title: Intranasal immunization with synthetic peptides corresponding to the E6 and E7 oncoproteins of human papillomavirus type 16 induces systemic and mucosal cellular immune responses and tumor protection.
abstract: The E6 and E7 oncoproteins of the high-risk HPV type16 represent ideal targets for HPV vaccine development, they being consistently expressed in cervical cancer lesions. Since HPV-16 is primarily transmitted through genital mucosal route, mucosal immune responses constitute an essential feature for vaccination strategies against HPV-associated lesions. We present here evidence showing that mucosal immunization of mice by the intranasal route with a mixture of peptides E7(44-62) and E6(43-57) from the E7 and E6 oncoproteins of HPV-16, respectively, using a mutant cholera toxin adjuvant (CT-2*), primed strong antigen-specific cellular immune responses in systemic and mucosal tissues. Significant levels of IFN-gamma production by both CD4 and CD8 cells were observed along with CTL responses that were effective against both peptide-pulsed targets as well as syngeneic tumor cells (TC-1) expressing the cognate E6 and E7 proteins. Furthermore, mice immunized with the peptide mixture and CT-2* effectively resisted TC-1 tumor challenge. These results together with our earlier observations that T cell responses to these peptides correlate with recurrence-free survival in women after ablative treatment for HPV-associated cervical intraepithelial neoplasia, support the potential of these E6 and E7 peptides for inclusion in vaccine formulations.
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pallavi R
authors.initials: PR
authors.lastname: Manuri
authors.forename: Bharti
authors.initials: B
authors.lastname: Nehete
authors.forename: Pramod N
authors.initials: PN
authors.lastname: Nehete
authors.forename: Rose
authors.initials: R
authors.lastname: Reisenauer
authors.forename: Seth
authors.initials: S
authors.lastname: Wardell
authors.forename: Amy N
authors.initials: AN
authors.lastname: Courtney
authors.forename: Ratish
authors.initials: R
authors.lastname: Gambhira
authors.forename: Dakshyani
authors.initials: D
authors.lastname: Lomada
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage; D005260:Female; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma; D002772:Cholera Toxin