Davood Mansury1,2, Kiarash Ghazvini1,2, Saeid Amel Jamehdar1,2, Ali Badiee3,4, Mohsen Tafaghodi3,4, Amin Reza Nikpoor5, Yousef Amini6, Mahmoud Reza Jaafari3,4,7. 1. Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 6. Department of Microbiology and Virology, School of Medicine, Zahedan University of Medical Science, Zahedan, Iran. 7. Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract
BACKGROUND: Due to the ineffectiveness of the BCG vaccine, especially in adult pulmonary tuberculosis (TB), and variable efficacies against childhood forms of TB, developing an effective TB vaccine is a major priority in controlling this disease. The aim of this study was to evaluate the immunogenicity of a DOTAP liposome formulation containing a fusion protein (FP) containing Mycobacterium tuberculosis HspX, PPE44, and EsxV. METHODS: The FP was expressed in E. coli BL21 cells and confirmed by SDS-PAGE and Western blots. The FP was then encapsulated in various liposomal formulations. Afterwards, liposomal size, zeta potential, and encapsulation efficiency were evaluated. Mice were subcutaneously vaccinated on days 0, 14, and 28 with liposomes containing the FP. Two weeks after the last injection, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titers in sera were measured. RESULTS: The FP concentration was 1mg/ml. The encapsulation efficiency of the liposomes varied from 69% in Lip (DOTAP/TDB/CHOL/FP) to 80% in Lip (DOTAP/CHOL/FP). The greatest IFN-γ and IL-12 levels were observed in BCG-primed mice that were boosted with Lip (DOTAP/CHOL/FP). In addition, IL-17 production was significantly greater in all groups than controls except in those that received histidine buffer and FP. The IgG2a/IgG1 ratios were greater in the Lip (DOTAP/TDB/CHOL/FP), Lip (DOTAP/CHOL/FP), Lip (DOTAP/CHOL), and BCG-primed and Lip (DOTAP/CHOL/FP)-boosted groups than in the other groups, indicating a cellular immune response. CONCLUSION: The liposomes containing DOTAP combined with the fusion protein induced a Th1 response. The mice that first received BCG and then Lip (DOTAP/CHOL/FP), produced the most IFN-γ and IL-12, indicating a strong Th1 response.
BACKGROUND: Due to the ineffectiveness of the BCG vaccine, especially in adult pulmonary tuberculosis (TB), and variable efficacies against childhood forms of TB, developing an effective TB vaccine is a major priority in controlling this disease. The aim of this study was to evaluate the immunogenicity of a DOTAP liposome formulation containing a fusion protein (FP) containing Mycobacterium tuberculosis HspX, PPE44, and EsxV. METHODS: The FP was expressed in E. coli BL21 cells and confirmed by SDS-PAGE and Western blots. The FP was then encapsulated in various liposomal formulations. Afterwards, liposomal size, zeta potential, and encapsulation efficiency were evaluated. Mice were subcutaneously vaccinated on days 0, 14, and 28 with liposomes containing the FP. Two weeks after the last injection, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titers in sera were measured. RESULTS: The FP concentration was 1mg/ml. The encapsulation efficiency of the liposomes varied from 69% in Lip (DOTAP/TDB/CHOL/FP) to 80% in Lip (DOTAP/CHOL/FP). The greatest IFN-γ and IL-12 levels were observed in BCG-primed mice that were boosted with Lip (DOTAP/CHOL/FP). In addition, IL-17 production was significantly greater in all groups than controls except in those that received histidine buffer and FP. The IgG2a/IgG1 ratios were greater in the Lip (DOTAP/TDB/CHOL/FP), Lip (DOTAP/CHOL/FP), Lip (DOTAP/CHOL), and BCG-primed and Lip (DOTAP/CHOL/FP)-boosted groups than in the other groups, indicating a cellular immune response. CONCLUSION: The liposomes containing DOTAP combined with the fusion protein induced a Th1 response. The mice that first received BCG and then Lip (DOTAP/CHOL/FP), produced the most IFN-γ and IL-12, indicating a strong Th1 response.
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