Document Type : Original Research
Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
Applied Microbiology Research Center, Systems biology and poisonings institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Academy of Medical Sciences of the IR of Iran, Tehran, Iran
Background & Objective: Despite the vaccination with the BCG vaccine, tuberculosis (TB) remains one of the major health problems in the world. The aim of this study was to evaluate our newly designed vaccine using IL-22 as an adjuvant in comparison with the common BCG vaccine.
Methods: The gene constructs were cloned into the expression vector of pET28a and then into the recombinant vector of PET28a – HSPX, and PPE44 was transformed into Escherichia coli BL21 (DE3). Finally, the immunogenicity of recombinant proteins with and without BCG and IL-22 in BALB/c mice was investigated.
Results: The key cytokines INF-γ and TNF-α were elevated more greatly in BCG immunized group than in PHF immunized group.
Immunization with PHF showed a significant increase in IL-4 levels versus the BCG group. Adding IL-22 to the vaccine formulations indicated a tiny increase in IL-4 levels compared to their related vaccine groups.
Specific total IgG1 in the experimental groups showed an increase in comparison with control groups, but in the vaccinated groups, no significant differences were observed, and the presence of IL-22 in the vaccine formulations indicated a slight decrease compared with the related mere vaccine groups. Results of specific total IgG2a in the experimental groups revealed that only in the PHF group formulated with IL-22 a significant increase occurs compared with all other experimental groups.
Conclusion: It seems that BCG, as the only licensed vaccine for TB infection, could be more potent than a recombinant vaccine in the induction of cellular and humoral immune responses.
- Gicquel B. Towards new mycobacterial vaccines. Dev Biol Stand. 1994;82:171-8.
- Lawn SD. Alimuddin. Tuberculosis Lancet. 2011;378:57-72. [DOI:10.1016/S0140-6736(10)62173-3]
- Dara M, Dadu A, Kremer K, Zaleskis R, Kluge HH. Epidemiology of tuberculosis in WHO European Region and public health response. Eur Spine J. 2013;22 Suppl 4(4):549-55. [PMCID] [DOI:10.1007/s00586-012-2339-3] [PMID]
- Saini D, Hopkins GW, Seay SA, Chen CJ, Perley CC, Click EM, et al. Ultra-low dose of Mycobacterium tuberculosis aerosol creates partial infection in mice. Tuberculosis (Edinb). 2012;92(2):160-5. [PMID] [PMCID] [DOI:10.1016/j.tube.2011.11.007]
- Delogu G, Fadda G. The quest for a new vaccine against tuberculosis. J Infect Dev Ctries. 2009;3(1):5-15. [DOI:10.3855/jidc.99] [PMID]
- Organization WH. Global tuberculosis control: epidemiology, strategy, financing: WHO report 2009: World Health Organization; 2009.
- Yuan W, Dong N, Zhang L, Liu J, Lin S, Xiang Z, et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine expressing a fusion protein of Ag85B-Esat6-HspX in mice. Vaccine. 2012;30(14):2490-7. [DOI:10.1016/j.vaccine.2011.06.029] [PMID]
- Jeon BY, Kim SC, Eum SY, Cho SN. The immunity and protective effects of antigen 85A and heat-shock protein X against progressive tuberculosis. Microbes Infect. 2011;13(3):284-90. [DOI:10.1016/j.micinf.2010.11.002] [PMID]
