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National Vaccine Program Office
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Proposal Number: | C6 |
PI Name: | Tripp, Ralph A., Anderson, Larry J. |
PI Email: | |
PI Title: | Supervisor |
Project Title: | Characterization of the CX3C chemokine-like region in the G glycoprotein of respiratory syncytial virus. |
Project Start: | 2003 |
Project End: | 2004 |
Abstract: Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract disease in infants and adolescents, and is an important pathogen in the elderly and immune compromised patient. Currently no safe and efficacious RSV vaccine is available in part due to an incomplete understanding of the mechanisms of immunity and disease pathogenesis associated with RSV infection. Of the 11 viral proteins encoded by the RSV genome, only the F and G glycoproteins induce neutralizing antibodies and long-term protective immunity; therefore, these glycoproteins are being considered as vaccine candidates. The F glycoprotein induces the highest levels of protective immunity, while the G glycoprotein appears to be also linked to pathogenesis of RSV disease. Recent evidence from our laboratory has shown that the G glycoprotein contains a functional CX3C chemokine motif that acts as an antagonist for the only known CX3C chemokine, fractalkine, and appears to use the fractalkine receptor, CX3CR1, to facilitate infection. These results indicate that the CX3C region is important in the biology of RSV infection and suggest new directions for developing RSV vaccines. The objectives of the proposal are to characterize G glycoprotein binding to CX3CR1 and identify associations between CX3C-CX3CR1 blocking antibodies and protection from disease. Preliminary examination of human sera specimens from candidate RSV vaccine trials suggest that protection from symptomatic RSV disease associated with vaccination is linked with inhibition of G glycoprotein binding to CX3CR1 and G glycoprotein-mediated leukocyte chemotaxis. A better understanding of the impact of RSV vaccination and inhibition of G glycoprotein CX3C-CX3CR1 interaction may facilitate RSV vaccine development and lead to new approaches to limit RSV infection and disease pathogenesis.
Institution: Centers for Disease Control and Prevention
Date: July 2003
Last revised: January 13, 2004
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