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 B S Roden; T-C Wu; Chien-Fu Hung

doi:10.1186/s13578-015-0025-y

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

Cell Biosci. 2015 Jun 25:5:35. doi: 10.1186/s13578-015-0025-y. eCollection 2015.

Authors

Benjamin Yang¹, Andrew Yang¹, Shiwen Peng¹, Xiaowu Pang², Richard B S Roden³, T-C Wu⁴, Chien-Fu Hung⁵

Affiliations

¹ Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA.
² Department of Oral Pathology, College of Dentistry, Howard University, Washington, DC USA.
³ Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA ; Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
⁴ Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA ; Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
⁵ Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA ; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA.

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-1 L1 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-16 L1/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.

Keywords: Capsid; DNA vaccine; Human papillomavirus (HPV).

Abstract

Grants and funding