323
Views
14
CrossRef citations to date
0
Altmetric
Review

Progress, challenges, and opportunities in Francisella vaccine development

, &
Pages 1183-1196 | Received 29 Jan 2016, Accepted 22 Mar 2016, Published online: 03 May 2016

References

  • Mccoy G, Chapin CV. Bacterium tularense - the cause of a plague-like disease of rodents. Public Health Bulletin. 1912;53:17–23.
  • Francis E. Tularemia. J Am Med Assoc. 1925;84:1243–1250.
  • Keim P, Johansson A, Wagner DM. Molecular epidemiology, evolution, and ecology of Francisella. Ann N Y Acad Sci. 2007;1105:30–66.
  • Lyons CR, Wu TH. Animal models of Francisella tularensis infection. Ann N Y Acad Sci. 2007;1105:238–265.
  • Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health management. JAMA. 2001;285(21):2763–2773.
  • Pavlov VM, Kozlova II, Mokrievich AN, et al. Analysis of Francisella tularensis strains isolated from humans and small rodents during year 2013 tularemia outbreak in Khanty-mansiysk, West Siberia. Presented at: 8th International Conference on Tularemia; 2015 Sep; Opatija, Croatia.
  • Akalin H, Helvaci S, Gedikoglu S. Re-emergence of tularemia in Turkey. Int J Infect Dis. 2009;13(5):547–551.
  • Cowley SC, Elkins KL. Immunity to Francisella. Front Microbiol. 2011;2:26.
  • Elkins KL, Cowley SC, Bosio CM. Innate and adaptive immunity to Francisella. Ann N Y Acad Sci. 2007;1105:284–324.
  • Elkins KL, Cowley SC, Bosio CM. Innate and adaptive immune responses to an intracellular bacterium, Francisella tularensis Live Vaccine Strain. Microbes Infect. 2003;5:135–142.
  • Tärnvik A. Nature of protective immunity to Francisella tularensis. Rev Infect Dis. 1989;11:440–451.
  • Conlan JW, Oyston PCF. Vaccines against Francisella tularensis. Ann N Y Acad Sci. 2007;1105:325–350.
  • Sandström G, Sjöstedt A, Forsman M, et al. Characterization and classification of strains of Francisella tularensis isolated in the central asian focus of the Soviet Union and in Japan. J Clin Microbiol. 1992;30:172–175.
  • Ellis J, Oyston PCF, Green M, et al. Tularemia. Clin Microbiol Rev. 2002;15(4):631–646.
  • Staples JE, Kubota KA, Chalcraft LG, et al. Epidemiologic and molecular analysis of human tularemia, United States, 1964–2004. Emerg Infect Dis. 2006;12(7):1113–1118.
  • Petersen JM, Molins CR. Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. Future Microbiol. 2010;5(4):649–661.
  • Kugeler KJ, Mead PS, Janusz AM, et al. Molecular epidemiology of Francisella tularensis in the United States. Clin Infect Dis. 2009;48(7):863–870.
  • Bröms JE, Sjöstedt A, Lavander M. The role of the Francisella tularensis pathogenicity island in Type VI secretion, intracellular survival, and modulation of host cell signaling. Front Microbiol. 2010;1:136.
  • Jones BD, Faron M, Rasmussen JA, et al. Uncovering the components of the Francisella tularensis virulence stealth strategy. Front Cell Infect Microbiol. 2014;4:32.
  • Celli J, Zahrt TC. Mechanisms of Francisella tularensis intracellular pathogenesis. Cold Spring Harb Perspect Med. 2013;3(4):a010314.
  • Gunn JS, Ernst RK. The structure and function of Francisella lipopolysaccharide. Ann N Y Acad Sci. 2007;1105:202–218.
  • Nano FE, Schmerk C. The Francisella pathogenicity island. Ann N Y Acad Sci. 2007;1105:122–137.
  • Nano FE, Zhang N, Cowley SC, et al. A Francisella tularensis pathogenicity island required for intramacrophage growth. J Bacteriol. 2004;186(19):6430–6436.
  • Bosio CM, Bielefeldt-Ohmann H, Belisle JT. Active suppression of the pulmonary immune response by Francisella tularensis Schu4. J Immunol. 2007;178(7):4538–4547.
  • Gillette DD, Curry HM, Cremer T, et al. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes. Front Cell Infect Microbiol. 2014;4:45.
