application): Research Proposal: Development of strategies to direct immune responses toward conformation dependent neutralization epitopes is an important component of lentivirus vaccine research. This proposal addresses the hypothesis that dampening of linear immunodominant epitopes of caprine arthritis-encephalitis virus (CAEV) surface envelope glycoprotein (SU) by introduction of N-linked glycosylation sites will enhance cross-reactive neutralizing antibody responses induced by protein immunization. The CAEV model is particularly suitable to address this strategy because the immune response of infected goats is dominated by antibodies directed to linear immunodominant SU epitopes with relatively low titers of mainly type-specific neutralizing antibodies. In addition, previous studies document that (i) conformational crossreactive neutralization epitopes on oligomeric CAE virion-associated SU are exposed on soluble SU, (ii) repeated immunization with native SU induces cross reactive neutralizing antibodies, and (iii) virus neutralization is inhibited by antibodies likely directed to immunodominant linear epitopes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001790-04
Application #
6707525
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Sharma, Opendra K
Project Start
2001-03-01
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
4
Fiscal Year
2004
Total Cost
$125,280
Indirect Cost
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164