A palmitoyl-tailed sequential oligopeptide carrier for engineering immunogenic conjugates.
The main guideline in designing effective immunogens as vaccine candidates capable of eliciting potent and specific immune responses is to combine B/T cell epitopes and adjuvants as immunostimulators on the same carrier that links the major histocompatibility complex with T cell receptors. Aiming at contributing to the development of carriers for human usage a helicoid type sequential oligopeptide carrier, SOC(n)-II, formed by the repeating tetrapeptide unit (Aib-Lys-Aib-Gly)(n), n=2-7, elongated from the amino-terminus by the palmitoyl group, known for its adjuvanticity, is now presented. The main B cell epitope, PPGMRPP, of the Sm autoantigen against which the majority of antibodies in patients with systemic lupus erythematosus is directed, was coupled to the Lys-N(epsilon)H(2) groups of the carrier in four copies and the resulting conjugate Palm-SOC(4)-II-Sm(4) was subjected to animal immunizations without utilizing any adjuvant. The induced immune response was comparable with that produced when Ac-SOC(4)-II-Sm(4) was administered in animals following the conventional immunization protocol of complete/incomplete Freund's adjuvant. High titers of anti-Palm-SOC(4)-II-Sm(4) antibodies were generated, which recognize the priming immunogenic conjugate, as well as reconstituted Sm mimics but not the carrier alone. It is concluded that Palm-SOC(n)-II carrier is a valuable tool for engineering immunogens eliciting enhanced and specific humoral immune responses.
Kargakis
Michael
M
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece.
Zevgiti
Stella
S
Krikorian
Dimitrios
D
Sakarellos-Daitsiotis
Maria
M
Sakarellos
Constantinos
C
Panou-Pomonis
Eugenia
E
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D002463:Cell Membrane Permeability / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D019308:Palmitic Acid / Q000737:chemistry*; D011817:Rabbits
D000906:Antibodies; D018796:Immunoconjugates; D009842:Oligopeptides; D019308:Palmitic Acid