A novel method for enhancement of peptide vaccination utilizing T-cell epitopes from conventional vaccines

Abstract

Peptide vaccines have two fundamental weak points, namely low antigenicity and MHC-restriction. In our previous study, we proposed the design of vaccine peptide to overcome these weakpoints. The vaccine was constructed in the following order, N-terminal, Arg-Gly-Asp (RGD), T-cell epitope peptide, di-lysine linker (KK) to B-cell epitope peptide. Although the vaccine peptide can basically induce B-cell epitope peptide specific antibodies to the host without immune adjuvants via intraperitoneal, subcutaneous and intranasal administration, some peptide antigens require adjuvants for antibody induction. In this study, we propose a novel protocol to enhance the immunogenicity of the peptide utilizing the host immune response to a conventional toxoid vaccine, which are lymphocyte activities to the T-cell epitope peptide. We selected multiagretope-type T-cell epitopes from diphtheria toxoid, a conventional vaccine antigen, and a part of amyloid-beta peptide (Aβ) as a B-cell epitope. The conventional toxoid vaccine was immunized before the peptide immunization. Using this protocol, we succeeded in the enhancement of the anti-Aβ antibodies induction by intranasal immunization without any immune adjuvants in C57BL/6 and Balb/c mice. Furthermore, the vaccine peptide induced the transformation of peripheral blood lymphocytes collected from healthy volunteers carrying immunities to diphtheria toxoid. These results suggested that our peptide vaccines with the novel protocol would provide an effective method for antibody induction.