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Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence

Fahad N Almajhdi1, Tilo Senger2, Haitham M Amer3

  • 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Plos One
|November 26, 2014
PubMed

Insights

A novel DNA vaccine targeting Human Papillomavirus type 16 (HPV 16) E6 and E7 oncoproteins shows promise. One candidate effectively controlled HPV 16-positive tumors in mice, indicating potential for treating HPV-related cancers.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Persistent infection with high-risk Human Papillomavirus type 16 (HPV 16) is a primary cause of cervical, anogenital, and head and neck cancers.
  • Current therapeutic vaccine development for HPV has not advanced to late-stage clinical trials.
  • HPV oncoproteins E6 and E7 are consistently expressed in infected cells, making them ideal targets for immune-based therapies.

Purpose of the Study:

  • To develop and evaluate novel DNA vaccine candidates targeting HPV-16 E6 and E7 oncoproteins.
  • To assess the immunogenicity and therapeutic efficacy of differently rearranged HPV-16 E6/E7 DNA sequences.

Main Methods:

  • Eight DNA vaccine candidates were constructed with rearranged HPV-16 E6 and E7 sequences, fused to a J-domain and SV40 enhancer.
  • Vaccine candidates were tested in mice to assess E6- and E7-specific cellular immune responses.
  • Efficacy was evaluated by observing the control of HPV 16-positive syngeneic tumor growth in regression experiments.

Main Results:

  • One of the eight DNA vaccine candidates induced potent E6- and E7-specific cellular immune responses in mice.
  • This lead vaccine candidate demonstrated significant control over the growth of HPV 16-positive tumors.
  • The study suggests that sequence rearrangements within the DNA vaccine influence its immunogenicity through an undetermined mechanism.

Conclusions:

  • A novel DNA vaccine candidate shows significant potential for controlling persistent HPV 16 infections and associated malignancies.
  • The findings highlight the therapeutic potential of targeting HPV oncoproteins with DNA-based vaccines.
  • Further research is warranted to understand how sequence rearrangements impact vaccine immunogenicity.

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