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).
Moyle
Peter M
PM
School of Pharmacy, The University of Queensland, St. Lucia 4072, Queensland, Australia.
Olive
Colleen
C
Ho
Mei-Fong
MF
Pandey
Manisha
M
Dyer
Joanne
J
Suhrbier
Andreas
A
Fujita
Yoshio
Y
Toth
Istvan
I
D000818:Animals; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005947:Glucose / Q000737:chemistry; D052162:Human papillomavirus 16 / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008074:Lipoproteins / Q000138:chemical synthesis* / Q000276:immunology / Q000627:therapeutic use; D008358:Mannose / Q000737:chemistry; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000737:chemistry; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000138:chemical synthesis* / Q000276:immunology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000276:immunology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000378:metabolism; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D000939:Epitopes; D037181:Lectins, C-Type; D008074:Lipoproteins; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D010455:Peptides; D011956:Receptors, Cell Surface; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D005947:Glucose; D008358:Mannose