#05-174

Complete

Date Full Report Received

09/26/2008

Date Abstract Report Received

09/26/2008

Investigation

Institution:
Primary Investigator:

Successful PRRSV vaccines and vaccination strategies are best employed when the host’s immune response to the pathogen is understood. Since it was generally known that PRRSV caused non-virus specific polyclonal B cell proliferation, we choose to verify and characterize this phenomenon using germfree isolator piglet so that the effect of PRRSV could only be attributed to the viral infection. We choose to address two features of the antibody response that could characterize this effect: the development of the variable region antibody repertoire (which determines specificity) and class switch recombination (CSR) that determined antibody function. Studies on repertoire development further characterized the pre-immune VH repertoire (Butler et al 2006) and we used this information to strongly confirm the non-specific polyclonal activation of pre-immune B cells (Butler et al 2007, 2008). These findings suggest that PRRSV produces or stimulates the host to produce a “B cell superantigen” that results in a massive expansion of B cells and non-specific antibodies which subvert the host’s immune system from its normal role of making effective anti-viral antibodies (Butler et al 2008). The industrial/therapeutic implication should be to encourage the production of a vaccine strain which does not cause polyclonal B cell activation but rather allows the energy of the host to be used for an anti-viral response. The second goal, to investigate CSR, has not yet shown that there is any preferential use of an IgG subclass in PRRSV-infected piglets versus littermates infected with swine influenza (SIV). Thus, the delay in an effective neutralizing response to PRRSV is unlikely to be due to CSR to a non-neutralizing IgG subclass antibody. In addressing the subclass issue, we first completed the characterization of the six IgG subclasses of swine, analyzed their predicted functional capabilities and their relative usage. The studies have generated two major publications (Butler and Wertz, 2006; Butler et al 2008) and one submitted manuscript. The importance of these studies is that they will allow future investigators to better understand the potential of the porcine IgG subclass antibodies in responding to important and emerging epizootic pathogens.