Synthesis of Toll-Like Receptor-2 Targeting Lipopeptides as Self-Adjuvanting Vaccines
Effective Th1- and Th2-type immune responses that result in protective immunity against pathogens can be induced by self-adjuvanting lipopeptides containing the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). The potent immunogenicity of these lipopeptides is due to their ability to activate dendritic cells by targeting and signaling through Toll-like receptor-2 (TLR-2). In addition, the simplicity and flexibility in their design as well as their ease of chemical definition and characterisation makes them highly attractive vaccine candidates for humans and animals. We describe in this chapter the techniques involved in the synthesis of an immunocontraceptive lipopeptide vaccine as well as the experimental assays carried out to evaluate its efficiency.
KeywordsSelf-adjuvanting lipopeptide peptide synthesis ELISA antibody immunocontraception
- 5.Olive, C., Clair, T., Yarwood, P., and Good, M.F. (2002) Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope. Vaccine 20(21–22), 2816–2825.CrossRefPubMedGoogle Scholar
- 7.Cassataro, J., Estein, S.M., Pasquevich, K.A., et al. (2005) Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infect. Immun. 73(12), 8079–8088.CrossRefPubMedGoogle Scholar
- 9.Lougovskoi, A.A., Okoyeh, N.J., and Chauhan, V.S. (1999) Mice immunised with synthetic peptide from N-terminal conserved region of merozoite surface antigen-2 of human malaria parasite Plasmodium falciparum can control infection induced by Plasmodium yoelii yoelii 265BY strain. Vaccine 18(9–10), 920–930.CrossRefPubMedGoogle Scholar
- 14.Chianese-Bullock, K.A., Pressley, J., Garbee, C., et al. (2005) MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma. J. Immunol. 174(5), 3080–3086.PubMedGoogle Scholar