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

Pallavi R. Manuri, Bharti Nehete, Pramod N. Nehete, Rose Reisenauer, Seth Wardell, Amy N. Courtney, Ratish Gambhira, Dakshyani Lomada, Ashok K. Chopra, K. Jagannadha Sastry

Research output: Contribution to journalArticle

34 Scopus citations

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 E744-62 and E643-57 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-γ 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.

Original languageEnglish (US)
Pages (from-to)3302-3310
Number of pages9
JournalVaccine
Volume25
Issue number17
DOIs
StatePublished - Apr 30 2007

Keywords

  • HPV16 E7 and E6 peptides
  • Mucosal immunization
  • Mutant cholera toxin

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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