Live tularemia vaccine but not proteins purified from <i>Francisella tularensis</i> can confer protection against lethal <i>Listeria</i> infection in mice

Belyi, Yura F.; Petrosov, Vladimir V.; Tartakovskiĭ, I S; Suchkov, Yuri G.

doi:10.1111/j.1699-0463.1995.tb01085.x

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Unexpectedly, the L. monocytogenes vector (rLmΔactA) itself provided a small degree of cross-protection against F. tularensis . Consistent with this, the F. tularensis LVS vaccine similarly provides some protection against a lethal Listeria challenge [53–55]. Cross-protection may reflect immunoprotective responses to shared antigens of the two intracellular bacterial pathogens.…”

Section: Discussionmentioning

confidence: 75%

Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis

Jia

Lee

Clemens

et al. 2009

Vaccine

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Fransicella tularensis, the causative agent of tularemia, is in the top category (Category A) of potential agents of bioterrorism. To develop a safer vaccine against aerosolized F. tularensis, we have employed an attenuated Listeria monocytogenes, which shares with F. tularensis an intracellular and extraphagosomal lifestyle, as a delivery vehicle for F. tularensis antigens. We constructed recombinant L. monocytogenes (rLm) vaccines stably expressing 7 F. tularensis proteins including IglC (rLm/iglC), and tested their immunogenicity and protective efficacy against lethal F. tularensis challenge in mice. Mice immunized intradermally with rLm/iglC developed significant cellular immune responses to F. tularensis IglC as evidenced by lymphocyte proliferation and CD4 + and CD8+ T-cell intracellular expression of interferon gamma. Moreover, mice immunized with rLm/iglC were protected against lethal challenge with F. tularensis LVS administered by the intranasal route, a route chosen to mimic airborne infection, and, most importantly, against aerosol challenge with the highly virulent Type A F. tularensis SchuS4 strain.

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Section: Discussionmentioning

confidence: 75%

Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis

Jia

Lee

Clemens

et al. 2009

Vaccine

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“…Immunization with a killed vaccine caused local reactions, induced poor CMI responses, and failed to provide protection against respiratory F. tularensis SchuS4 challenge ( Burke, 1977 ; Baron et al, 2007 ). The live-attenuated strains including the LVS has succeeded in providing protection against a low dose of F. tularensis Schus4 challenge in mice and non-human primates, but they do not offer a high degree of protection against high dose aerosol challenge with F. tularensis SchuS4 ( Belyi et al, 1995 ; Oyston and Quarry, 2005 ; Bakshi et al, 2008 ; Barry et al, 2009 ; Mahawar et al, 2013 ; Marohn and Barry, 2013 ; Chu et al, 2014 ). Moreover, reversion to fully virulent form is always a possibility with live-attenuated vaccines.…”

Section: Introductionmentioning

confidence: 99%

An Improved Tobacco Mosaic Virus (TMV)-Conjugated Multiantigen Subunit Vaccine Against Respiratory Tularemia