  • Cowley SC, Myltseva SV, Nano FE. Phase variation in Francisella tularensis affecting intracellular growth, lipopolysaccharide antigenicity, and nitric oxide production. Mol Microbiol. 1996;20:867–874.
  • Eigelsbach HT, Downs CM. Prophylactic effectiveness of live and killed tularemia vaccines. I. Production of vaccine and evaluation in the white mouse and guinea pig. J Immunol. 1961;87:415–425.
  • Waag DM, Galloway A, Sändstrom G, et al. Cell-mediated and humoral immune responses induced by scarification vaccination of human volunteers with a new lot of the Live Vaccine Strain of Francisella tularensis. J Clin Microbiol. 1992;30(9):2256–2264.
  • Conlan JW. Tularemia vaccines: recent developments and remaining hurdles. Future Microbiol. 2011;6:391–405.
  • Tigertt WD. Soviet viable Pasteurella tularensis vaccines. A review of selected articles. Bacteriol Rev. 1962;26:354–373.
  • Feodorova VA, Sayapina LV, Corbel MJ, et al. Russian vaccines against especially dangerous bacterial pathogens. Emerg Microbes Infect. 2014;3(12):e86.
  • Sändstrom G. The tularemia vaccine. J Chem Tech Biotechnol. 1994;59:315–320.
  • Eigelsbach HT, Hornick RB, Tulis JJ. Recent studies on live tularemia vaccine. Med Ann Dist Columbia. 1967;36(5):282–286.
  • Eigelsbach HT, Tulis JJ, Mcgavran MH, et al. Live tularemia vaccine. I. Host-parasite relationship in monkeys vaccinated intracutaneously or aerogenically. J Bacteriol. 1962;84:1020–1027.
  • National Research Council. Protecting the frontline in biodefense research: the special immunizations program. Washington (DC): The National Academies Press; 2011.
  • Pasetti MF, Cuberos L, Horn TL, et al. An improved Francisella tularensis Live Vaccine Strain (LVS) is well tolerated and highly immunogenic when administered to rabbits in escalating doses using various immunization routes. Vaccine. 2008;26(14):1773–1785.
  • El Sahly HM, Atmar RL, Patel SM, et al. Safety, reactogenicity and immunogenicity of Francisella tularensis Live Vaccine Strain in humans. Vaccine. 2009;27(36):4905–4911.
  • Hornick RB, Eigelsbach HT. Aerogenic immunization of man with live tularemia vaccine. Bacteriol Rev. 1966;30(3):532–538.
  • Saslaw S, Eigelsbach HT, Prior JA, et al. Tularemia vaccine study. II. Respiratory challenge. Arch Intern Med. 1961;107:134–146.
  • Mccrumb FR. Aerosol infection of man with Pasteurella tularensis. Bacteriol Rev. 1961;25:262–267.
  • Petrosino JF, Xiang Q, Karpathy SE, et al. Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence. J Bacteriol. 2006;188(19):6977–6985.
  • Rohmer L, Fong C, Abmayr S, et al. Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains. Genome Biol. 2007;8(6):R102.
  • Salomonsson E, Kuoppa K, Forslund A-L, et al. Reintroduction of two deleted virulence loci restores full virulence to the Live Vaccine Strain of Francisella tularensis. Infect Immun. 2009;77(8):3424–3431.
  • Marohn ME, Barry EM. Live attenuated tularemia vaccines: recent developments and future goals. Vaccine. 2013;31(35):3485–3491.
  • Burke DS. Immunization against tularemia: analysis of the effectiveness of live Francisella tularensis vaccine in prevention of laboratory-acquired tularemia. J Infect Dis. 1977;135:55–60.
  • Rusnak JM, Kortepeter MG, Hawley RJ, et al. Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecur Bioterror. 2004;2(4):281–293.
  • Fulton KM, Zhao X, Petit MD, et al. Immunoproteomic analysis of the human antibody response to natural tularemia infection with Type A or Type B strains or LVS vaccination. Int J Med Microbiol. 2011;301(7):591–601.
  • Chu P, Cunningham AL, Yu J-J, et al. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates. PLoS Pathog. 2014;10(10):e1004439.
  • Saslaw S, Eigelsbach HT, Wilson HE, et al. Tularemia vaccine study. I. Intracutaneous challenge. Arch Intern Med. 1961;107:121–133.
