Summary
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Deliyannis, G., Jackson, D.C., Ede, N.J., et al. (2002) Induction of long-term memory CD8(+) T cells for recall of viral clearing responses against influenza virus. J. Virol. 76(9), 4212–4221.
Egan, M.A., Chong, S.Y., Hagen, M., et al. (2004) A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques. Vaccine 22(27–28), 3774–3788.
Halassy, B., Mateljak, S., Bouche, F.B., et al. (2006) Immunogenicity of peptides of measles virus origin and influence of adjuvants. Vaccine 24(2), 185–194.
Jackson, D.C., Lau, Y.F., Le, T., et al. (2004) A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc. Natl. Acad. Sci. USA 101(43), 15440–15445.
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.
Taouji, S., Nomura, I., Giguere, S., et al. (2004) Immunogenecity of synthetic peptides representing linear B-cell epitopes of VapA of Rhodococcus equi. Vaccine 22(9–10), 1114–1123.
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.
Ben-Yedidia, T., Tarrab-Hazdai, R., Schechtman, D., and Arnon, R. (1999) Intranasal administration of synthetic recombinant peptide-based vaccine protects mice from infection by Schistosoma mansoni. Infect. Immun. 67(9), 4360–4366.
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.
Audran, R., Cachat, M., Lurati, F., et al. (2005) Phase I malaria vaccine trial with a long synthetic peptide derived from the merozoite surface protein 3 antigen. Infect. Immun. 73(12), 8017–8026.
Smith, J.W., 2nd, Walker, E.B., Fox, B.A., et al. (2003) Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. J. Clin. Oncol. 21(8), 1562–1573.
Valmori, D., Dutoit, V., Ayyoub, M., et al. (2003) Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine. Cancer Immun. 3, 15.
Noguchi, M., Itoh, K., Suekane, S., et al. (2004) Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer. Cancer Sci. 95(1), 77–84.
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.
Ghosh, S. and Jackson, D.C. (1999) Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines. Int. Immunol. 11(7), 1103–1110.
Ferro, V.A., Khan, M.A., McAdam, D., et al. (2004) Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)—a histological comparison in male animals. Vet. Immunol. Immunopathol. 101(1–2), 73–86.
Zeng, W., Ghosh, S., Macris, M., Pagnon, J., and Jackson, D.C. (2001) Assembly of synthetic peptide vaccines by chemoselective ligation of epitopes: influence of different chemical linkages and epitope orientations on biological activity. Vaccine 19(28–29), 3843–3852.
Jinshu, X., Jingjing, L., Duan, P., et al. (2005) A synthetic gonadotropin-releasing hormone (GnRH) vaccine for control of fertility and hormone dependent diseases without any adjuvant. Vaccine 23(40), 4834–4843.
Mesa, C. and Fernandez, L.E. (2004) Challenges facing adjuvants for cancer immunotherapy. Immunol. Cell Biol. 82(6), 644–650.
Pashine, A., Valiante, N.M., and Ulmer, J.B. (2005) Targeting the innate immune response with improved vaccine adjuvants. Nat. Med. 11(4 Suppl), S63–68.
BenMohamed, L., Belkaid, Y., Loing, E., Brahimi, K., Gras-Masse, H., and Druilhe, P. (2002) Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant. Eur. J. Immunol. 32(8), 2274–2281.
Le Gal, F.A., Prevost-Blondel, A., Lengagne, R., et al. (2002) Lipopeptide-based melanoma cancer vaccine induced a strong MART-27–35-cytotoxic T lymphocyte response in a preclinal study. Int. J. Cancer 98(2), 221–227.
Chua, B.Y., Healy, A., Cameron, P.U., et al. (2003) Maturation of dendritic cells with lipopeptides that represent vaccine candidates for hepatitis C virus. Immunol. Cell Biol. 81(1), 67–72.
Muhlradt, P.F., Kiess, M., Meyer, H., Sussmuth, R., and Jung, G. (1997) Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration. J. Exp. Med. 185(11), 1951–1958.
Zeng, W., Ghosh, S., Lau, Y.F., Brown, L.E., and Jackson, D.C. (2002) Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J. Immunol. 169(9), 4905–4912.
Nardin, E.H., Calvo-Calle, J.M., Oliveira, G.A., et al. (1998) Plasmodium falciparum polyoximes: highly immunogenic synthetic vaccines constructed by chemoselective ligation of repeat B-cell epitopes and a universal T-cell epitope of CS protein. Vaccine 16(6), 590–600.
Obert, M., Pleuger, H., Hanagarth, H.G., et al. (1998) Protection of mice against SV40 tumours by Pam3Cys, MTP-PE and Pam3Cys conjugated with the SV40 T antigen-derived peptide, K(698)-T(708). Vaccine 16(2–3), 161–169.
Mora, A.L. and Tam, J.P. (1998) Controlled lipidation and encapsulation of peptides as a useful approach to mucosal immunizations. J. Immunol. 161(7), 3616–3623.
Shimizu, T., Ohtsuka, Y., Yanagihara, Y., Kurimura, M., Takemoto, M., and Achiwa, K. (1991) Comparison of biologic activities of synthetic lipopentapeptide analogs of bacterial lipoprotein in mice. Mol. Biother. 3(1), 46–50.
Delves, P.J., Lund, T., and Roitt, I.M. (2002) Antifertility vaccines. Trends Immunol. 23(4), 213–219.
Oonk, H.B., Turkstra, J.A., Schaaper, W.M., et al. (1998) New GnRH-like peptide construct to optimize efficient immunocastration of male pigs by immunoneutralization of GnRH. Vaccine 16(11–12), 1074–1082.
Ferro, V.A. and Stimson, W.H. (1997) Immunoneutralisation of gonadotrophin releasing hormone: a potential treatment for oestrogen-dependent breast cancer. Eur. J. Cancer 33(9), 1468–1478.
Talwar, G.P. (1999) Vaccines and passive immunological approaches for the control of fertility and hormone-dependent cancers. Immunol. Rev. 171, 173–192.
Ghosh, S., Walker, J., and Jackson, D.C. (2001) Identification of canine helper T-cell epitopes from the fusion protein of canine distemper virus. Immunology 104(1), 58–66.
Wade, J.D., Bedford, J., Sheppard, R.C., and Tregear, G.W. (1991) DBU as an N alpha-deprotecting reagent for the fluorenylmethoxycarbonyl group in continuous flow solid-phase peptide synthesis. Pept. Res. 4(3), 194–199.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Chua, B.Y., Zeng, W., Jackson, D.C. (2008). Synthesis of Toll-Like Receptor-2 Targeting Lipopeptides as Self-Adjuvanting Vaccines. In: Otvos, L. (eds) Peptide-Based Drug Design. Methods In Molecular Biology™, vol 494. Humana Press. https://doi.org/10.1007/978-1-59745-419-3_14
Download citation
DOI: https://doi.org/10.1007/978-1-59745-419-3_14
Publisher Name: Humana Press
Print ISBN: 978-1-58829-990-1
Online ISBN: 978-1-59745-419-3
eBook Packages: Springer Protocols