#08-193

Complete

Date Full Report Received

04/26/2010

Date Abstract Report Received

04/26/2010

Investigation

Institution:
Primary Investigator:

This study was designed to test the hypothesis that certain structural components of PRRSV drive the activation of regulatory T cells (Tregs). Activating these T cells would thereby diminish the protective immune response. The long term goal is to design vaccines containing the necessary components for producing protective immunity rather than immune suppression, and heterologous protection. This hypothesis was proposed to be tested by two objectives, only one of which was funded by this grant (the second objective will be submitted for subsequent funding). To determine which structural proteins activated Tregs, we expressed the individual structural protein open reading frames (ORF 2-7, corresponding to GP2-5, M, and N) in bacteria. We used these proteins in a Treg-activation assay in vitro to determine which structural proteins stimulate Tregs. Our results show that both GP4 and GP5 are capable of stimulating Tregs. Synthetic peptides will then be used to fine map the Treg-activation epitopes in GP4 and GP5. Activation of Tregs not only dampens the immune response to the virus and secondary infections, but may also play a role in preventing heterologous protection by vaccines. Therefore, knowing which structural proteins activate Tregs and knowing where the Treg-activation epitopes are will allow us to design vaccines that avoid a Treg-response. These vaccines will not only provide protective immunity against a homologous strain, but will confer protection against heterologous strains as well. For more information, contact Tanya LeRoith (tleroith@vt.edu).