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Development of human papillomavirus (HPV) vaccines for prevention and treatment of cervical cancer

Objective

The overall objective is to provide scientific background for the development of efficient and safe prophylactic and therapeutic HPV-specific vaccines.

* To study the prevalence and rate of infection of HPV 16 and HPV58 in high-risk areas for cervical cancer in China
* To develop recombinant vaccines for prevention of HPV16 and 58 infections by eliciting L1-specific neutralizing antibody response
* To develop recombinant therapeutic vaccines based on modified E6 and E7 of HPV16 and 58 capable of effectively inducing cytotoxic T lymphocyte (CTL) response against HPV16 and 58-infected pre-malignant and malignant cells.
Expected Outcome

The study will also assess the incidence and prevalence of HPV infection and to estimate the statistical power of future vaccination trial with the HPV L1 vaccine in high-risk groups for human cervical cancer.
To collect serum samples from approximately 1000 individuals of 15 to 35 years of age in a high-risk area for human cervical cancer to determine antibody titer against HPV 16 and 58. Serum samples from the same 1000 individuals will be taken one year later in order to estimate incidence and prevalence rate. HPV 16 and 58 virus-like particles (VLPs) will be used as the antigens to develop HPV-specific ELISA.

Chimeric virus-like particles (CVLPs) consisting of HPV16 L1 protein fused to mutated E6 or E7 will be made and used as the vaccines. The serological and CTL responses to these CVLPs will be evaluated in mice.

HPV58 L1 gene will be cloned and inserted into expression vector in vaccine strain, replication-deficient vaccinia virus. Serum IgG antibody response upon systemic immunization and IgA antibody response upon mucosal immunization will be measured. Efficacy of vaccination will also be examined by HPV58 epithelial infection.

HPV58 E6,E7 genes will be cloned and modified by site-directed mutagenesis. The loss of their transforming activities will be checked by in vitro transformation assay. The mutated HPV58 E6,E7 genes will be cloned to vaccinia viral vector serving as the therapeutic vaccine. CTL responses will be monitored and their activities against HPV58+ tumour cells grown in vivo will be examined.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Chinese Academy of Medical Sciences
Address
Pan Jia Yuan
100021 Beijing
China

Participants (4)

Chinese Academy of Preventive Medicine
China
Address
100,Ying Xin Jie
100012 Bei-jing
KAROLINSKA INSTITUTE
Sweden
Address
13,Nobels Väg 16
171 77 Stockholm
MediGene - Gesellschaft für Molekularbiologische Diagnostik, Therapie und Technologie mbH
Germany
Address
11,Lochhamer Strasse
82152 Martinsried Bei München
Stiftung Deutsches Krebsforschungszentrum
Germany
Address
280,Im Neuenheimer Feld
69120 Heidelberg