title: Cell-mediated immune response and Th/Th cytokine profile of B-T constructs of F1 and V antigen of Yersinia pestis.
abstract: Yersinia pestis, a Gram-negative bacterium, is the etiological agent of pneumonic and bubonic plague and still active in various regions of the world. Because plague is highly infectious and can readily spread by aerosolization, it poses a bioterrorism threat. The effective induction of mucosal as well as systemic immunity is an important attribute of an improved vaccine for plague. An alternative approach described here is the use of protective epitopes derived from immunodominant antigens (F1 and V) of Yersinia pestis. As T-cell immunity is also a major contributor of protection, microencapsulated B-T constructs of F1 and V antigen were used to immunize outbred and inbred mice through intranasal route, and lympho-proliferative response and cytokine profile of both Th(1) and Th(2) arms were measured in spleen, lamina propria and Peyer's patches. Three B-T constructs of F1 antigen and seven of V antigen showed significantly high T-cell response in terms of inducing systemic as well as mucosal response when compared to constituent peptides. These ten conjugates showed Th(1) cytokine profile whereas rest of the conjugates showed mixed Th(1)/Th(2) response. Four conjugates of V antigen showed high level of IL-10 production. In present study, microencapsulated B-T constructs after intranasal immunization generated systemic as well as mucosal immune response in all three sites, which offers an alternative approach for plague vaccine.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: G
authors.initials: G
authors.lastname: Gupta
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016056:Immunodominant Epitopes; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D018074:Vaccines, Conjugate; C086725:caf1 protein, Yersinia pestis; D016753:Interleukin-10