Journal Article

Challenges for porcine reproductive and respiratory syndrome virus (PRRSV) vaccinology

Rebel, Johanna M.J., Moormann, Rob J., Stockhofe-Zurwieden, Norbert, Kimman, Tjeerd G., Cornelissen, Lisette A.

2009

Overview

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a threat for the pig industry. Vaccines have been developed, but these failed to provide sustainable disease control, in particular against genetically unrelated strains. Here we give an overview of current knowledge and gaps in our knowledge that may be relevant for the development of a future generation of more effective vaccines. PRRSV replicates in cells of the monocyte/macrophage lineage, induces apoptosis and necrosis, interferes with the induction of a proinflammatory response, only slowly induces a specific antiviral response, and may cause persistent infections. The virus appears to use several evasion strategies to circumvent both innate and acquired immunity, including interference with antigen presentation, antibody-mediated enhancement, reduced cell surface expression of viral proteins, and shielding of neutralizing epitopes. In particular the downregulation of type I interferon-α production appears to interfere with the induction of acquired immunity. Current vaccines are ineffective because they suffer both from the immune evasion strategies of the virus and the antigenic heterogeneity of field strains. Future vaccines therefore must “uncouple” the immune evasion and apoptogenic/necrotic properties of the virus from its immunogenic properties, and they should induce a broad immune response covering the plasticity of its major antigenic sites. Alternatively, the composition of the vaccine should be changed regularly to reflect presently and locally circulating strains. Preferably new vaccines should also allow discriminating infected from vaccinated pigs to support a virus elimination strategy. Challenges in vaccine development are the incompletely known mechanisms of immune evasion and immunity, lack of knowledge of viral sequences that are responsible for the pathogenic and immunosuppressive properties of the virus, lack of knowledge of the forces that drive antigenic heterogeneity and its consequences for immunogenicity, and a viral genome that is relatively intolerant for subtle changes at functional sites.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Allergy and Immunology / alveolar macrophages / Animals / Antigen presentation / Applied microbiology / Bacteriology / Biological and medical sciences / dehydrogenase-elevating virus / dendritic cells / Disease control / equine arteritis virus / Fundamental and applied biological sciences. Psychology / Genes / Genetic engineering / Genomes / Heterogeneity / Immune evasion / Immune response / immune-responses / Immunogenicity / major envelope proteins / Microbiology / Miscellaneous / nuclear-localization signal / Porcine Reproductive and Respiratory Syndrome - immunology / Porcine Reproductive and Respiratory Syndrome - prevention & control / Porcine reproductive and respiratory syndrome virus / Porcine respiratory and reproductive syndrome virus / Porcine respiratory and reproductive syndrome virus - immunology / Porcine respiratory and reproductive syndrome virus - pathogenicity / Porcine respiratory and reproductive syndrome virus - physiology / Proteins / Reading / reading frame 5 / recombinant pseudorabies virus / structural proteins / Swine / Vaccination / Vaccine development / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Viral Vaccines - immunology / Virology