Intranasal vaccination with a defined attenuated Francisella novicida strain induces gamma interferon-dependent antibody-mediated protection against tularemia.
Francisella tularensis is an intracellular gram-negative bacterium that is the causative agent of tularemia and a potential bioweapon. We have characterized the efficacy of a defined F. novicida mutant (DeltaiglC) as a live attenuated vaccine against subsequent intranasal challenge with the wild-type organism. Animals primed with the F. novicida DeltaiglC (KKF24) mutant induced robust splenic gamma interferon (IFN-gamma) and interleukin-12 (IL-12) recall responses with negligible IL-4 production as well as the production of antigen-specific serum immunoglobulin G1 (IgG1) and IgG2a antibodies. BALB/c mice vaccinated intranasally (i.n.) with KKF24 and subsequently challenged with wild-type F. novicida (100 and 1,000 50% lethal doses) were highly protected (83% and 50% survival, respectively) from the lethal challenges. The protection conferred by KKF24 vaccination was shown to be highly dependent on endogenous IFN-gamma production and also was mediated by antibodies that could be adoptively transferred to naive B-cell-deficient mice by inoculation of immune sera. Collectively, the results demonstrate that i.n. vaccination with KKF24 induces a vigorous Th1-type cytokine and antibody response that is protective against subsequent i.n. challenge with the wild-type strain. This is the first report of a defined live attenuated strain providing protection against the inhalation of F. novicida.
Pammit
Michael A
MA
Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Raulie
Erin K
EK
Lauriano
Crystal M
CM
Klose
Karl E
KE
Arulanandam
Bernard P
BP
D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D005603:Francisella / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma