title: Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yang
authors.affiliation: Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Oral Pathology, College of Dentistry, Howard University, Washington, DC USA.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Pang
authors.affiliation: 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.
authors.forename: Richard B S
authors.initials: RB
authors.lastname: Roden
authors.affiliation: 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.
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
keywords: Capsid; DNA vaccine; Human papillomavirus (HPV)