic Organisms, Chongqing Medical University, Chongqing, China;2. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China;3. Department of Respiratory Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;1. Unit of Anti-tuberculosis Immunity, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China;2. Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;3. Department of Medical Microbiology and Parasitology, Shanghai Medical College, Fudan University, Shanghai 200032, China;4. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China;5. Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, 835 S. Wolcott Avenue, MC790, Chicago 60612, IL, United States;3. From the MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China |
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| 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 ± 0.38 log10 CFU) than traditional vaccine Bacillus Calmette–Guerin (BCG) (6.01 ± 0.33 log10 CFU) and PBS control (6.53 ± 0.26 log10 CFU) 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. |
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| Keywords: | Vaccine adjuvant Cationic liposomes DDA Poly I:C Cholesterol |
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