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.
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.
Manuri
Pallavi R
PR
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Nehete
Bharti
B
Nehete
Pramod N
PN
Reisenauer
Rose
R
Wardell
Seth
S
Courtney
Amy N
AN
Gambhira
Ratish
R
Lomada
Dakshyani
D
Chopra
Ashok K
AK
Sastry
K Jagannadha
KJ
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*
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