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Identification of promiscuous HPV16‐derived T helper cell epitopes for therapeutic HPV vaccine design
Author(s) -
Grabowska Agnieszka K.,
Kaufmann Andreas M.,
Riemer Angelika B.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28968
Subject(s) - epitope , elispot , immunology , immunotherapy , cytotoxic t cell , virology , human leukocyte antigen , ctl* , cd8 , medicine , cellular immunity , antigen , t cell , biology , immune system , in vitro , biochemistry
Cervical carcinoma and several other human papillomavirus (HPV)‐induced malignancies are a global public health problem, thus novel treatment modalities are urgently needed. Immunotherapy is an attractive option for treatment of HPV infection and HPV‐mediated premalignant and malignant lesions. However, previous approaches—focusing on the induction of cytotoxic CD8+ T cells (CTLs)—have as yet not yielded clinical successes. Since CD4+ T cells have been shown to be crucial for the induction and maintenance of CTL responses, and more recently to be also important for direct anti‐tumor immunity, human leukocyte antigen (HLA) class II‐restricted epitopes are intensively investigated to improve the efficacy of peptide‐based HPV immunotherapy. We here present an approach to identify promiscuous HPV16‐derived CD4+ T helper epitopes, which are capable of inducing T cell immunity in a large proportion of the population. To this end, we combined HLA class II epitope prediction servers with in vitro immunological evaluation to identify HPV16 E2‐, E5‐, E6‐, and E7‐derived CD4+ T cell epitopes. Candidate selected HPV16‐derived epitopes were found to be restricted by up to nine HLA‐DR molecules. Furthermore, they were found to induce frequent and robust HPV16 peptide‐specific Th1 responses in healthy donors, as monitored by interferon (IFN)‐γ ELISPOT and cytokine secretion assays. Moreover, these selected peptides also induced specific IFN‐γ T cell responses in blood from HPV16+ CIN2/3 and cervical carcinoma patients. We thus conclude that the identified T helper epitopes are valuable candidates for the development of a comprehensive therapeutic HPV vaccine.