Humoral immune responses and protective efficacy of sequential B- and T-cell epitopes of V antigen of Yersinia pestis by intranasal immunization in microparticles.
Capsular F1 and secretory V antigen are the putative vaccine candidates for plague, caused by Yersinia pestis. Contemplating this, we studied the immunogenicity and protective efficacy of collinearly synthesized B- and T-cell epitopes (B-T constructs) of V antigen entrapped in poly (DL-lactide-co-glycolide) microparticles immunized intranasally using single dose immunization schedule in outbred, H-2(b) and H-2(d) mice. High antibody levels were observed in terms of IgG, IgA and SIgA peak titers in sera and mucosal washes to different B-T constructs. The constructs ai, bi and fi especially showed high peak antibody titers ranging from 51,200 to 204,000, which were maintained till day 120 post immunization. IgG/IgA Specific activity in sera and washes correlated well with the peak antibody titers. Moreover, all the B-T constructs showed mixed IgG1 and IgG2a/2b response, variable immunoreactivity as well as memory response with V antigen. B-T constructs, viz ai, ak, bi, fi, di and ik showed comparatively high isotype levels. These constructs showed high immunoreactivity, and good recall response with V antigen. Finally, in vivo protective study in BALB/c mice demonstrated the protective efficacy of three B-T constructs (ai, bi and fi) against lethal doses of Yersinia pestis till day 20 post challenge, while construct 'id' showed partial protection.
Uppada
Jayaprakash Babu
JB
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Khan
Arif Azam
AA
Bhat
Ajaz Ahmad
AA
Deshmukh
Ranjana
R
Rao
Donthamsetty Nageswara
DN
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral; D007156:Immunologic Memory; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010931:Plague Vaccine / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry*; D015010:Yersinia pestis / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid