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http://dx.doi.org/10.4014/jmb.1707.07075

Humanized Mice for the Evaluation of Francisella tularensis Vaccine Candidates  

Oh, Hanseul (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Kim, C-Yoon (Department of Stem Cell Biology, School of Medicine, Konkuk University)
Kim, Chang-Hwan (The 5th R&D Institute-3, Agency for Defense Development)
Hur, Gyeung-Haeng (The 5th R&D Institute-3, Agency for Defense Development)
Lee, Ji Min (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Chang, Seo-Na (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Park, Jae-Hak (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Publication Information
Journal of Microbiology and Biotechnology / v.28, no.1, 2018 , pp. 157-164 More about this Journal
Abstract
Francisella tularensis (FT), a highly infectious pathogen, is considered to be a potential biological weapon owing to the current lack of a human vaccine against it. Tul4 and FopA, both outer membrane proteins of FT, play an important role in the bacterium's immunogenicity. In the present study, we evaluated the immune response of mice - humanized with human CD34+ cells (hu-mice) - to a cocktail of recombinant Tul4 and FopA (rTul4 and rFopA), which were codon-optimized and expressed in Escherichia coli. Not only did the cocktail-immunized hu-mice produce a significant human immunoglobulin response, they also exhibited prolonged survival against an attenuated live vaccine strain as well as human T cells in the spleen. These results suggest that the cocktail of rTul4 and rFopA had successfully induced an immune response in the hu-mice, demonstrating the potential of this mouse model for use in the evaluation of FT vaccine candidates.
Keywords
Francisella tularensis; humanized mice; vaccine;
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1 Huntley JF, Conley PG, Hagman KE, Norgard MV. 2007. Characterization of Francisella tularensis outer membrane proteins. J. Bacteriol. 189: 561-574.   DOI
2 Hickey AJ, Hazlett KR, Kirimanjeswara GS, Metzger DW. 2011. Identification of Francisella tularensis outer membrane protein A (FopA) as a protective antigen for tularemia. Vaccine 29: 6941-6947.
3 Sunagar R, Kumar S, Franz BJ, Gosselin EJ. 2016. Tularemia vaccine development: paralysis or progress? Vaccine (Auckl.) 6: 9-23.
4 Fritz DL, England MJ, Miller L, Waag DM. 2014. Mouse models of aerosol-acquired tularemia caused by Francisella tularensis types A and B. Comp. Med. 64: 341-350.
5 Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, et al. 2012. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492: 118-122.   DOI
6 Yajima M, Imadome K, Nakagawa A, Watanabe S, Terashima K, Nakamura H, et al. 2008. A new humanized mouse model of Epstein-Barr virus infection that reproduces persistent infection, lymphoproliferative disorder, and cellmediated and humoral immune responses. J. Infect. Dis. 198: 673-682.
7 Jaiswal S, Smith K, Ramirez A, Woda M, Pazoles P, Shultz LD, et al. 2015. Dengue virus infection induces broadly crossreactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. Exp. Biol. Med. (Maywood) 240: 67-78.
8 Oh H, Kim CY, Kim C H, Hur GH, Park JH. 2016. A synthetic Tul4 and FopA peptide cocktail of Francisella tularensis induces humoral and cell-mediated immune responses in mice. J. Microbiol. Biotechnol. 26: 1613-1619.   DOI
9 Baenziger S, Tussiwand R, Schlaepfer E, Mazzucchelli L, Heikenwalder M, Kurrer MO, et al. 2006. Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/- mice. Proc. Natl. Acad. Sci. USA 103: 15951-15956.   DOI
10 Cox J, Mota J, Sukupolvi-Petty S, Diamond MS, Rico-Hesse R. 2012. Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice. J. Virol. 86: 7637-7649.   DOI
11 Matsumura T, Kametani Y, Ando K, Hirano Y, Katano I, Ito R, et al. 2003. Functional CD5+ B cells develop predominantly in the spleen of NOD/SCID/gammac(null) (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells. Exp. Hematol. 31: 789-797.   DOI
12 Jangalwe S, Shultz LD, Mathew A, Brehm MA. 2016. Improved B cell development in humanized NOD-scid IL2Rgammanull mice transgenically expressing human stem cell factor, granulocyte-macrophage colony-stimulating factor and interleukin-3. Immun. Inflamm. Dis. 4: 427-440.
13 Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, et al. 2009. The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). Int. Immunol. 21: 843-858.   DOI
14 Vuyyuru R, Patton J, Manser T. 2011. Human immune system mice: current potential and limitations for translational research on human antibody responses. Immunol. Res. 51:257-266.   DOI
15 Chen Q, Khoury M , Chen J. 2009. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc. Natl. Acad. Sci. USA 106: 21783-21788.   DOI
16 Vartak A, Sucheck SJ. 2016. Recent Advances in Subunit Vaccine Carriers. Vaccines (Basel) 4: E12.   DOI
17 Cowley SC, Elkins KL. 2003. Multiple T cell subsets control Francisella tularensis LVS intracellular growth without stimulation through macrophage interferon gamma receptors. J. Exp. Med. 198: 379-389.   DOI
18 Oyston P C, S jostedt A, T itball RW. 2004. Tularaemia: bioterrorism defence renews interest in Francisella tularensis. Nat. Rev. Microbiol. 2: 967-978.   DOI
19 Katz L, Orr-Urteger A, Brenner B, Hourvitz A. 2002. [Tularemia as a biological weapon]. Harefuah 141 Spec No: 78-83, 120.
20 Gregory SH, Mott S, Phung J, Lee J, Moise L, McMurry JA, et al. 2009. Epitope-based vaccination against pneumonic tularemia. Vaccine 27: 5299-5306.   DOI
21 Ashtekar AR, Katz J, Xu Q, Michalek SM. 2012. A mucosal subunit vaccine protects against lethal respiratory infection with Francisella tularensis LVS. PLoS One 7: e50460.