  • Ericsson M, Sandström G, Sjöstedt A, et al. Persistence of cell-mediated immunity and decline of humoral immunity to the intracellular bacterium Francisella tularensis 25 years after natural infection. J Infect Dis. 1994;170:110–114.
  • Eneslätt K, Rietz C, Rydén P, et al. Persistence of cell-mediated immunity three decades after vaccination with the Live Vaccine Strain of Francisella tularensis. Eur J Immunol. 2011;41(4):974–980.
  • Gries DM, Fairchok MP. Typhoidal tularemia in a human immunodeficiency virus-infected adolescent. Pediatr Infect Dis J. 1996;15(9):838–840.
  • Karttunen R, Surcel HM, Andersson G, et al. Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings. J Clin Microbiol. 1991;29(4):753–756.
  • Eneslätt K, Normark M, Björk R, et al. Signatures of T cells as correlates of immunity to Francisella tularensis. PLoS One. 2012;7(3):e32367.
  • Reed DS, Smith LP, Cole KS, et al. Live attenuated mutants of Francisella tularensis protect rabbits against aerosol challenge with a virulent type A strain. Infect Immun. 2014;82(5):2098–2105.
  • Eigelsbach HT, Tulis JJ, Overholt EL, et al. Aerogenic immunization of the monkey and guinea pig with live tularemia vaccine. Proc Soc Exp Biol Med. 1961;108:732–734.
  • Tulis JJ, Eigelsbach HT, Kerpsack RW. Host-parasite relationship in monkeys administered live tularemia vaccine. Am J Pathol. 1970;58(2):329–336.
  • Mcgavran MH, White JD, Eigelsbach HT, et al. Morphologic and immunohistochemical studies of the pathogenesis of infection and antibody formation subsequent to vaccination of Macaca irus with an attenuated strain of Pasteurella tularensis: I. Intracutaneous vaccination. Am J Pathol. 1962;41(3):259–271.
  • White JD, Mcgavran MH, Prickett PA, et al. Morphologic and immunohistochemical studies of the pathogenesis of infection and antibody formation subsequent to vaccination of Macaca irus with an attenuated strain of Pasteurella tularensis: II. Aerogenic vaccination. Am J Pathol. 1962;41(4):405–413.
  • Day WC, Berendt RF. Experimental tularemia in Macaca mulatta: relationship of aerosol particle size to the infectivity of airborne Pasteurella tularensis. Infect Immun. 1972;5(1):77–82.
  • Eigelsbach HT, Saslaw S, Tulis JJ, et al. Tularemia: the monkey as a model for man. San Antonio (TX): Southwestern Foundation for Research and Education; 1968.
  • Nelson M, Lever MS, Dean RE, et al. Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus). J Med Microbiol. 2010;59(Pt 9):1107–1113.
  • Nelson M, Lever MS, Savage VL, et al. Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus). Int J Exp Pathol. 2009;90(2):109–118.
  • Glynn AR, Alves DA, Frick O, et al. Comparison of experimental respiratory tularemia in three nonhuman primate species. Comp Immunol Microbiol Infect Dis. 2015;39:13–24.
  • Tulis JJ, Eigelsbach HT, Hornick RB. Oral vaccination against tularemia in the monkeys. Proc Soc Exp Biol Med. 1969;132(3):893–897.
  • Ray HJ, Chu P, Wu TH, et al. The Fischer 344 rat reflects human susceptibility to Francisella pulmonary challenge and provides a new platform for virulence and protection studies. PLoS One. 2010;5(4):e9952.
  • Wu TH, Zsemlye JL, Statom GL, et al. Vaccination of Fischer 344 rats against pulmonary infections by Francisella tularensis type A strains. Vaccine. 2009;27(34):4684–4693.
  • Cunningham AL, Dang KM, Yu J-J, et al. Enhancement of vaccine efficacy by expression of a TLR5 ligand in the defined live attenuated Francisella tularensis subsp. novicida strain U112ΔiglB:: fljB. Vaccine. 2014;32(40):5234–5240.
  • Mara-Koosham G, Hutt JA, Lyons CR, et al. Antibodies contribute to effective vaccination against respiratory infection by type A Francisella tularensis strains. Infect Immun. 2011;79(4):1770–1778.
  • Conlan JW, Chen W, Bosio CM, et al. Infection of mice with Francisella as an immunological model. Curr Protoc Immunol. 2011;93:19.14.11–19.14.16.
