Recombinant AhpC antigen from Mycobacterium bovis boosts BCG-primed immunity in mice

Recombinant AhpC antigen from Mycobacterium bovis boosts BCG-primed immunity in mice

Tuberculosis (TB) is still one of the most common infectious diseases around the world despite the widespread use of BCG (bacille Calmette-Guerin) strain of Mycobacterium bovis as a vaccine. This vaccine does not always protect people from TB, and, thus, new effective vaccines or vaccination strategies are being investigated. In this study, alkyl hydroperoxide reductase (AhpC) from M. bovis was evaluated as a new candidate vaccine antigen against TB in BALB/c mice model. The ahpC gene was amplified from M.bovis genome, cloned, and expressed in Escherichia coli. Vaccine antigen AhpC was formulated with Montanide ISA 61 VG, an oil-based emulsion adjuvant. Both IgG and IL-12 responses were observed in mice after administering the formulation both as a subunit vaccine alone and also as a booster vaccine for BCG immunization. However, a long-lasting response was observed when AhpC formulation was used as a booster (for BCG-primed immunization) as compared to being used as a subunit vaccine alone. In short, these findings suggested that AhpC has the potential to be used as a booster vaccine candidate for BCG-primed immunization.

___

  • Begg DJ, Dhungyel O, Naddi A, Dhand NK, Plain KM et al. (2019). The immunogenicity and tissue reactivity of Mycobacterium avium subsp paratuberculosis inactivated whole cell vaccine is dependent on the adjuvant used. Heliyon 5: e01911. doi: 10.1016/j.heliyon.2019.e01911
  • Bradford MM (1976). A rapid and sensitive method for the quantitation of microgramquantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72: 248-254. doi: 10.1016/0003-2697(76)90527-3
  • Chauhan R, Mande SC (2002). Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C. Biochemical Journal 367 (1): 255-261. doi: 10.1042/bj20020545
  • Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E et al. (1994). Efficacy of BCG vaccine in the prevention of tuberculosis: Meta-analysis of the published literature. JAMA. 271 (9): 698-702. doi:10.1001/jama.1994.03510330076038
  • Dalmia N, Ramsay AJ (2012). Prime-boost approaches to tuberculosis vaccine development. Expert Review of Vaccines 11 (10): 1221- 1233. doi: 10.1586/erv.12.94.
  • Echeverria-Valencia G, Flores-Villalva S, Espitia CI (2018). Virulence factors and pathogenicity of Mycobacterium. In: Ribón W (editor). Mycobacterium - Research and Development. London: United Kigdom: InTech, pp. 231– 255.
  • Evans JT, Smith EG, Banerjee A, Smith RMM, Dale J et al. (2007). Cluster of human tuberculosis caused by Mycobacterium bovis: evidence for person-to-person transmission in the UK. The Lancet 369: 1270-1276. doi: 10.1016/S0140-6736(07)60598-4
  • Fatima S, Kumari A, Das G, Dwivedi VP (2020). Tuberculosis vaccine: A journey from BCG to present. Life Sciences 252: 117594. doi: 10.1016/j.lfs.2020.117594
  • Forrellad MA, Klepp LI, Gioffré A, y García JS, Morbidoni HR et al. (2013). Virulence factors of the Mycobacterium tuberculosis complex. Virulence 4 (1): 3-66. doi: 10.4161/ viru.22329
  • Grange JM (2001). Mycobacterium bovis infection in human beings. Tuberculosis 81 (1/2): 71-77. doi: 10.1054/tube.2000.0263
  • Hansson M, Nygren PA, Stahl S (2000). Design and production of recombinant subunit vaccines. Biotechnology and Applied Biochemistry 32 (2): 95-107. doi: 10.1042/BA20000034
  • Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, de Montellano PRO (2000). The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. Journal of Biological Chemistry 275 (25): 18801–18809. doi: 10.1074/jbc.M001001200
  • Ibrahim El-SE, Gamal WM, Hassan AI, Mahdy SEl-D, Hegazy AZ et al. (2015). Comparative study on the immunopotentiator effect of ISA 201, ISA 61, ISA 50, ISA 206 used in trivalent foot and mouth disease vaccine. Veterinary World 8 (10): 1189-1198. doi: 10.14202/vetworld.2015.1189-1198
  • Galipeau Y, Greig M, Liu G, Driedger M, Langlois MA (2020). Humoral Responses and Serological Assays in SARS-CoV-2 Infections. Frontiers in Immunology 11: 610688. doi: 10.3389/ fimmu.2020.610688
  • Iz SG, Sağlam Metiner P, Kımız I, Kayalı Ç, Deliloğlu Gürhan SI (2018). Polyclonal antibody production against hapten-structured KDN molecule by using different adjuvants alternative to freund’s adjuvant. European Journal of Therapeutics 24 (2): 106-111. doi: 10.5152/EurJTher.2018.400
  • Jang SI, Lillehoj HS, Lee SH, Lee KW, Park MS et al. (2010). Immunoenhancing effects of Montanide ISA oil-based adjuvants on recombinant coccidia antigen vaccination against Eimeria acervulina infection. Veterinary Parasitology 172: 221–228. doi: 10.1016/j.vetpar.2010.04.042
