a mucosal subunit vaccine protects against lethal respiratory infection with francisella tularensis lvs粘膜亚单位疫苗预防致命的呼吸道感染土拉杆菌内lv.pdfVIP

A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS 1¤a 2 2¤b 1 Amit R. Ashtekar , Jannet Katz , Qingan Xu , Suzanne M. Michalek * 1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Francisella tularensis (FT) is a highly virulent pathogen for humans and other mammals. Severe morbidity and mortality is associated with respiratory FT infection and there are concerns about intentional dissemination of this organism. Therefore, FT has been designated a category A biothreat agent and there is a growing interest in the development of a protective vaccine. In the present study, we determine the protective potential of a subunit vaccine comprised of the FT heat shock protein DnaK and surface lipoprotein Tul4 against respiratory infection with the live vaccine strain (LVS) of FT in mice. First, we establish an optimal intranasal immunization regimen in C57BL/6 mice using recombinant DnaK or Tul4 together with the adjuvant GPI-0100. The individual immunization regimens induced robust salivary IgA, and vaginal and bronchoalveolar IgA and IgG antigen-specific antibodies. Serum IgG1 and IgG2c antibody responses were also induced, indicative of a mixed type 2 and type 1 response, respectively. Next, we show that immunization with DnaK and Tul4 induces mucosal and systemic antibody responses that are comparable to that seen following immunization with each antigen alone. This immunization regimen also induced IFN-c, IL-10 and IL-17A production by splenic CD4+ T c