et al. 2018

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Francisella tularensis, the causative agent of the fatal human disease known as tularemia is classified as a Category A Select Agent by the Centers for Disease Control. No licensed vaccine is currently available for prevention of tularemia in the United States. Previously, we published that a tri-antigen tobacco mosaic virus (TMV) vaccine confers 50% protection in immunized mice against respiratory tularemia caused by F. tularensis. In this study, we refined the TMV-vaccine formulation to improve the level of protection in immunized C57BL/6 mice against respiratory tularemia. We developed a tetra-antigen vaccine by conjugating OmpA, DnaK, Tul4, and SucB proteins of Francisella to TMV. CpG was also included in the vaccine formulation as an adjuvant. Primary intranasal (i.n.) immunization followed by two booster immunizations with the tetra-antigen TMV vaccine protected 100% mice against i.n. 10LD100 challenges dose of F. tularensis live vaccine strain (LVS). Mice receiving three immunization doses of tetra-antigen TMV vaccine showed only transient body weight loss, cleared the infection rapidly, and showed minimal histopathological lesions in lungs, liver, and spleen following a lethal respiratory challenge with F. tularensis LVS. Mice immunized with the tetra-antigen TMV vaccine also induced strong ex vivo recall responses and were protected against a lethal challenge as late as 163 days post-primary immunization. Three immunization with the tetra-antigen TMV vaccine also induced a stronger humoral immune response predominated by IgG1, IgG2b, and IgG2c antibodies than mice receiving only a single or two immunizations. Remarkably, a single dose protected 40% of mice, while two doses protected 80% of mice from lethal pathogen challenge. Immunization of Interferon-gamma (IFN-γ)-deficient mice with the tetra-antigen TMV vaccine demonstrated an absolute requirement of IFN-γ for the generation of protective immune response against a lethal respiratory challenge with F. tularensis LVS. Collectively, this study further demonstrates the feasibility of TMV as an efficient platform for the delivery of multiple F. tularensis antigens and that tetra-antigen TMV vaccine formulation provides complete protection, and induces long-lasting protective and memory immune responses against respiratory tularemia caused by F. tularensis LVS.

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“…Nonspecific symptoms of tularemia and the engineered antibiotic resistant strains undermine therapeutic options. In the last hundred years since the discovery of Ft , three broad approaches including inactivated, live attenuated, or subunit vaccines have been employed for tularemia vaccine development, but none of them have been successful [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Although, a Live Vaccine Strain (LVS) developed from the Russian strain Ft subspecies holarctica S15 is protective, it retains residual virulence in humans when immunized via aerosol or intranasal (i.n.)…”

Section: Introductionmentioning

confidence: 99%

Preclinical Testing of a Vaccine Candidate against Tularemia

Suresh

Sunagar

et al. 2015

PLoS ONE

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Tularemia is caused by a gram-negative, intracellular bacterial pathogen, Francisella tularensis (Ft). The history weaponization of Ft in the past has elevated concerns that it could be used as a bioweapon or an agent of bioterrorism. Since the discovery of Ft, three broad approaches adopted for tularemia vaccine development have included inactivated, live attenuated, or subunit vaccines. Shortcomings in each of these approaches have hampered the development of a suitable vaccine for prevention of tularemia. Recently, we reported an oxidant sensitive mutant of Ft LVS in putative EmrA1 (FTL_0687) secretion protein. The emrA1 mutant is highly sensitive to oxidants, attenuated for intramacrophage growth and virulence in mice. We reported that EmrA1 contributes to oxidant resistance by affecting the secretion of antioxidant enzymes SodB and KatG. This study investigated the vaccine potential of the emrA1 mutant in prevention of respiratory tularemia caused by Ft LVS and the virulent SchuS4 strain in C57BL/6 mice. We report that emrA1 mutant is safe and can be used at an intranasal (i. n.) immunization dose as high as 1x106 CFU without causing any adverse effects in immunized mice. The emrA1 mutant is cleared by vaccinated mice by day 14–21 post-immunization, induces minimal histopathological lesions in lungs, liver and spleen and a strong humoral immune response. The emrA1 mutant vaccinated mice are protected against 1000–10,000LD100 doses of i.n. Ft LVS challenge. Such a high degree of protection has not been reported earlier against respiratory challenge with Ft LVS using a single immunization dose with an attenuated mutant generated on Ft LVS background. The emrA1 mutant also provides partial protection against i.n. challenge with virulent Ft SchuS4 strain in vaccinated C57BL/6 mice. Collectively, our results further support the notion that antioxidants of Ft may serve as potential targets for development of effective vaccines for prevention of tularemia.

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Live tularemia vaccine but not proteins purified from Francisella tularensis can confer protection against lethal Listeria infection in mice

Cited by 6 publications

References 19 publications

Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis

Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis

An Improved Tobacco Mosaic Virus (TMV)-Conjugated Multiantigen Subunit Vaccine Against Respiratory Tularemia

Preclinical Testing of a Vaccine Candidate against Tularemia

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