Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

Benjamin Yang, Andrew Yang, Shiwen Peng, Xiaowu Pang, Richard S Roden, Tzyy Choou Wu, Chien-Fu Hung

Research output: Contribution to journalArticle

Abstract

Background: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8+ T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4+ T cell help for the enhancement of antigen-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. Result: We showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8+ in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4+ T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8+ T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16L1/L2 system. Conclusion: Our strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer.

Original languageEnglish (US)
Article number35
JournalCell and Bioscience
Volume5
Issue number1
DOIs
StatePublished - Jun 25 2015

Keywords

  • Capsid
  • DNA vaccine
  • Human papillomavirus (HPV)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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