Human papillomavirus immunogen that provides protective tumor immunity and induces tumor Regression

Juan P. Marquez, Rebecca Rivera, Kyung Hee Kang, Murray B. Gardner, Jose V Torres

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Human papillomavirus (HPV) is associated with premalignant lesions such as high-grade cervical intraepithelial neoplasia (CIN-III) with potential progression to cervical carcinoma. There are now preventive vaccines against HPV. However, no effective therapeutic vaccine or immunological treatment exists for individuals already infected or for the 470,000 women that develop high-grade dysplasia, carcinoma in situ, and cervical cancer each year. More than half of these women die from cervical cancer. Relative non-immunogenicity of HPV infection is one of the main reasons for the difficulty in designing a comprehensive therapeutic vaccine against HPV-induced premalignant lesions and cervical carcinoma. HPV E6 and E7 proteins, the major HPV oncogenes, are highly immunogenic but fail to induce cross-reactive and protective immune responses against heterologous strains. We designed and synthesized a therapeutic peptide vaccine comprised of multivalent peptide mixtures called hypervariable epitope constructs (HECs) that represent the major epitope variants of the oncogenic E7 structural protein, and assessed their immunogenicity and in vivo efficacy in mice. Our results show that this peptide vaccine can induce strong, HPV-specific, T-helper cell and CTL responses. More significantly, we have demonstrated that the vaccine is efficacious as a therapeutic agent in a mouse HPV tumor model. Therefore, the HPV HEC vaccine approach described herein can potentially prevent progression of HPV-associated premalignant lesions, and may also be therapeutic against tumors associated with HPV.

Original languageEnglish (US)
Pages (from-to)141-152
Number of pages12
JournalViral Immunology
Volume25
Issue number2
DOIs
StatePublished - Apr 1 2012

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Immunity
Neoplasms
Papillomavirus Vaccines
Epitopes
Subunit Vaccines
Vaccines
Uterine Cervical Neoplasms
Papillomavirus E7 Proteins
Therapeutics
Carcinoma
Cervical Intraepithelial Neoplasia
Papillomavirus Infections
Carcinoma in Situ
Helper-Inducer T-Lymphocytes
Oncogenes
Peptides
Proteins

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Molecular Medicine

Cite this

Human papillomavirus immunogen that provides protective tumor immunity and induces tumor Regression. / Marquez, Juan P.; Rivera, Rebecca; Kang, Kyung Hee; Gardner, Murray B.; Torres, Jose V.

In: Viral Immunology, Vol. 25, No. 2, 01.04.2012, p. 141-152.

Research output: Contribution to journalArticle

Marquez, Juan P. ; Rivera, Rebecca ; Kang, Kyung Hee ; Gardner, Murray B. ; Torres, Jose V. / Human papillomavirus immunogen that provides protective tumor immunity and induces tumor Regression. In: Viral Immunology. 2012 ; Vol. 25, No. 2. pp. 141-152.
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