Immunization of Mice with Irradiated Pasteurella Tularensis

Gordon, M. H.; Donaldson, David M.; Wright, George G.

doi:10.1093/infdis/114.5.435

Cited by 20 publications

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“…together with IL-12 induces protection against respiratory tularemia. Gordon et al (15) previously reported that i.p. vaccination with irradiated LVS provided little protection against subsequent F. tularensis chal- lenge.…”

Section: Efficacy Of F Tularensis Inactivationmentioning

confidence: 98%

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InactivatedFrancisella tularensisLive Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion

2007

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Francisella tularensis is a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) of F. tularensis can protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated. In the present study, we examined whether immune protection in the lung could be stimulated by intranasal administration of inactivated LVS together with interleukin-12 (IL-12) as an adjuvant. LVS was inactivated by heat, paraformaldehyde treatment, or exposure to UV, and inactivation of the preparations was confirmed by assessing bacterial growth and the survival of mice after direct inoculation. We found that mucosal vaccination with inactivated LVS provided 90 to 100% protection in mice after lethal intranasal challenge with 10 4 CFU of LVS, and this protection was dependent on inclusion of exogenous IL-12 during vaccine administration. Survival of vaccinated mice after live bacterial challenge was correlated with reduced bacterial burden, decreased pulmonary inflammation, increased serum antibody titers, and lower levels of gamma interferon (IFN-␥), tumor necrosis factor alpha, and IL-6 in the lungs, livers, and spleens. Whereas NK cells were primarily responsible for the production of IFN-␥ in unvaccinated, challenged animals, vaccinated mice had increased levels of lung IFN-␥ ؉ CD4؉ T cells after challenge. Significantly, mice genetically deficient in immunoglobulin A (IgA) expression were unable to survive lethal challenge after vaccination. These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivated F. tularensis LVS.

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Section: Efficacy Of F Tularensis Inactivationmentioning

confidence: 98%

“…with various doses of irradiated LVS or F. tularensis type A strain Schu S4 and then challenged i.p. 2 weeks later with virulent organisms (15). However, this immunization scheme provided only limited protection, and a maximum of 20% of the vaccinated animals survived challenge.…”

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confidence: 99%

InactivatedFrancisella tularensisLive Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion

2007

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“…1 8 Suspensions of other organisms killed by minimum irradiation may also contain endotoxinlike activities too labile to withstand classical extzaction procedures.…”

Section: Discussionmentioning

confidence: 99%

“…le animals by vaccines killed by other methods. 1 In these and subsequent studies it was noted that injection of the irradiated organisms into mice in somewhat greater numbers than were required for immunization frequently killed the animals within 24 hours. The toxicity appeared to resemble that associated with viable suspensions of P. tularensisg and with living rickettsial anci viral suspensions,ý' although in these cases, the toxicity disappeared when the organisms were killed.…”

Section: Abstract Suspensions Of Approximately 2 X L0mentioning

confidence: 97%

“…INTRODUCTION Pasteurella tularensis vaccines rendered nonviable by exposure to ionizing radiation provoked immunity in white mice such that significant numbers of the animals survived challenge with the fully virulent SCHU strain of P. tularensis. 1 The significant degree of immunity produced was in marked contrast to the negligible protection against virulent strains afforded th. le animals by vaccines killed by other methods.…”

Section: Abstract Suspensions Of Approximately 2 X L0mentioning

confidence: 99%

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Toxicity of Pasteurella Tularensis Killed by Ionizing Radiation

Landay¹,

Wright²,

Pulliam³

et al. 1968

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Immunization with heat‐killed Francisella tularensis LVS elicits protective antibody‐mediated immunity

et al. 2007

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Francisella tularensis (FT) has been classified by the CDC as a category A pathogen because of its high virulence and the high mortality rate associated with infection via the aerosol route. Because there is no licensed vaccine available for FT, development of prophylactic and therapeutic regimens for the prevention/treatment of infection is a high priority. In this report, heat-killed FT live vaccine strain (HKLVS) was employed as a vaccine immunogen, either alone or in combination with an adjuvant, and was found to elicit protective immunity against high-dose FT live vaccine strain (FTLVS) challenge. FT-specific antibodies produced in response to immunization with HKLVS alone were subsequently found to completely protect naive mice against high-dose FT challenge in both infection-interference and passive immunization experiments. Additional passive immunization trials employing serum collected from mice immunized with a heat-killed preparation of an O-antigen-deficient transposon mutant of FTLVS (HKLVS-OAg neg ) yielded similar results. These findings demonstrated that FT-specific antibodies alone can confer immunity against high-dose FTLVS challenge, and they reveal that antibodymediated protection is not dependent upon production of LPS-specific antibodies.

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Immunization of Mice with Irradiated Pasteurella Tularensis

Cited by 20 publications

References 2 publications

InactivatedFrancisella tularensisLive Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion

InactivatedFrancisella tularensisLive Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion

Toxicity of Pasteurella Tularensis Killed by Ionizing Radiation

Immunization with heat‐killed Francisella tularensis LVS elicits protective antibody‐mediated immunity

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