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

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 v...

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Autores principales: Yang, Benjamin, Yang, Andrew, Peng, Shiwen, Pang, Xiaowu, Roden, Richard B.S., Wu, T.-C., Hung, Chien-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480891/
https://www.ncbi.nlm.nih.gov/pubmed/26113972
http://dx.doi.org/10.1186/s13578-015-0025-y
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author Yang, Benjamin
Yang, Andrew
Peng, Shiwen
Pang, Xiaowu
Roden, Richard B.S.
Wu, T.-C.
Hung, Chien-Fu
author_facet Yang, Benjamin
Yang, Andrew
Peng, Shiwen
Pang, Xiaowu
Roden, Richard B.S.
Wu, T.-C.
Hung, Chien-Fu
author_sort Yang, Benjamin
collection PubMed
description 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.
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spelling pubmed-44808912015-06-26 Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination Yang, Benjamin Yang, Andrew Peng, Shiwen Pang, Xiaowu Roden, Richard B.S. Wu, T.-C. Hung, Chien-Fu Cell Biosci Research 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. BioMed Central 2015-06-25 /pmc/articles/PMC4480891/ /pubmed/26113972 http://dx.doi.org/10.1186/s13578-015-0025-y Text en © Yang et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yang, Benjamin
Yang, Andrew
Peng, Shiwen
Pang, Xiaowu
Roden, Richard B.S.
Wu, T.-C.
Hung, Chien-Fu
Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title_full Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title_fullStr Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title_full_unstemmed Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title_short Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination
title_sort co-administration with dna encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic hpv dna vaccination
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480891/
https://www.ncbi.nlm.nih.gov/pubmed/26113972
http://dx.doi.org/10.1186/s13578-015-0025-y
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