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Research Articles: Therapeutics, Targets, and Development

Human papillomavirus type 16 L1E7 chimeric capsomeres have prophylactic and therapeutic efficacy against papillomavirus in mice

¹ Biotech Center for Viral Disease Emergency and ² Division of Hepatitis, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China

Requests for reprints: Houwen Tian, Biotech Center for Viral Disease Emergency, Yingxin Street 100, Xuanwu District, Beijing 100052, People's Republic of China. Phone: 86-10-63582045; Fax: 86-10-63552140. E-mail: houwentian{at}yahoo.com.cn and Yue Wang, Division of Hepatitis, Yingxin Street 100, Xuanwu District, Beijing 100052, People's Republic of China. Phone: 86-10-63554474; Fax: 86-10-63510565. E-mail: euy-tokyo{at}umin.ac.jp

Abstract

Genital human papillomavirus (HPV) infection is the primary cause of cervical cancer in women. Although the HPV recombinant L1 protein was recently licensed as an available vaccine, it has numerous shortcomings. New vaccination strategies should be considered. To enable the design of a prophylactic and therapeutic low-cost vaccine candidate, chimeric HPV16 L1_C34E7_N1-60 capsomeres were produced in Escherichia coli. The immune characteristics and potential prophylactic and therapeutic effects of these capsomeres were examined in C57BL/6 mice. Following protein purification and renaturation, the majority of the recombinant chimeric proteins (L1_C34E7_N1-60) assembled into capsomeres. These capsomeres were able to induce conformational and neutralizing antibodies against HPV virus-like particles and trigger cell-mediated specific immune responses against the L1 and E7 peptides. In vivo tumor challenge assays showed that mice immunized with the capsomeres were protected against a challenge with both C3 and TC-1 tumor cells. Furthermore, in vivo tumor rejection assays showed that capsomeres have therapeutic efficacy in mice following inoculation with C3 and TC-1 tumor cells. Chimeric capsomeres are capable of preventing and eliminating HPV16 infection. Therefore, our study has provided an economical vaccine candidate. [Mol Cancer Ther 2008;7(5):1329–35]

Grant support: 863 Hi-Tech Research and Development Program of China (2002AA216041).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/29/07; revised 1/22/08; accepted 2/ 4/08.