title: Hp91 immunoadjuvant: An HMGB1-derived peptide for development of therapeutic HPV vaccines.
abstract: BACKGROUND
  High percentage of human cervical malignancy is related to human papillomavirus (HPV) infections. Thus, it is important to find novel non-invasive treatment strategies among various therapeutic HPV vaccines. In current study, we investigated the protective and therapeutic effects of DNA- and protein-based vaccines using HPV16 E7 as a model antigen in tumor mice model. In this line, the full length of high-mobility group box 1 (HMGB1) protein as well as an HMGB1-derived short peptide (Hp91) was used as an adjuvant for stimulating adaptive immunity and developing the potency of these vaccines.
  
  
  METHODS
  DNA vaccination of HPV16 E7 with HMGB1 was performed as the complexed and conjugated forms. The immunostimulatory properties of Hp91 peptide along with Hp121 control peptide were compared to Montanide 720 in protein vaccination.
  
  
  RESULTS
  Our data showed that co-immunization of HPV16 E7 protein with Hp91 peptide or Hp91+Hp121 peptides significantly increased the secretion of IFN-γ, IgG2a antibody response, and protected 100% of mice against a TC-1 tumor challenge. Furthermore, the linkage of HMGB1 with E7 antigen led to enhance the immunogenicity of DNA vaccine especially in combination with Hp91 and Hp121 peptides.
  
  
  CONCLUSIONS
  These findings suggest that Hp91 peptide, and the full length of HMGB1 gene could be an efficient adjuvant for improvement of therapeutic HPV protein- and DNA-based vaccines, respectively.
authors.affiliation: Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Talebi
authors.affiliation: Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran. Electronic address: azam.bolhassani@yahoo.com.
authors.forename: Azam
authors.initials: A
authors.lastname: Bolhassani
authors.affiliation: Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Sadat
authors.affiliation: Department of Medical Lab Technology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran .
authors.forename: Rouhollah
authors.initials: R
authors.lastname: Vahabpour
authors.affiliation: Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Agi
authors.affiliation: Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Shahbazi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral; D045744:Cell Line, Tumor; D005260:Female; D015967:Gene Expression Regulation, Viral; D024243:HMGB1 Protein / Q000737:chemistry*; D052162:Human papillomavirus 16 / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053918:Papillomavirus Vaccines / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D024243:HMGB1 Protein; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019444:Vaccines, DNA
keywords: Adjuvant; HMGB1 nuclear protein; HPV; Hp91 peptide; Vaccine