Pentabody-mediated antigen delivery induces antigen-specific mucosal immune response.
An efficient immunization system is essential for the development of mucosal vaccine. Cholera toxin (CT) and Escherichia coli heat labile toxin (LT) are among the strongest adjuvants tested in experimental animals but their use in humans has been hindered by their toxicity. On the other hand, the role of their non-toxic B-subunits, CTB or LTB, in enhancing mucosal immune response is not clear. We propose here a novel strategy for the induction of mucosal immune responses. Single domain antibodies (sdAbs) against a model antigen bovine serum albumin (BSA) were raised from the antibody repertoire of a llama immunized with BSA, pentamerized by fusing the sdAbs to CTB, generating the so-called pentabodies. These pentabodies were used to deliver the antigen by mixing the two components and administering the mixture to mice intranasally. One construct was equivalent to CT in helping induce mucosal immune response. It was also found that this ability was probably due to its high affinity to BSA, providing some insight into the controversial role of CTB in mucosal immunization: at least for BSA, the model antigen BSA employed in this study, CTB has to be tightly linked to the antigen to have adjuvant/immune-enhancing effect.
Li
Shenghua
S
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6.
Zheng
Wenju
W
Kuolee
Rhonda
R
Hirama
Tomoko
T
Henry
Matthew
M
Makvandi-Nejad
Shokouh
S
Fjällman
Ted
T
Chen
Wangxue
W
Zhang
Jianbing
J
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D002161:Camelids, New World; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D000939:Epitopes / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D055503:Protein Multimerization / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D012710:Serum Albumin, Bovine; D002772:Cholera Toxin