Induction of a mucosal immune response will be an essential attribute of a successful vaccine to block transmission of HIV infection. Studies in the SIV animal model system have demonstrated that immune responses following mucosal exposure to viral vectors and peptides can blunt the replication and pathogenesis of SIV after infection. Viral vectors based on two members of the poliovirus and coxsackievirus have been employed in some of these studies. The use of these and similar enteroviruses is attractive, as they replicate in lower gastrointestinal tract, and are likely to produce immune responses in both the gastrointestinal and genital tracts. However, safety concerns and plans to completely curtail the circulation of poliovirus are likely to dampen enthusiasm for using these specific viruses as vaccine vectors. The parechoviruses are closely related, but biologically distinct picornaviruses that appear naturally attenuated relative to coxsackie and polioviruses strains employed to date. Of particular importance, serious complications of parechovirus have been only rarely reported, even after infection of infants. We propose to construct and complete the initial in vitro testing of a parechovirus based vaccine vector, based on strategies already employed in the successful construction of enteroviral vectors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI060463-01
Application #
6799387
Study Section
Special Emphasis Panel (ZRG1-VACC (03))
Program Officer
Shapiro, Stuart Z
Project Start
2004-03-01
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$191,458
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Miller, John P; Geng, Yongzhi; Ng, Hwee L et al. (2009) Packaging limits and stability of HIV-1 sequences in a coxsackievirus B vector. Vaccine 27:3992-4000