Porcine reproductive and respiratory syndrome virus (PRRSV): Immunization strategies, virulence of various isolates, and efficacy of DNA vaccination.

摘要

Many different strategies have been pursued by researchers in the quest for control and ultimately the eradication of porcine reproductive and respiratory syndrome (PRRS). Some of the strategies have lead to the licensure of commercial products while others have provided insight into the biology of porcine reproductive and respiratory syndrome virus (PRRSV). Many of the strategies examined here have contributed to the overall understanding of the host's immune response to PRRSV. Some strategies have provided unconventional or in some cases controversial methods of protecting swine from PRRS. The main area of interest in this review will be the clinical protection of swine from virulent PRRSV challenge. Gross lung pathology and viremia along with virus neutralizing antibody titers will serve as the primary parameters for protection in the respiratory challenge model, whereas the number of live born pigs and the number of weaned pigs along with piglet viremia will serve as the primary parameters for protection in the reproductive challenge model. Despite the incomplete reporting of these primary parameters, some publications will be discussed that have focused on protection against PRRSV by either evaluating the immune responses in non-target animals or studies conducted in swine, some without a virulent challenge. It is important to note that for the purposes of this thesis a homologous PRRSV challenge will be defined as a challenge with the same viral isolate from which the vaccine was derived, and a heterologous PRRSV challenge will be defined as a challenge with a PRRSV isolate that is not the isolate from which the vaccine was derived. After evaluating the strategies based on these parameters the only immunization strategy that has provided efficacy against both a homologous and a heterologous challenge is the modified live vaccine.;Although much research has been performed on PRRSV, little quantitative information is available on the relationships between virulence and in vivo virus replication, among isolates recovered at different times in the history of PRRS, or the relative levels of virulence associated with individual virus isolates. In this study the in vivo growth properties of virulent field isolates and attenuated PRRSV isolates were compared. The results show that virulent PRRSV isolates exhibit longer and more elevated levels of viremia, induce faster and more intense humoral immune responses, negatively affect body weight gain, induce higher death rates, and cause more severe clinical signs in a respiratory disease model. We found that the more virulent field isolates grew to significantly higher levels in pigs than did cell-culture adapted isolates. We concluded that the pathogenic consequences and immunological responses of pigs to PRRSV are directly related to viral load in acute infection as reflected in viral titers in blood.;PRRSV causes an economically important swine disease and is an elusive target for vaccine development. Two prototype PRRSV DNA vaccines were investigated; with expression either driven by the muscle-specific synthetic SPc5-12 promoter, or by the ubiquitous CMV promoter constitutively. IngelvacRTM PRRS MLV, a commercially available modified-live virus (MLV) vaccine, served as a positive vaccination control. Both DNA vaccines significantly reduced the level of lung lesions after virulent PRRSV challenge when each group was compared to the challenge control group. The MLV provided the best level of efficacy and significantly reduced the lung lesions as compared to all other challenged groups. The level of efficacy provided by the SELI method of DNA vaccination validates this vaccination concept and allows for more focused efforts on determining the most relevant immunogenic regions of the PRRSV.