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Therapeutic/preventive vaccination against MusPV

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI112421-01
Agency Tracking Number: R43AI112421
Amount: $595,194.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA10-123
Timeline
Solicitation Year: 2015
Award Year: 2014
Award Start Date (Proposal Award Date): 2014-06-01
Award End Date (Contract End Date): 2016-05-31
Small Business Information
1448 South Rolling Road
Baltimore, MD 21227
United States
DUNS: 967536249
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 YUNG CHANG
 (410) 804-9662
 zhuxi50@gmail.com
Business Contact
 TZYYCHOOU WU
Phone: (410) 804-9662
Email: wutc@jhmi.edu
Research Institution
N/A
Abstract

DESCRIPTION provided by applicant While most human papillomavirus HPV infections are short lived a subset become chronic and can progress to malignancy with much greater frequency in HIV infected individuals Only a dozen andapos high riskandapos HPV types cause cancer but HPV alone is responsible for andgt of anal cancer head and neck cancer and of cervical cancer Further andapos low riskandapos HPV types produce considerable morbidity for HIV patients Unfortunately neither licensed HPV vaccine is effective for treatment of existing infections and persistent HPV infection and disease remain very prevalent and problematic HIV patients exhibit more chronic and progressive HPV infections than healthy individuals despite HAART and are at significantly elevated risk for HPV associated cancers Poor outcomes of HPV infection are associated with declining CD T cell immunity in HIV patients Current non specific wart treatments frequently fail Therefore our objective is to develop a therapeutic vaccine to treat chronic HPV infections in the context of HIV despite reduced CD T cell help Recently a laboratory mouse papillomavirus MusPV was discovered and sequenced Published studies suggest that MusPV infection persists in immunodeficient mice but is cleared by weeks in immune competent mice a situation that closely parallels HPV disease in patients with compromised CD T cell immunity versus healthy individuals We therefore hypothesize that compromised CD T cell immunity in mice will permit chronic MusPV infection and we propose to determine the relationship between persistence of MusPV infection and CD T cell immunity We will explore the impact of CD T cell depletion on the development of chronic MusPV infection and papillomas Several studies indicate that immunization via in vivo electroporation will improve DNA vaccine delivery and efficacy Furthermore fusion of the E and E viral oncoproteins to a heat shock protein calreticulin CRT profoundly enhances the induction of antigen specific CD T cell dependent cellular immunity even in CD T cell depleted animals Vaccination of mice with a DNA expressing CRT fused to HPV E E and capsid protein L pNGVL a CRTE E L PVX induces both antitumor immunity and L specific neutralizing antibodies We hypothesize that vaccination of CD T cell depleted mice with a MusPV version of PVX DNA via in vivo electroporation will eliminate chronic papillomavirus disease and elicit protective immunity Thus here we propose to characterize the immune response generated by in vivo electroporation of the MusPV version of PVX DNA vaccine including protection from viral challenge and its therapeutic effect against chronic MusPV infection in CD T cell depleted mice An effective treatment for HPV disease in HIV patients and the ability to protect them from diverse HPV infections remains an important unmet medical need Successful implementation of the current proposal will serve as an important foundation for future transition of the PVX DNA vaccine delivered by electroporation to clinical trials in patients with HPV neoplasia and HIV co infection PUBLIC HEALTH RELEVANCE Persistent human papillomavirus HPV infections are associated with considerable morbidity and cancer mortality worldwide and are particularly problematic in patients with HIV High risk HPV has been identified as the causative agent for of all cancers worldwide including cervical and other anogenital cancers and a subset of head and neck cancers that afflict HIV patients at higher rates HPV infection and HPV associated disease of the oral and anogenital sites are highly prevalent and commercial HPV vaccines do not impact pre existing HPV infection Thus the overall objective of our proposal is to develop a vaccine that is effective even in HIV patients for the treatment of chronic HPV infections and disease

* Information listed above is at the time of submission. *

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