The overall goal of this proposal is develop a novel method for HIV vaccine development. The hypothesis which is set forth is as follows: that bacteriophage vectors can be adapted for delivery of exogenous genes to mammalian cells, including dendritic cells, and that these modified bacteriophage vectors can be used to elicit specific and potent antiviral cytotoxiclymphocyte (CTL) responses to an encoded HIV-1 antigen. This hypothesis will be tested as follows: genetically modified phage vectors will be constructed, and their ability to elicit HIV-specific CTL responses will be examined using a small animal model system. Overall, the work is expected to contribute to the development of phage vectors suitable for use in HIV vaccine delivery. Such vectors would be simple to use, cheap to manufacture and considerably safer than vectors based on potentially pathogenic human or animal viruses. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI054330-02
Application #
6700014
Study Section
Special Emphasis Panel (ZRG1-SSS-C (29))
Program Officer
Hernandez, Milton J
Project Start
2003-02-01
Project End
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
2
Fiscal Year
2004
Total Cost
$41,161
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Santos, Kathlyn; Sanfilippo, Christine M; Narrow, Wade C et al. (2007) Infectivity of herpes simplex virus type-1 (HSV-1) amplicon vectors in dendritic cells is determined by the helper virus strain used for packaging. J Virol Methods 145:37-46
Lankes, H A; Zanghi, C N; Santos, K et al. (2007) In vivo gene delivery and expression by bacteriophage lambda vectors. J Appl Microbiol 102:1337-49
Santos, Kathlyn; Duke, Cindy M P; Rodriguez-Colon, Sol M et al. (2007) Effect of promoter strength on protein expression and immunogenicity of an HSV-1 amplicon vector encoding HIV-1 Gag. Vaccine 25:1634-46
Santos, Kathlyn; Simon, David A L; Conway, Erin et al. (2007) Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors. Hum Gene Ther 18:93-105
Santos, Kathlyn; Duke, Cindy M P; Dewhurst, Stephen (2006) Amplicons as vaccine vectors. Curr Gene Ther 6:383-92
Gorantla, Santhi; Santos, Kathlyn; Meyer, Vakara et al. (2005) Human dendritic cells transduced with herpes simplex virus amplicons encoding human immunodeficiency virus type 1 (HIV-1) gp120 elicit adaptive immune responses from human cells engrafted into NOD/SCID mice and confer partial protection against HIV-1 chal J Virol 79:2124-32