We have devised and are continuing to improve two different recombinant antigen delivery systems to analyze the immunological host responses to antigens specified by cloned genes. The first employs recombinant avirulent delta cya delta crp Salmonella strains, exhibiting stable high- level expression of cloned gene products in vivo due to use of a balanced-lethal host-vector system. The recombinant avirulent Salmonella strains target antigens to lymphoid tissues to induce secretory, humoral and cellular immune responses. The second employs oral immunization with plant meal prepared from transgenic plants expressing antigens specified by cloned genes to induce oral tolerance to overcome autoimmunity and local and possibly generalized secretory immune responses. The expressed antigens will include colonization and virulence antigens of pathogens, other bacterial antigens and allergens. Our objectives will be to (1) further improve and develop Salmonella antigen delivery systems to improve stability, immunogenicity, host specificity and containment, (2) use recombinant avirulent Salmonella expressing Streptococcus mutans colonization antigens to define the different and/or overlapping epitopes responsible for secretory, humoral and cellular immune responses, (3) use recombinant avirulent Salmonella expressing various antigens with and without fusion to an oral adjuvant to determine the influence of antigen amount, form and location in Salmonella on the type, level and duration of immune responses, (4) further improve and develop means for generating transgenic plants stably expressing high levels of foreign antigens specified by cloned genes, and (5) use transgenic plant materials containing foreign antigens for oral immunization of laboratory animals to investigate induction of local and generalized mucosal immune responses and the potential and means to induce tolerance. We will employ modern technologies in the fields of microbiology, immunology, genetics, molecular biology, microscopy, plant biotechnology and animal science in our research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006669-09
Application #
3220177
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1983-04-01
Project End
1997-02-28
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Curtiss 3rd, Roy; Wanda, Soo-Young; Gunn, Bronwyn M et al. (2009) Salmonella enterica serovar typhimurium strains with regulated delayed attenuation in vivo. Infect Immun 77:1071-82
Bollen, Wendy S; Gunn, Bronwyn M; Mo, Hua et al. (2008) Presence of wild-type and attenuated Salmonella enterica strains in brain tissues following inoculation of mice by different routes. Infect Immun 76:3268-72
Kong, Wei; Wanda, Soo-Young; Zhang, Xin et al. (2008) Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment. Proc Natl Acad Sci U S A 105:9361-6
Konjufca, Vjollca; Jenkins, Mark; Wang, Shifeng et al. (2008) Immunogenicity of recombinant attenuated Salmonella enterica serovar Typhimurium vaccine strains carrying a gene that encodes Eimeria tenella antigen SO7. Infect Immun 76:5745-53
Konjufca, Vjollca; Wanda, Soo-Young; Jenkins, Mark C et al. (2006) A recombinant attenuated Salmonella enterica serovar Typhimurium vaccine encoding Eimeria acervulina antigen offers protection against E. acervulina challenge. Infect Immun 74:6785-96
Uzzau, Sergio; Marogna, Gavino; Leori, Guido Sisinnio et al. (2005) Virulence attenuation and live vaccine potential of aroA, crp cdt cya, and plasmid-cured mutants of Salmonella enterica serovar Abortusovis in mice and sheep. Infect Immun 73:4302-8
Kang, Ho Young; Curtiss 3rd, Roy (2003) Immune responses dependent on antigen location in recombinant attenuated Salmonella typhimurium vaccines following oral immunization. FEMS Immunol Med Microbiol 37:99-104
Kang, Ho Young; Dozois, Charles M; Tinge, Steven A et al. (2002) Transduction-mediated transfer of unmarked deletion and point mutations through use of counterselectable suicide vectors. J Bacteriol 184:307-12
Kang, Ho Young; Srinivasan, Jay; Curtiss 3rd, Roy (2002) Immune responses to recombinant pneumococcal PspA antigen delivered by live attenuated Salmonella enterica serovar typhimurium vaccine. Infect Immun 70:1739-49
Frey, S E; Bollen, W; Sizemore, D et al. (2001) Bacteremia associated with live attenuated chi8110 Salmonella enterica serovar Typhi ISP1820 in healthy adult volunteers. Clin Immunol 101:32-7

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