- Romano M, Aryan E, Korf H, Bruffaerts N, Franken C, Ottenhoff T, et al. Potential of Mycobacterium tuberculosis resuscitation-promoting factors as antigens in novel tuberculosis sub-unit vaccines. Microb Infect. 2012;14(1):86-95. [DOI:10.1016/j.micinf.2011.08.011] [PMID]
- Tyagi AK, Nangpal P, Satchidanandam V. Development of vaccines against tuberculosis. Tuberculosis (Edinb). 2011;91(5):469-78. [DOI:10.1016/j.tube.2011.01.003] [PMID]
- Bruffaerts N, Romano M, Denis O, Jurion F, Huygen K. Increasing the Vaccine Potential of Live M. bovis BCG by Coadministration with Plasmid DNA Encoding a Tuberculosis Prototype Antigen. Vaccines (Basel). 2014;2(1):181-95. [DOI:10.3390/vaccines2010181] [PMID] [PMCID]
- Lowrie DB, Silva CL, Tascon RE. DNA vaccines against tuberculosis. Immunol Cell Biol. 1997;75(6):591-4. [DOI:10.1038/icb.1997.93] [PMID]
- Lowrie DB, Tascon RE, Bonato VL, Lima VM, Faccioli LH, Stavropoulos E, et al. Therapy of tuberculosis in mice by DNA vaccination. Nature. 1999;400(6741):269-71. [DOI:10.1038/22326] [PMID]
- Okuda K, Wada Y, Shimada M. Recent Developments in Preclinical DNA Vaccination. Vaccines (Basel). 2014;2(1):89-106. [PMCID] [DOI:10.3390/vaccines2010089] [PMID]
- Mustafa AS. Biotechnology in the development of new vaccines and diagnostic reagents against tuberculosis. Curr Pharm Biotechnol. 2001;2(2): 157-73. [DOI:10.2174/1389201013378707] [PMID]
- Kaufmann SH. Fact and fiction in tuberculosis vaccine research: 10 years later. Lancet Infect Dis. 2011;11(8):633-40. [DOI:10.1016/S1473-3099(11)70146-3]
- Cuccu B, Freer G, Genovesi A, Garzelli C, Rindi L. Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44. BMC Microbiol. 2011;11(1):167. [DOI:10.1186/1471-2180-11-167] [PMID] [PMCID]
- Liu W, Li J, Niu H, Lin X, Li R, Wang Y, et al. Immunogenicity and protective efficacy of multistage vaccine candidates (Mtb8.4-HspX and HspX-Mtb8.4) against Mycobacterium tuberculosis infection in mice. Int Immuno-pharmacol. 2017;53:83-9. [DOI:10.1016/j.intimp.2017.10.015] [PMID]
- Soleimanpour S, Farsiani H, Mosavat A, Ghazvini K, Eydgahi MR, Sankian M, et al. APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice. Appl Microbiol Biotechnol. 2015;99(24):10467-80. [DOI:10.1007/s00253-015-6952-z] [PMID]
- Kaur G, Chitradevi S, Nimker C, Bansal A. rIL-22 as an adjuvant enhances the immunogenicity of rGroEL in mice and its protective efficacy against S. Typhi and S. Typhimurium. Cell Molecul Immunol. 2015;12(1):96-106. [DOI:10.1038/cmi.2014.34] [PMID] [PMCID]
- Wu B, Zou Q, Hu Y, Wang B. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice. Hum Vaccines Immunother. 2013;9(10):2133-41. [DOI:10.4161/hv.26047] [PMID] [PMCID]
- Hezarjaribi HZ, Ghaffarifar F, Dalimi A, Sharifi Z, Jorjani O. Effect of IL-22 on DNA vaccine encoding LACK gene of Leishmania major in BALB/c mice. Exp Parasitol. 2013;134(3):341-8. [DOI:10.1016/j.exppara.2013.03.012] [PMID]
- Bhatt K, Salgame P. Host innate immune response to Mycobacterium tuberculosis. J Clin Immunol. 2007;27(4):347-62. [DOI:10.1007/s10875-007-9084-0] [PMID]
- Bonanni D, Rindi L, Lari N, Garzelli C. Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice. J Med Microbiol. 2005;54(Pt 5):443-8. [DOI:10.1099/jmm.0.45960-0] [PMID]
- Romano M, Rindi L, Korf H, Bonanni D, Adnet PY, Jurion F, et al. Immunogenicity and protective efficacy of tuberculosis subunit vaccines expressing PPE44 (Rv2770c). Vaccine. 2008;26(48):6053-63. [DOI:10.1016/j.vaccine.2008.09.025] [PMID]
