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| Recombinant Plasmid pcDNA3-dnaJ Prime/DnaJ Protein Boost Immunization Induce Th1/Th17 Immune Responses and Protect Mice Against Pneumococcal Infection |
SUN Si1,QIU Yu-lan2,YAN Ju-rong1,YANG Jing1,WU Guang-ying1,WANG Lin1,XU Wen-chun1,**( ) |
1 Key Laboratory of Diagnostics Medicine Designated by the Chinese Ministry of Education,Chongqing Medical University, Chongqing 400016, China
2 Laboratory of Nuclear Medicine, Children’s Hospital of Chongqing Medical University, Chongqing 400016, China; |
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Abstract Objective: To explore more effective S. pneumoniae DNA vaccines and vaccine immunization strategies and explore their protective mechanisms.Methods: The recombinant plasmid pcDNA3-dnaJ was constructed and DnaJ protein was expressed. The recombinant plasmid pcDNA3-dnaJ/protein DnaJ immunized group and the plasmid pcDNA3-dnaJ immunized group were separately set to compare the nasal lavage of mice treated with S. pneumoniae strain. The bacterial load and survival rate of the liquid, serum antibody titer and inflammatory factors after challenged were measured by ELISA. The activation of BMDCs and the immune responses of Th1 and Th17 cells were analyzed by flow cytometry.Methods: The plasmid pcDNA3-dnaJ immunization three times induced antigen-specific antibody in serum and reduced the bacterial loads in the nasopharynx after challenge with live S. pneumoniae, but it was less effective in protecting against a lethal infection. However, compared with repeating the plasmid DNA innoculation three times, the strategy of pcDNA3-dnaJ prime one time/DnaJ protein boost one time could significantly reduce the pneumococcal colonization in the nasopharynx and provid better protection against lethal infection. Furthermore, DnaJ protein boosting generated higher levels of IFN-γ and IL-17A than the DNA boosting.Conclusion: Compared with DNA plasmid booster, immunization using DNA prime/protein boost of pneumococcus protein may be a new strategy to develop vaccines against pneumococcal infection.
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Received: 19 April 2019
Published: 15 January 2020
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Corresponding Authors:
Wen-chun XU
E-mail: xuwen@cqmu.edu.com
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| [1] |
O’Brien K L, Wolfson L J, Watt J P , et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet, 2009,374(9693):893-902
|
|
|
| [2] |
WHO. Pneumococcal vaccines WHO position paper--2012. Releve Epidemiologique Hebdomadaire, 2012,87(14):129-144.
|
|
|
| [3] |
Scott J A . The preventable burden of pneumococcal disease in the developing world. Vaccine, 2007,25(13):2398-2405.
|
|
|
| [4] |
Wang Y, Yue X, Jin H , et al. A suicidal DNA vaccine expressing the fusion protein of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in mice. J Virol Methods, 2015,225:35-40.
|
|
|
| [5] |
Li W, Wang S, Lu S . Pilot study on the use of DNA priming immunization to enhance Y. pestis LcrV-specific B cell responses elicited by a recombinant LcrV protein vaccine. Vaccines (Basel), 2013,2(1):36-48.
|
|
|
| [6] |
Li P, Cao R B, Zheng Q S , et al. Enhancement of humoral and cellular immunity in mice against Japanese encephalitis virus using a DNA prime-protein boost vaccine strategy. Vet J, 2010,183(2):210-216.
|
|
|
| [7] |
Golshani M, Rafati S, Siadat S D , et al. Improved immunogenicity and protective efficacy of a divalent DNA vaccine encoding Brucella L7/L12-truncated Omp31 fusion protein by a DNA priming and protein boosting regimen. Mol Immunol, 2015,66(2):384-391.
|
|
|
| [8] |
Wu K, Zhang X, Shi J , et al. Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae infections in mice. Infect Immun, 2010,78(3):1276-1283.
|
|
|
| [9] |
Nguyen C T, Kim S Y, Kim M S , et al. Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice. Vaccine, 2011,29(34):5731-5739.
|
|
|
| [10] |
Mann J F, Mckay P F, Arokiasamy S , et al. Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection. J Control Release, 2013,170(3):452-459.
|
|
|
| [11] |
Romani N, Gruner S, Brang D , et al. Proliferating dendritic cell progenitors in human blood. J Exp Med, 1994,180(1):83-93.
|
|
|
| [12] |
Sallusto F, Lanzavecchia A . Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med, 1994,179(4):1109-1118.
|
|
|
| [13] |
Kapsenberg M L . Dendritic-cell control of pathogen-driven T-cell polarization. Immunology, 2003,3(12):984-993.
|
|
|
| [14] |
Banchereau J, Steinman R M . Dendritic cells and the control of immunity. Nature, 1998,392(6673):245-252.
|
|
|
| [15] |
Kushwah R, Hu J . Complexity of dendritic cell subsets and their function in the host immune system. Immunology, 2011,133(4):409-419.
|
|
|
| [16] |
Schraml B U, Reis E, Sousa C . Defining dendritic cells. Curr Opin Immunol, 2015,32:13-20.
|
|
|
| [17] |
Guermonprez P, Valladeau J, Zitvogel L , et al. Antigen presentation and T cell stimulation by dendritic cells. Annual Review of Immunology, 2002,20(1):621-667.
|
|
|
| [18] |
Jonuleit H, Kuhn U, Muller G , et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol, 1997,27(12):3135-3142.
|
|
|
| [19] |
Grant E V, Thomas M, Fortune J , et al. Enhancement of plasmid DNA immunogenicity with linear polyethylenimine. Eur J Immunol, 2012,42(11):2937-2948.
|
|
|
| [20] |
Wegmann F, Gartlan K H, Harandi A M , et al. Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nat Biotechnol, 2012,30(9):883-888.
|
|
|
| [21] |
Mann J F, Mckay P F, Arokiasamy S , et al. Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection. J Control Release, 2013,170(3):452-459.
|
|
|
| [22] |
Lu Y J, Gross J, Bogaert D , et al. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog, 2008,4(9):e1000159.
|
|
|
| [23] |
Zhang Z, Clarke T B, Weiser J N . Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest, 2009,119(7):1899-1909.
|
|
|
| [24] |
Wang W, Zhou A, Zhang X , et al. Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media. Infect Immun, 2014,82(6):2368-2377.
|
|
|
| [25] |
Wilson R, Cohen J M, Jose R J , et al. Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses. Mucosal Immunol, 2015,8(3):627-639.
|
|
|
| [26] |
Blair C, Naclerio R M, Yu X , et al. Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model. J Infect Dis, 2005,192(7):1237-1244.
|
|
|
| [27] |
Jahn-Schmid B, Messner P, Unger F M , et al. Toward selective elicitation of TH1-controlled vaccination responses: vaccine applications of bacterial surface layer proteins. Journal of Biotechnology, 1996,44(1-3):225-231.
|
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