ANTI-IDIOTYPIC ANTIBODY VACCINES FOR HPV INFECTION

Project: Research project

Description

Human papillomavirus (HPV) gene products are present in most cervical and
many anogenital carcinomas. The early lesions caused by these viruses
have been shown to progress to carcinomas in some individuals, which
demonstrates that certain HPV types play a role in the development of
these tumors. A vaccine for protection against HPV infection therefore
may decrease the incidence of cervical and anogenital cancers. Such a
vaccine is currently unavailable. Our long-term goal is to develop monoclonal anti-idiotypic antibodies
(anti-Ids) that antigenically mimic neutralizing epitopes on HPVs and
which stimulate a host protective response against HPV infection. The
Specific Aims are to use sets of monoclonal antibodies which neutralize
HPV type 11 (HPV-11) and cottontail rabbit papillomavirus (CRPV) as
antigen to develop a panel of monoclonal anti-Ids. These monoclonal
anti-Ids will be tested as (i) immunogens in rabbits and mice for the
induction of virus-neutralizing antibodies, and (ii) as probes for the
detection of neutralizing antibodies in virus-infected humans and
rabbits. We will use two papillomavirus animal model systems for these studies.
The athymic mouse xenograft system utilizing HPV-11 infected human
foreskin tissue will be used as a model for infection by a human genital
papillomavirus type. The CRPV/domestic rabbit system will be used as an
animal model which allows for controlled immunizations and deliberate
viral challenge; neither of which are possible in the xenograft system.
The two papillomavirus models will provide complementary positive and
negative control reagents in the form of non-cross-reactive neutralizing
and anti-Id monoclonal antibodies for each viral system. This is because
these two viruses are host specific in their infectivity, and because the
neutralizing epitopes as detected by antibodies are virus-specific.
StatusFinished
Effective start/end date9/30/929/29/95

Funding

  • National Institutes of Health
  • National Institutes of Health: $124,118.00
  • National Institutes of Health

Fingerprint

Papillomavirus Infections
Vaccines
Anti-Idiotypic Antibodies
Cottontail rabbit papillomavirus
Monoclonal Antibodies
Human papillomavirus 11
Viruses
Neutralizing Antibodies
Heterografts
Epitopes
Antibodies
Rabbits
Carcinoma
Nude Mice
Uterine Cervical Neoplasms
Immunization
Animal Models
Incidence
Infection
Genes