Live Attenuated Vaccine Protects against Pulmonary Challenge in Rats and Non-human Primates


Francisella tularensis is a bacterium that causes the infectious disease tularemia. F. tularensis has been developed as a biothreat agent, because it causes high morbidity and mortality when spread by aerosol. There is currently no approved vaccine for human use, making mankind vulnerable to the illicit use of this organism. F. tularensis contains a cluster of genes in the Francisella Pathogenicity Island (FPI) that are required for replication inside host macrophages and virulence. In the current study we created a live vaccine strain by inactivating an FPI gene, iglD, in a closely-related species that does not cause disease in humans, F. novicida (Fn iglD). We demonstrate that vaccination with Fn iglD protects against exposure to airborne F. tularensis. Fn iglD vaccination induces antibody and cellular immune responses and protects two different animals, rats and non-human primates, against lethal pulmonary tularemia challenges. These two animal models reflect human sensitivity to F. tularensis. Our results suggest that a vaccine made from the low virulence F. novicida will protect humans against aerosol exposure to this dangerous pathogen.


Vyšlo v časopise: Live Attenuated Vaccine Protects against Pulmonary Challenge in Rats and Non-human Primates. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004439
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004439

Souhrn

Francisella tularensis is a bacterium that causes the infectious disease tularemia. F. tularensis has been developed as a biothreat agent, because it causes high morbidity and mortality when spread by aerosol. There is currently no approved vaccine for human use, making mankind vulnerable to the illicit use of this organism. F. tularensis contains a cluster of genes in the Francisella Pathogenicity Island (FPI) that are required for replication inside host macrophages and virulence. In the current study we created a live vaccine strain by inactivating an FPI gene, iglD, in a closely-related species that does not cause disease in humans, F. novicida (Fn iglD). We demonstrate that vaccination with Fn iglD protects against exposure to airborne F. tularensis. Fn iglD vaccination induces antibody and cellular immune responses and protects two different animals, rats and non-human primates, against lethal pulmonary tularemia challenges. These two animal models reflect human sensitivity to F. tularensis. Our results suggest that a vaccine made from the low virulence F. novicida will protect humans against aerosol exposure to this dangerous pathogen.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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