Antigenic features of protein carriers commonly used in immunisation trials

Biotechnology Letters - Tập 32 - Trang 1215-1221 - 2010
Pieranna Chiarella1, Bärbel Edelmann2, Vito M. Fazio1, Alan M. Sawyer3, Ario de Marco4
1Laboratory of Molecular Medicine and Biotechnology, CIR, University of Rome Campus Bio-medico, Rome, Italy
2Institut für Immunologie, Universität Kiel, Kiel, Germany
3Monoclonal Antibody Core Facility, Mouse Biology Programme-EMBL, Monterotondo Scalo, Italy
4Cogentech, IFOM-IEO Campus, Milan, Italy

Tóm tắt

An aluminium hydroxide adjuvant induced a more elevated and rapid immune responses against short peptides conjugated to the Keyhole Lympet Hemocyanin carrier than immuneasy adjuvant. Furthermore, since carrier proteins may compete with the fused or chemically linked polypeptides in eliciting antigen-specific immune response, we classified the immunogenicity of the most common carrier proteins used in molecular biology for antigen expression and mouse immunisation. The disulfide isomerase protein A gave a carrier with the lowest immunogenicity whilst disulfide isomerase protein C gave the highest immunogenicity and therefore should be avoided as a fusion partner. Using this protein as a model, we identified and located the immunodominant epitopes along its sequence. These results now enable the combination of carrier and immunisation conditions to be optimized.

Tài liệu tham khảo

Bossi S, Ferranti B, Martinelli C, Capasso P, de Marco A (2010) Antibody-mediated purification of co-expressed antigen-antibody complexes. Protein Express Purif. doi:10.1016/j.pep.2010.01.003 Chiarella P, Massi E, De Robertis M, Signori E, Fazio VM (2007) Adjuvant in vaccines and for immunisation: current trends. Expert Opin Biol Ther 7:1551–1562 De Marco V, Stier G, Blandin S, de Marco A (2004) Comparison of NusA and GST as fusion partners for recombinant expression in E. coli. Biochem Biophys Res Commun 322:766–771 De Masi F, Chiarella P, Wilhelm H, Massimi M, Bullard B, Ansorge W, Sawyer A (2005) High-throughput mouse monoclonal antibodies using antigen microarrays. Proteomics 5:4070–4081 Di John D, Torres JR, Murillo J, Herrington DA et al (1989) Effect of priming with carrier on response to conjugate vaccine. Lancet 2:1415–1418 Dümmler A, Lawrence AM, de Marco A (2005) Simplified screening for the detection of soluble fusion constructs expressed in E. coli using a modular set of vectors. Microb Cell Fact 4:34 Herzenberg LA, Tokuhisa T, Herzenberg LA (1980) Carrier-priming leads to hapten-specific suppression. Nature 285:664–667 Kirkley JE, Goldstein AL, Naylor PH (2001) Effect of peptide-carrier coupling on peptide-specific immune response. Immunobiology 203:601–615 Krieg AM (1990) Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochim Biophys Acta 1489:107–116 Mutwiri G, Gerdts V, Lopez M, Babiul LA (2007) Innate immunity and new adjuvants. Rev Sci Tech 26:147–156 Sad S, Gupta HM, Talwar GP, Raghupathy R (1991) Carrier induced suppression of the antibody response to a “self” hapten. Immunology 74:223–227 Schutze MP, Deriaud E, Przewlocki G, LeClerc C (1989) Carrier-induced epitopic suppression is initiated through clonal dominance. J Immunol 142:2635–2640 Tang HY, Speicher DW (2004) Identification of alternative products and optimization of NTCB cyanylation and cleavage at cysteine residues. Anal Biochem 334:48–61 Wilson-Welder JH, Torres MP, Kipper MJ, Mallapragada SK, Wannemuehler MJ, Narasimhan B (2009) Vaccine adjuvants: current challenge and future approaches. J Pharm Sci 98:1278–1316