Assembly of synthetic peptide vaccines by chemoselective ligation of epitopes: influence of different chemical linkages and epitope orientations on biological activity.
In this paper, we describe the assembly of synthetic peptide vaccines composed of a T helper cell epitope and a B cell epitope that were synthesized separately and then attached using three different chemoselective ligation methods: oxime bond formation, thioether bond formation and disulfide bond formation. The resulting vaccines were tested in animals to investigate their efficacy. We found that thioether bond formation gave the highest yield of material and that the chemistry involved did not adversely affect immunogenicity and biological activity of the peptide vaccine. Ligation of epitopes by oxime bond formation did not diminish biological activity either, but the yields of peptide vaccine were lower than when thioether bond formation was used. The vaccines in which a disulfide bond was used to attach the two epitopes resulted in the lowest yield and produced vaccines that also generated a weaker immune response with sub-optimal biological activity. Connecting the T helper epitope via its N-terminus or its C-terminus to the N-terminus of the B cell epitope had little influence on resulting immunogenicity and biological activity.
Zeng
W
W
Co-operative Research Centre for Vaccine Technology, Department of Microbiology and Immunology, The University of Melbourne, Parkville 3010, Victoria, Australia.
Ghosh
S
S
Macris
M
M
Pagnon
J
J
Jackson
D C
DC
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D005260:Female; D005298:Fertility / Q000276:immunology; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007987:Gonadotropin-Releasing Hormone