- Rindi L, Peroni I, Lari N, Bonanni D, Tortoli E, Garzelli C. Variation of the expression of Mycobacterium tuberculosis ppe44 gene among clinical isolates. Immunol Med Microbiol. 2007;51(2):381-7. [DOI:10.1111/j.1574-695X.2007.00315.x] [PMID]
- Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science. 1999;284(5419):1520-3. [DOI:10.1126/science.284.5419.1520] [PMID]
- Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. Jama. 1994;271(9):698-702. [PMID] [DOI:10.1001/jama.1994.03510330076038]
- McMurry J, Sbai H, Gennaro ML, Carter EJ, Martin W, De Groot AS. Analyzing Mycobacterium tuberculosis proteomes for candidate vaccine epitopes. Tuberculosis (Edinb). 2005;85(1-2):95-105. [DOI:10.1016/j.tube.2004.09.005] [PMID]
- Shi C, Chen L, Chen Z, Zhang Y, Zhou Z, Lu J, et al. Enhanced protection against tuberculosis by vaccination with recombinant BCG over-expressing HspX protein. Vaccine. 2010;28(32): 5237-44. [DOI:10.1016/j.vaccine.2010.05.063] [PMID]
- Kumar A, Toledo JC, Patel RP, Lancaster JR, Steyn AJ. Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci. 2007;104(28):11568-73. [PMCID] [DOI:10.1073/pnas.0705054104] [PMID]
- Baghani AA, Soleimanpour S, Farsiani H, Mosavat A, Yousefi M, Meshkat Z, et al. CFP10: mFcgamma2 as a novel tuberculosis vaccine candidate increases immune response in mouse. Iran J Basic Med Sci. 2017;20(2):122-30.
- Farsiani H, Mosavat A, Soleimanpour S, Sadeghian H, Akbari Eydgahi MR, Ghazvini K, et al. Fc-based delivery system enhances immunogenicity of a tuberculosis subunit vaccine candidate consisting of the ESAT-6:CFP-10 complex. Mol Biosyst. 2016;12(7):2189-201. [DOI:10.1039/C6MB00174B] [PMID]
- Probst HC, Lagnel J, Kollias G, van den Broek M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity. 2003;18(5):713-20. [DOI:10.1016/S1074-7613(03)00120-1]
- Moradi B, Sankian M, Amini Y, Meshkat Z. Construction of a Novel DNA Vaccine Candidate Encoding an HspX-PPE44-EsxV Fusion Antigen of Mycobacterium tuberculosis. Rep Biochem Mol Biol. 2016;4(2):89-97.
- Mekhaiel DN, Czajkowsky DM, Andersen JT, Shi J, El-Faham M, Doenhoff M, et al. Polymeric human Fc-fusion proteins with modified effector functions. Sci Rep. 2011;1:124. [DOI:10.1038/srep00124] [PMID] [PMCID]
- Konduru K, Bradfute SB, Jacques J, Manangeeswaran M, Nakamura S, Morshed S, et al. Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice. Vaccine. 2011;29(16):2968-77. [DOI:10.1016/j.vaccine.2011.01.113] [PMID] [PMCID]
- Loureiro S, Ren J, Phapugrangkul P, Colaco CA, Bailey CR, Shelton H, et al. Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach to influenza vaccines. J Virol. 2011;85(6):3010-4. [DOI:10.1128/JVI.01241-10] [PMID] [PMCID]
- Lu L, Palaniyandi S, Zeng R, Bai Y, Liu X, Wang Y, et al. A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV-1 antigen-specific immunity to genital infection. J Virol. 2011;85(20):10542-53. [DOI:10.1128/JVI.05441-11] [PMID] [PMCID]
- Quesniaux VF, Jacobs M, Allie N, Grivennikov S, Nedospasov SA, Garcia I, et al. TNF in host resistance to tuberculosis infection. TNF Pathophysiology. 11: Karger Publishers; 2010. p. 157-79. [DOI:10.1159/000289204] [PMID]
- Kaur G, Sts C, Nimker C, Singh M, Saraswat D, Saxena S, et al. Co-expression of S. Typhi GroEL and IL-22 gene augments immune responses against Salmonella infection. Immunol Cell Biol. 2013;91(10):642-51. [DOI:10.1038/icb.2013.61] [PMID]