  • Kanipe C, Palmer MV (2020). Mycobacterium bovis and you: A comprehensive look at the bacteria, its similarities to Mycobacterium tuberculosis, and its relationship with human disease. Tuberculosis 125: 102006. doi: 10.1016/j. tube.2020.102006
  • Kaufmann SHE, Parida SK (2008). Tuberculosis in Africa: learning from pathogenesis for biomarker identification. Cell Host & Microbe 4 (3): 219-228. doi: 10.1016/j.chom.2008.08.002
  • Khorasani A, Madadgar O, Soleimanjahi H, Keyvanfar H, Mahravani H (2016). Evaluation of the efficacy of a new oil-based adjuvant ISA 61 VG FMD vaccine as a potential vaccine for cattle. Iranian Journal of Veterinary Research 17 (1): 8-12.
  • Laemmli UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227 (5259): 680-685. doi: 10.1038/227680a0
  • Leroux-Roels G (2010). Unmet needs in modern vaccinology: Adjuvants to improve the immune response. Vaccine. 28: C25-C36. doi: 10.1016/j.vaccine.2010.07.021
  • McCutcheon SR, Chiu KL, Lewis DD, Tan C (2018). CRISPR-Cas Expands Dynamic Range of Gene Expression From T7RNAP Promoters. Biotechnology Journal 13 (5): e1700167. doi: 10.1002/biot.201700167
  • Michel AL, Müller B, van Helden PD (2010). Mycobacterium bovis at the animal–human interface: A problem, or not? Veterinary Microbiology 140 (3-4): 371-381. doi: 10.1016/j. vetmic.2009.08.029
  • Okay S, Özcengiz E, Gürsel I, Özcengiz G (2012). Immunogenicity and protective efficacy of the recombinant Pasteurella lipoprotein E and outer membrane protein H from Pasteurella multocida A: 3 in mice. Research in Veterinary Science 93 (3): 1261-1265. doi: 10.1016/j.rvsc.2012.05.011
  • O’Riordan AA, Morales VA, Mulligan L, Faheem N, Windle HJ et al. (2012). Alkyl hydroperoxide reductase: A candidate Helicobacter pylori vaccine. Vaccine 30 (26): 3876-3884. doi:10.1016/j.vaccine.2012.04.002
  • Rodriguez-Campos S, Smith NH, Boniotti MB, Aranaz A (2014). Overview and phylogeny of Mycobacterium tuberculosis complex organisms: Implications for diagnostics and legislation of bovine tuberculosis. Research in Veterinary Science 97: S5- S19. doi: 10.1016/j.rvsc.2014.02.009
  • Seppic (2017). MontanideTM.https://www.seppic.com/sites/seppic/ files/2017/02/28/seppic-montanide.pdf(accessed 10 February 2021).
  • Shah RR, Brito LA, O’Hagan DT, Amiji MM (2015). Emulsions as Vaccine Adjuvants. In: Foged C, Rades T, Perrie Y, Hook S (editors). Subunit Vaccine Delivery. Springer, New York: pp. 59-76.
  • Sunder S, Lanotte P, Godreuil S, Martin C, Boschiroli M et al. (2009). Human-to-human transmission of tuberculosis caused by Mycobacterium bovis in immunocompetent patients. Journal of Clinical Microbiology 47 (4): 1249-1251. doi: 10.1128/ JCM.02042-08
  • Towbin H, Staehelin T, Gordon J (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences 76 (9): 4350-4354. doi: 10.1073/ pnas.76.9.4350
  • Valdés I, Lazo L, Hermida L, Guillén G, Gil L (2019). Can Complementary Prime-Boost Immunization Strategies Be an Alternative and Promising Vaccine Approach Against Dengue Virus? Frontiers in Immunology 10: 1956. doi: 10.3389/ fimmu.2019.01956
  • Verma H, Nagar S, Vohra S, Pandey S, Lal D et al. (2021). Genome analyses of 174 strains of Mycobacterium tuberculosis provide insight into the evolution of drug resistance and reveal potential drug targets. Microbial Genomics 7 (3): 000542. doi: 10.1099/ mgen.0.000542
  • Whitlow E, Mustafa AS, Hanif, SNM (2020). An overview of the development of new vaccines for tuberculosis. Vaccines 8 (4): 586. doi: 10.3390/vaccines8040586
  • Wilson T, de Lisle GW, Marcinkeviciene JA, Blanchard JS, Collins DM (1998). Antisense RNA to ahpC, an oxidative stress defence gene involved in isoniazid resistance, indicates that AhpC of Mycobacterium bovis has virulence properties. Microbiology 144 (10): 2687-2695. 10.1099/00221287-144-10-2687
  • Wilson TM, Collins DM (1996). ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex. Molecular Microbiology 19 (5): 1025-1034. doi: 10.1046/j.1365- 2958.1996.449980.x
  • Wong CF, Shin J, Manimekalai MSS, Saw WG, Yin Z et al. (2017). AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C. Scientific Reports 7: 5159. doi: 10.1038/s41598-017-05354-5
  • World Health Organization (2020). Global Tuberculosis Report 2020. Geneva: World Health Organization: Licence: CC BYNC-SA 3.0 IGO.
  • Yang E, Gu J, Wang F, Wang H, Shen H et al. (2016). Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice. Microbial Pathogenesis 93: 1-7.