  • Chen W, Shen H, Webb A, et al. Tularemia in BALB/c and C57BL/6 mice vaccinated with Francisella tularensis LVS and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background. Vaccine. 2003;21(25–26):3690–3700.
  • Cole LE, Yang Y, Elkins KL, et al. Antigen-specific B-1a antibodies induced by Francisella tularensis LPS provide long-term protection against F. tularensis LVS challenge. Proc Natl Acad Sci U S A. 2009;106(11):4343–4348.
  • Twine SM, Petit MD, Shen H, et al. Immunoproteomic analysis of the murine antibody response to successful and failed immunization with live anti-Francisella vaccines. Biochem Biophys Res Commun. 2006;346(3):999–1008.
  • Lavine CL, Clinton SR, Angelova-Fischer I, et al. Immunization with heat-killed Francisella tularensis LVS elicits protective antibody-mediated immunity. Eur J Immunol. 2007;37(11):3007–3020.
  • De Pascalis R, Mittereder L, Chou AY, et al. Francisella tularensis vaccines elicit concurrent protective T- and B-cell immune responses in BALB/cByJ mice. PLoS One. 2015;10(5):e0126570.
  • Elkins KL, Bosio CM, Rhinehart-Jones TR. Importance of B cells, but not specific antibodies, in primary and secondary protective immunity to the intracellular bacterium Francisella tularensis Live Vaccine Strain. Infect Immun. 1999;67:6002–6007.
  • Conlan JW, Sjöstedt A, North RJ. CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice. Infect Immun. 1994;62:5603–5607.
  • Griffin AJ, Crane DD, Wehrly TD, et al. Successful protection against tularemia in C57BL/6 mice is correlated with expansion of Francisella tularensis-specific effector T cells. Clin Vaccine Immunol. 2015;22(1):119–128.
  • Cowley SC, Elkins KL. Multiple T cell subsets control Francisella tularensis LVS intracellular growth without stimulation through macrophage interferon gamma receptors. J Exp Med. 2003;198(3):379–389.
  • Cowley SC, Hamilton E, Frelinger JA, et al. CD4−CD8− T cells control intracellular bacterial infections both in vitro and in vivo. J Exp Med. 2005;202(2):309–319.
  • Cowley SC, Meierovics AI, Frelinger JA, et al. Lung CD4−CD8− double-negative T cells are prominent producers of IL-17A and IFN-gamma during primary respiratory murine infection with Francisella tularensis Live Vaccine Strain. J Immunol. 2010;184(10):5791–5801.
  • Meierovics A, Yankelevich W-JC, Cowley SC. MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection. Proc Natl Acad Sci U S A. 2013;110(33):E3119–E3128.
  • Elkins KL, Cowley SC, Conlan JW. Measurement of macrophage-mediated killing of intracellular bacteria, including Francisella and Mycobacteria. Curr Protoc Immunol. 2011;93:14.25.11–14.25.13.
  • De Pascalis R, Chou AY, Bosio CM, et al. Development of functional and molecular correlates of vaccine-induced protection for a model intracellular pathogen, F. tularensis LVS. PLoS Pathog. 2012;8(1):e1002494.
  • De Pascalis R, Chou AY, Ryden P, et al. Models derived from in vitro analyses of spleen, liver, and lung leukocyte functions predict vaccine efficacy against the Francisella tularensis Live Vaccine Strain (LVS). MBio. 2014;5(2):e00936-13.
  • Yee D, Rhinehart-Jones TR, Elkins KL. Loss of either CD4+ or CD8+ T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS. J Immunol. 1996;157:5042–5048.
  • Poquet Y, Kroca M, Halary F, et al. Expansion of Vgamma9 Vdelta2 T cells is triggered by Francisella tularensis-derived phosphoantigens in tularemia but not after tularemia vaccination. Infect Immun. 1998;66(5):2107–2114.
  • Kurtz SL, Foreman O, Bosio CM, et al. Interleukin-6 is essential for primary resistance to Francisella tularensis Live Vaccine Strain infection. Infect Immun. 2013;81(2):585–597.
  • Melillo AA, Foreman O, Elkins KL. IL-12Rβ2 is critical for survival of primary Francisella tularensis LVS infection. J Leukoc Biol. 2013;93(5):657–667.
  • Melillo AA, Foreman O, Bosio CM, et al. T-bet regulates immunity to Francisella tularensis Live Vaccine Strain infection, particularly in lungs. Infect Immun. 2014;82(4):1477–1490.
