International Immunology Advance Access originally published online on December 27, 2004
International Immunology 2005 17(2):167-176; doi:10.1093/intimm/dxh197
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© 2004 The Japanese Society for Immunology
Epitope specificity and longevity of a vaccine-induced human T cell response against HPV18
1 Section of Infection and Immunity, Wales College of Medicine, Cardiff University, Henry Wellcome Research Building, Heath Park, Cardiff CF14 4XX, UK
2 Department of Obstetrics and Gynaecology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XX, UK
Correspondence to: S. Man; E-mail: mans{at}cf.ac.uk
Persistent human papillomavirus (HPV) type 16 and 18 infection can lead to pre-malignant and malignant diseases of the lower genital tract. Several lines of evidence suggest that T cell responses can control HPV infection. However, relative to other human viruses, strong effector memory T cell responses against HPV have been difficult to detect. We used an in vitro stimulation step prior to enzyme-linked immunospot assays to identify IFN-
-secreting T cells specific for HPV16 and 18 E6/E7 peptides. This allowed the detection of HPV-specific CD4+ T cells that were not evident in direct ex vivo assays. T cell responses against HPV16 or 18 peptides were detected in healthy volunteers (7/9) and patients with lower genital tract neoplasia (10/20). Importantly, this assay allowed tracking of vaccine-induced T cell responses in nine patients, following inoculation with a live recombinant vaccinia virus (HPV16 and 18 E6/E7, TA-HPV). Novel vaccine-induced T cell responses were demonstrated in five patients, but no clinical responses (lesion regressions) were seen. For one vaccinated patient, the T cell response was mapped to a single dominant HPV18 E7 epitope and this response was sustained for >3 years. Our data suggest that systemic memory T cells against HPV16 and 18, induced naturally or by TA-HPV vaccination, are relatively rare. Nevertheless, the assay system developed allowed estimation of magnitude, epitope specificity, and longevity of vaccine-induced CD4+ T cell responses. This will be useful for vaccine design and measurement of immunological endpoints in clinical trials.
Keywords: ELISPOT, papillomavirus, vaccinia virus
Transmitting editor: E. Simpson
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