It is now accepted that invasive cervical cancer is caused by infection with human papillomaviruses (HPVs), and that the development of an effective vaccine would reduce the incidence of this disease. HPV virus- like particles (VLPs) and vasomeres are promising vaccine candidates, A major advantage of these immunogens is the ability to induce serum neutralizing antibodies. Results from studies performed in animals have shown that parenterally administered VLPs induce serum antibodies that provide protection against disease. We have found recently that comparable responses are induced in mice after VLP oral immunization which suggests that oral vaccination against anogenital HPV disease may be feasible. The long-term goal of this proposal is to reduce the incidence of anogenital HPV disease through the development of cost-effective and easily administered oral vaccines.
Specific aims i nclude: 1) Characterization of systemic/mucosal responses in animals following VLP/capsomere mucosal immunization. Relative immunogenicities of VLPs/capsomere of multiple HPV types will be evaluated in mice, with and without adjuvant, and using alternative mucosal routes for immunization Oral immunogenicity will also be tested in non-human primates (i.e., baboon), and efficacy will be tested in a mucosal papillomavirus challenge model (i.e., COPV). 2) Elucidation of mechanisms of VLP enteral uptake and presentation to the immune system. We will determine anatomic localization and patho of uptake of VLPs introduced into the gastrointestinal tract. 3) Development of recombinant plants for HPV vaccine delivery. HPV-11 and -16 L1 and L2 sequences will be expressed in potato; oral immunogenicity of these materials will be tested in mice. 4) Development of novel vaccine formulations. HPV VLPs containing factors that may elicit and/or enhance cellular immune responses (i.e., HPV early region gene products or genetic sequences encoding immunomodulatory factors), will be developed and tested in vitro and in vivo. Results will yield information germane to the development of cost-effective easily administered oral vaccines against invasive cervical cancer and other HPV associated diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA084105-02
Application #
6377651
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Wong, May
Project Start
2000-04-02
Project End
2004-03-31
Budget Start
2001-04-10
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$282,599
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627