The main goals of the Concerted Action are to develop prophylactic and therapeutic vaccines for intervention in HPV-associated disease and to develop better diagnostic and prognostic tests for HPV infections.
The Concerted Action will enable us to prepare the necessary reagents without duplication, to make the reagents available to all participants, to improve standardisation and to bring together specialists of different disciplines (like molecular biologists, immunologists and clinicians).
To be able to develop a safe and efficacious vaccine it is necessary to:
1. generate an adequate set of immunological reagents
2. standardise and improve or develop immunoassays
3. analyse the host immune response to HPV infection in animal models and test the efficacy of experimental vaccines in these models.
%Therefore, this Concerted Action has been divided into four subgroups. The tasks and activities of the subgroups, ultimately leading to a human HPV vaccine, are described below.
- Antibody group:
The humoral immune response to HPV infections ill be tested by ELISA or by immunoblot using HPV proteins or peptides. If it appears to be possible to detect specific antibodies in infected individuals or in individuals with starting and progressed CIN lesions, this assay might improve the early diagnosis of HPV infections. Furthermore this immunoassay can give clues about the role of antibodies in the protection against HPV induced CIN lesions.
- Protein group:
The aim is to examine which of the HPV genes are expressed in the different HPV-associated lesions. This information is useful for the development of a more predictive diagnostic test and for the identification of potential HPV proteins to be included in a vaccine.
The proliferative response of peripheral T-cells, T-cell lines and clones to HPV antigens will be studied. This will lead to the identification of HPV specific T-cell epitopes and the HLA restriction elements involved in the T-cell recognition. Furthermore, the functional properties of HPV-reactive T-cells to animals challenged with HPV-containing tumours will be analysed. The examination of T-cell reactivity in humans will result in the identification of those HPV T-cell epitopes that are crucial for protection in humans.
- In vivo model group:
Each participating group involved in this part of the Concerted Action has developed one or a few animal model systems for HPV, or is working with natural Papilloma Virus models (CRVP, BPV). Most of the models differ highly because different strains, cells, DNA constructs, or promoters have been used. Therefore, every model has its own advantages and limitations. Testing of promising experimental vaccines (for instance HPV-antigen expressing vaccinia and salmonella recombinants) on protection and tumour regression in several different animal models will provide, together with the data from the immunoassays, the knowledge to develop an efficacious vaccine for humans.