A two-codon mutant of cholera toxin lacking ADP-ribosylating activity functions as an effective adjuvant for eliciting mucosal and systemic cellular immune responses to peptide antigens.
Vaccination with peptide antigens is an effective strategy against mucosal viral infections. We tested a two-codon mutant of cholera toxin (CT-2*) lacking ADP-ribosylating activity and toxicity as a mucosal adjuvant for T cell epitope peptides for intranasal immunization of mice. Efficient induction of helper and cytotoxic T lymphocyte responses associated with TH1 cytokine production were observed in the systemic and mucosal compartments including nasal, gut, and vaginal associated lymphoid tissues. Single or multiple dosing with the peptide antigen and CT-2* induced strong memory immunity without tolerance. These results demonstrate CT-2* as a suitable mucosal adjuvant for priming antigen-specific cellular immune responses.
Lomada
Dakshayani
D
Department of Veterinary Sciences, M.D. Anderson Cancer Center, The University of Texas, Bastrop, TX 78602, USA.
Gambhira
Ratish
R
Nehete
Pramod N
PN
Guhad
Faisal A
FA
Chopra
Ashok K
AK
Peterson
Johnny W
JW
Sastry
K Jagannadha
KJ
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000235:genetics*; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D003062:Codon / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D003062:Codon; D016207:Cytokines; D010455:Peptides; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin