The status of HPV16-speciﬁc T-cell reactivity in health and
disease as a guide to HPV vaccine development
Sjoerd H. van der Burg *, Annemieke de Jong, Marij J.P. Welters,
Rienk Offringa, Cornelis J.M. Melief
Tumor Immunology Group, Department of Immunohematology and Blood Transfusion, University Medical Center, Albinusdreef 2, 2333
ZA Leiden, The Netherlands
Human papilloma viruses (HPV) are among the most common sexually transmitted pathogens in young adults. In
the majority of individuals, anti-viral immunity is capable of suppressing viral infection but in a minority of patients
viral infection is not cleared in time to prevent the development of malignancies. In these cases, HPV16-specific
immunity may develop too late, is not strong enough, and/or is possibly of the wrong type. The influence of pre-existing
immunity on the efficacy of vaccines is largely unknown. Nor has it been studied what the effect is of vaccines on the
various types of pre-existing HPV-specific T-cell immunity. Animal models showing that vaccines are able to protect
against a subsequent tumor challenge and even to treat transplantable tumors, are not qualified to address this point
because tumor development is not preceded by persistent viral infection. Therefore, the comparison between fully
characterized pre-existing HPV-specific immunity in patients and healthy subjects is a prerequisite for the full
appreciation of vaccine-efficacy as well as for further development of next-generation vaccines.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: HPV; T-cell immunity; Vaccine
1. Introduction: vaccine development in relation to
pre-existing HPV16-induced immunity
The oncogenic types of human papilloma virus
(HPV) cause several types of human cancer, in
particular cervical carcinoma (zur Hausen, 1996).
HPV16 DNA is detected in !
50% of all cervical
tumors and the expression of HPV16 derived E6
and E7 onco-proteins is essential for maintaining
the transformed state. The manifestation of these
viral antigens lies at the basis of the development
of therapeutic vaccines for the treatment of
HPV16-induced lesions. Candidate vaccines, tar-
geting these viral antigens, were able to induce
effective HPV16-specific T-cell responses that
protected mice against a subsequent HPV16'
* Corresponding author. Tel.: '
31-71-526-4007; fax: '
E-mail address: firstname.lastname@example.org (S.H. van der
Virus Research 89 (2002) 275 Á
0168-1702/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
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