Toward the development of prophylactic and therapeutic human papillomavirus type-16 lipopeptide vaccines.

Four lipid-core peptide systems were synthesized using stepwise solid-phase peptide synthesis, incorporating a sequence from the human papillomavirus type-16 (HPV-16) E7 protein (E744-62), for the purpose of developing vaccines against HPV-16 associated cervical cancer. d-Mannose was conjugated to the vaccine in order to investigate whether the targeting of dendritic cell mannose receptors would improve vaccine efficacy. The ability of the vaccines to clear or reduce the size of HPV-16 associated tumors was assessed in C57BL/6 (H-2b) mice using the TC-1 HPV-16 tumor model. Overall, significant reductions in the size of TC-1 tumors were observed in the mouse model, with the conjugation of mannose to these vaccines demonstrated to clear or reduce the size of TC-1 tumors to a greater extent than non-mannose-containing vaccines (37 out of 40 versus 21 out of 30 tumors cleared, respectively).

[1]  Stephen B. H. Kent,et al.  In situ neutralization in Boc-chemistry solid phase peptide synthesis. Rapid, high yield assembly of difficult sequences. , 2009 .

[2]  R. Roden,et al.  How will HPV vaccines affect cervical cancer? , 2006, Nature Reviews Cancer.

[3]  I. Toth,et al.  A lipophilic adjuvant carrier system for antigenic peptides , 2001, Letters in Peptide Science.

[4]  C. Specht,et al.  A Model Vaccine Exploiting Fungal Mannosylation to Increase Antigen Immunogenicity1 , 2005, The Journal of Immunology.

[5]  T. Keler,et al.  Mannose receptor-targeted vaccines , 2004, Expert opinion on biological therapy.

[6]  M. Weinstein,et al.  A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV‐16/18 vaccine , 2003, International journal of cancer.

[7]  T. Rohan,et al.  Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. , 2003, Journal of the National Cancer Institute.

[8]  P. Arya,et al.  Automated high-throughput synthesis of artificial glycopeptides. Small-molecule probes for chemical glycobiology. , 2002, Journal of combinatorial chemistry.

[9]  V. Hruby,et al.  Solid-phase synthesis of O-linked glycopeptide analogues of enkephalin. , 2001, The Journal of organic chemistry.

[10]  S. Gordon,et al.  Potential role of the mannose receptor in antigen transport. , 1999, Immunology letters.

[11]  H. Hanzawa,et al.  Synthesis of a tetrahydropyrano[2,3-d]oxazole analogue of trehazolin , 1996 .

[12]  F. Guarnieri,et al.  Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. , 1996, Cancer research.

[13]  T. Vojkovský,et al.  Detection of secondary amines on solid phase. , 1995, Peptide research.

[14]  I. Toth,et al.  A combined adjuvant and carrier system for enhancing synthetic peptides immunogenicity utilising lipidic amino acids , 1993 .

[15]  I. Frazer,et al.  A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  I. Toth,et al.  Lipidic peptides, I. Synthesis, resolution and structural elucidation of lipidic amino acids and their homo- and hetero-oligomers , 1990 .

[17]  J. Tam,et al.  Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. B. Merrifield,et al.  Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. , 1981, Analytical biochemistry.

[19]  L. Thornell,et al.  A Qualitative Test for Monitoring Coupling Completeness in Solid Phase Peptide Synthesis Using Chloranil. , 1979 .

[20]  H. Paulsen,et al.  SYNTHESES OF β-D-MANNOPYRANOSYL AZIDES, INVESTIGATION OF THE ANOMERIC STRUCTURES , 1978 .