Contribution of Porcine Reproductive and Respiratory Syndrome Virus Minor Glycoproteins to the Induction of a Protective Immune Response

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen affecting most swine producing countries. With costs associated with PRRSV losses and the prevention of PRRSV reaching upwards of one billion dollars per year in the United States alone, PRRSV is the most economically significant swine pathogen of the last three decades. The widespread distribution of PRRSV and the diversity of the virus, as well as the lack of a broadly protective vaccine, have made PRRSV difficult to control. The protective epitopes that are targeted by the host immune response remain poorly understood and this is an area of PRRSV research that could have a large impact on the development of a broadly protective vaccine. Proteins that interact with the host cell receptors and determine cell tropisms are of particular interest because such proteins have the potential to have conserved epitopes. In the case of PRRSV, the minor glycoprotein heterotrimer composed of GP2, GP3, and GP4, interacts with the major cellular receptor for PRRSV. The objective of this dissertation was to characterize the role of the minor glycoproteins of PRRSV in the induction of protective immunity. Heterologous prime-boost immunization with GP3 expressed in viral vectors was able to induce the production of specific antibodies and an anamnestic response after challenge, but this translated to minimal protection in vivo. The generation of a PRRSV-1/PRRSV-2 chimeric virus, expressing the minor glycoproteins of a PRRSV-2 strain in a biologically relevant form, was able to induce neutralizing antibodies and GP2, GP3, and GP4 specific T cell responses which provided partial protection against challenge with the PRRSV-2 strain. A subtractive immunization protocol in mice was utilized to further confirm the ability of the minor glycoproteins to induce the production of neutralizing antibodies. The results in this dissertation confirm that the minor glycoproteins are an important target of the protective immune response and can aid in the development of an optimal vaccine against PRRSV.