  • Snoy PJ. Establishing efficacy of human products using animals: the US Food and Drug Administration’s “animal rule”. Vet Pathol. 2010;47(5):774–778.
  • Ryden P, Twine S, Shen H, et al. Correlates of protection following vaccination of mice with gene deletion mutants of Francisella tularensis subspecies tularensis strain, SCHU S4 that elicit varying degrees of immunity to systemic and respiratory challenge with wild-type bacteria. Mol Immunol. 2013;54(1):58–67.
  • Twine S, Shen H, Harris G, et al. BALB/c mice, but not C57BL/6 mice immunized with a ΔclpB mutant of Francisella tularensis subspecies tularensis are protected against respiratory challenge with wild-type bacteria: association of protection with post-vaccination and post-challenge immune responses. Vaccine. 2012;30(24):3634–3645.
  • Shen H, Harris G, Chen W, et al. Molecular immune responses to aerosol challenge with Francisella tularensis in mice inoculated with live vaccine candidates of varying efficacy. PLoS One. 2010;5(10):e13349.
  • De Pascalis R, Mittereder L, Kennett NJ, et al. Activities of murine peripheral blood lymphocytes provide immune correlates that predict Francisella tularensis vaccine efficacy. Infect Immun. 2016;84:1054–1061.
  • Waag DM, Sändstrom G, England MJ, et al. Immunogenicity of a new lot of Francisella tularensis live vaccine strain in human volunteers. FEMS Immunol Med Microbiol. 1996;13(3):205–209.
  • Waag DM, Mckee KT Jr, Sandstrom G, et al. Cell-mediated and humoral immune responses after vaccination of human volunteers with the live vaccine strain of Francisella tularensis. Clin Diagn Lab Immunol. 1995;2(2):143–148.
  • Paranavitana C, Pittman PR, Velauthapillai M, et al. Transcriptional profiling of Francisella tularensis infected peripheral blood mononuclear cells: a predictive tool for tularemia. FEMS Immunol Med Microbiol. 2008;54(1):92–103.
  • Paranavitana C, Zelazowska E, Dasilva L, et al. Th17 cytokines in recall responses against Francisella tularensis in humans. J Interferon Cytokine Res. 2010;30(7):471–476.
  • Bosio CM, Elkins KL. Susceptibility to secondary Francisella tularensis Live Vaccine Strain infection in B-cell-deficient mice is associated with neutrophilia but not with defects in specific T-cell-mediated immunity. Infect Immun. 2001;69:194–203.
  • Elkins KL, Cooper A, Colombini SM, et al. In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of Interleukin-12 (IL-12) but not on IL-12 p70. Infect Immun. 2002;70:1936–1948.
  • Sandström G, Löfgren S, Tärnvik A. A capsule-deficient mutant of Francisella tularensis LVS exhibits enhanced sensitivity to killing by serum but diminished sensitivity to killing by polymorphonuclear leukocytes. Infect Immun. 1988;56:1194–1202.
  • Kurtz SL, Elkins KL. Correlates of vaccine-induced protection against Mycobacterium tuberculosis revealed in comparative analyses of lymphocyte populations. Clin Vaccine Immunol. 2015;22:1096–1108.
  • Elkins KL, Colombini SM, Meierovics AI, et al. Survival of secondary lethal systemic Francisella LVS challenge depends largely on interferon gamma. Microbes Infect. 2010;12(1):28–36.
  • Hewetson JF, Little SF, Ivins BE, et al. An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals. Vaccine. 2008;26(33):4262–4266.
  • Fay MP, Follmann DA, Lynn F, et al. Anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge. Sci Transl Med. 2012;4(151):151ra126.
  • Chen L, Schiffer JM, Dalton S, et al. Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques. Clin Vaccine Immunol. 2014;21(11):1512–1520.
  • Williamson ED, Oyston PC. Protecting against plague: towards a next-generation vaccine. Clin Exp Immunol. 2013;172(1):1–8.
  • Silva EB, Goodyear A, Sutherland MD, et al. Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine. Infect Immun. 2013;81(12):4626–4634.
  • Hoft DF, Worku S, Kampmann B, et al. Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. J Infect Dis. 2002;186(10):1448–1457.
  • Ohtake S, Martin RA, Saxena A, et al. Formulation and stabilization of Francisella tularensis Live Vaccine Strain. J Pharm Sci. 2011;100(8):3076–3087.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.