Antigenic profiling of the porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in sows and boars, and is involved in the porcine respiratory disease complex, causing huge economical losses to the swine industry. Despite the development and broad implementation of vaccines, the virus could not be eradicated, and the high variability and fast evolution of the virus compromises the efficacy of the current vaccines in the field. Since PRRSV engages a complex interaction with the host’s immune system, and exploits several strategies to evade protective immunity, the development of new and better PRRSV vaccines is highly relying on a good understanding of the virus-specific immune response. The general goal of this work was to create new insights into one particular hallmark of PRRSV-specific immunity, namely the weak virus-neutralizing antibody response upon infection or vaccination in pigs, in sharp contrast with the robust non-neutralizing antibody response. Chapter 1 summarizes the current literature on general aspects of the virus and the disease, PRRSV-specific immunity, and PRRSV vaccines. Furthermore, the current knowledge on the PRRSV-specific neutralizing antibody response is extensively discussed. In Chapter 2, the particular problem underlying the work in this thesis is described, and a number of aims are stated. The next two chapters consist of research results addressing these aims. In Chapter 3, it was investigated to which extent virus-neutralizing antibodies can be induced by immunization of pigs with inactivated PRRSV. This study addresses the question whether the poor development of virus-neutralizing antibodies is dependent on structural properties of the virus, or rather on replication-dependent mechanisms. Experimental vaccines were produced, based on formerly optimized virus inactivation procedures and by using a number of different adjuvants. Vaccination of PRRSV-negative piglets systematically led to a strong virus-specific antibody response, but the virus-neutralizing antibody response was very weak or absent, indicating that the poor immunogenicity of neutralizing antibody targets in PRRSV is to a large extent inherent to the structural properties of the virus. Still, vaccination with a high dose of inactivated PRRSV in combination with one particular adjuvant induced virus-neutralizing antibodies, and provided a certain level of protection against viremia upon infection. These results formed the basis for further vaccine research at the Laboratory of Virology. Chapter 4 deals with the identification of non-neutralizing and neutralizing antibody targets in the European prototype PRRSV strain Lelystad virus (LV). In a first study (§ 4.1), the antibody response against linear epitopes in the GP4 protein was investigated. It was found that antibodies are to a large extent produced against one particular region of this protein that was earlier described as neutralizing antibody target. Since this region is highly variable, the antibody response against GP4 was also investigated for other virus strain. The conclusion of this study was that the variable region in GP4 of EU-type PRRSV induces neutralizing antibodies upon infection in pigs, but only against strictly homologous virus. In a second study (§ 4.2), the antibody response against the entire set of envelope proteins (GP2, E, GP3, GP4, GP5 and M) upon infection with LV was investigated. Twenty-one antigenic regions were identified that are capable of inducing antibodies in pigs. Peptide-purified antibodies against four antigenic regions turned out to reduce in vitro virus replication. In addition to the known neutralizing epitope in GP4, two neutralizing antibody targets were identified in GP2, and one in GP3. No neutralizing epitopes were found in E, GP5 and M. Since the neutralizing epitope in GP3 was one of the more immunogenic regions, the antibody response against this epitope was investigated more extensively in different virus strains. Taken together, it can be concluded from Chapter 4 that four linear neutralizing antibody targets are present in the LV envelope proteins: two weakly immunogenic epitopes in GP2, one more immunogenic epitope in GP3, and one strongly immunogenic but highly variable epitope in GP4. Chapter 5 provides a general discussion on the research data generated in this thesis. In § 5.1, it is discussed what can be learned from the vaccination studies in Chapter 3. § 5.2 summarizes the results from Chapter 4, and discusses them in a broader context. First, a synoptic visual overview is given of the non-neutralizing and neutralizing antibody targets that were identified in the viral envelope proteins. Next, some hypotheses are presented on how neutralizing antibodies against different parts of the viral proteins may interfere with viral replication. Subsequently, the current knowledge on PRRSV antigenicity is discussed in light of virus evolution, and some thoughts are made on how the high mutation rate and large variability of the virus may be involved in immune evasion. To conclude, it is critically evaluated to which extent the data generated in this thesis can contribute to the development of new and better PRRSV vaccines.

Grantor dc:publisher

Ghent University. Faculty of Veterinary Medicine

Year dc:date

2011

Author dc:creator

• Vanhee, Merijn

Contributors dc:contributor

• Nauwynck, Hans

• Veterinary Sciences
• Epitope
• Porcine reproductive and respiratory syndrome virus
• Antigenic profiling
• Antibody
• Vaccine

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://biblio.ugent.be/publication/1864156
urn:isbn:9789058642646
https://biblio.ugent.be/publication/1864156/file/4335638

OAI identifier oai:identifier

oai:archive.ugent.be:1864156