The recent development of prophylactic vaccines protective against ?high risk? human papillomaviruses (HPV) is a landmark in medicine. The current vaccines are composed of recombinant virus-like particles (VLPs) of the major capsid protein, L1, including the high-risk HPV types 16 and 18. Phase II/III clinical trials have shown >95% efficacy of these VLP preparations in preventing HPV 16, 18 infection, and thus hopefully preventing the eventual development of about 70% of cervical cancers associated with these types. Despite this success the VLP vaccines have the adverse attributes of high cost ($360 for the initial three immunizations in the USA) and a requirement for refrigeration (i.e., cold chain). We have previously characterized the immunogenic properties of VLP subunits, pentameric L1 capsomeres. Capsomeres can be purified after recombinant expression of L1 in E. coli as untagged native proteins, at levels suggesting a significant reduction in manufacturing expense. The purified protein can be freeze-dried, resuspended, and stored at room temperature without loss of immunogenicity. Capsomeres have been suggested as a ?next generation? HPV vaccine that might be ideally suited for production and use in underdeveloped countries of the world where cervical cancer is particularly prevalent. We propose to use an HPV16 L1 capsomere protein that has been GMP produced (BioSidus, S.A.), vialed, and toxicology screened for study in a phase I human trial.
In Aims 1 and 2 we propose a dose escalation scheme of 15 subjects at each of three dose levels (10, 50, 250 micrograms), repeated three times, with concomitant analysis of toxicity, development of neutralizing antibodies, and cytotoxic T-cell responses. In the third aim, laboratory and animal experiments will test new vaccine formulation strategies, and evaluate the possibility that capsomere vaccines may be prepared as powders with adjuvants, which are thermostable

Public Health Relevance

The results of this project will determine whether capsomere vaccine preparations can proceed to further testing in a quadrivalent heat-stable formulation; under the auspices of the NCI PREVENT program. The goal is the development of a next generation HPV vaccine that is economically feasible for production and use in the underdeveloped world where the impact of cervical cancer on women?s health is greatest.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA098252-11
Application #
8747837
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (M1))
Project Start
2003-09-30
Project End
2019-08-31
Budget Start
2014-09-24
Budget End
2015-08-31
Support Year
11
Fiscal Year
2014
Total Cost
$242,977
Indirect Cost
$49,361
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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