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

Benjamin Yang,Richard B.S Roden,Chien-Fu Hung,Shiwen Peng,Andrew Yang,Xiaowu Pang,T.-C Wu

doi:10.1186/s13578-015-0025-y

Benjamin Yang, Richard B.S Roden + Show 5 more

Open Access

https://doi.org/10.1186/s13578-015-0025-y

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Abstract

BackgroundDNA 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.ResultWe 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.ConclusionOur 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.

Highlights

DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)associated malignancies
BPV1 L1 or L2 DNA is observed in other papillomavirus systems, we co-administered HPV16 L1 or L2 DNA with CRT/E7 or OVA DNA vaccination
We found that mice vaccinated with CRT/E7 DNA vaccine in combination with the reverse sequence BPV1-L1 or L2 DNA did not lead to the increased frequency of E7-specific CD8+ T cell immune responses observed in mice vaccinated with CRT/E7 DNA with BPV1-L1 or L2 DNA

Summary

Introduction

DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)associated malignancies. 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. 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. Among the various therapeutic HPV vaccines currently being tested, DNA vaccines have emerged as attractive candidates for the treatment of cervical cancer and associated malignancies. It is important to consider strategies to improve DNA vaccine potency strategies (for review, see [4, 5])

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