title: T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.
abstract: Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Levy
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Flashner
authors.forename: Avital
authors.initials: A
authors.lastname: Tidhar
authors.forename: Ayelet
authors.initials: A
authors.lastname: Zauberman
authors.forename: Moshe
authors.initials: M
authors.lastname: Aftalion
authors.forename: Shirley
authors.initials: S
authors.lastname: Lazar
authors.forename: David
authors.initials: D
authors.lastname: Gur
authors.forename: Avigdor
authors.initials: A
authors.lastname: Shafferman
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Mamroud
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization / Q000379:methods; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010930:Plague / Q000276:immunology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; C086725:caf1 protein, Yersinia pestis; D003165:Complement System Proteins