Immune Control of PRRS: Lessons to be Learned and Possible Ways Forward

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is an elusive model of host/virus relationship in which disease is determined by virus pathogenicity, pig breed susceptibility and phenotype, microbial infectious pressure, and environmental conditions. The disease can be controlled by farm management programs, which can be supported by vaccination or conditioning of animals to circulating PRRS virus (PRRSV) strains. Yet, PRRS still represents a cause of heavy losses for the pig industry worldwide. Immunological control strategies are often compounded by poor and late development of adaptive immunity in both vaccinated and infected animals. Also, there is evidence that results of field trials can be worse than those of experimental studies in isolation facilities. Neutralizing antibody (NA) was shown to prevent PRRSV infection. Instead, the role of NA and adaptive immunity on the whole in virus clearance after established PRRSV infections is still contentious. Pigs eventually eliminate PRRSV infection, which may be correlated with an “educated,” innate immune response, which may also develop following vaccination. In addition to vaccination, an immunomodulation strategy for PRRS can be reasonably advocated in pig “problem” farms, where a substantial control of disease prevalence and disease-related losses is badly needed. This is not at odds with vaccination, which should be preferably restricted to PRRSV-free animals bound for PRRSV-infected farm units. Oral, low-dose, interferon-α treatments proved effective on farm for the control of respiratory and reproductive disease outbreaks, whereas the results were less clear in isolation facilities. Having in mind the crucial interaction between PRRSV and bacterial lipopolysaccharides for occurrence of respiratory disease, the strong control actions of low-dose type I interferons on the inflammatory response observed in vitro and in vivo probably underlie the rapid clinical responses observed in field trials.

In vitro Cytokine Responses to Virulent PRRS Virus Strains

“…These data are in agreement with the murine Arterivirus model, in which the infection shows the same time course in both immunotolerant and control mice (8). Finally, the clinical features observed experimentally in isolation facilities are often quite different from those found in field cases (9), which points at a major role of environmental, infectious, and non-infectious stressors in the onset of full-blown clinical disease (10). The same discrepancy between field and isolation facilities also refers to inactivated and attenuated PRRS vaccines, the impact of which may be sometimes worse than expected on farm (11).…”

“…Yet, a robust, coherent view of the molecular basis of PRRSV virulence is still lacking. PRRSV pathogenicity seems to be crucially affected by genetic features of the virus, genetic features of the host ( 26 ), and environmental, infectious, and non-infectious stressors ( 10 ). PRRSV circulated for decades in Eastern Europe ( 23 ) without causing disease, which appeared after the reunification of Germany in 1990, when PRRSV met the lean type, fast-growing pigs reared in western Europe.…”

Innate immune responses induced by the saponin adjuvant Matrix-M in specific pathogen free pigs

“…Experience from porcine reproductive and respiratory syndrome virus [22] and PCV2 [51] demonstrate that infectious diseases in production animals are often multifactorial and may benefit from stressors such as weaning, transport and mixing of groups [21]. In an effort to imitate field conditions, SPF pigs were subjected to non-infectious stress from transport and mixing of groups and to infectious stress by contact exposure to conventionally reared pigs (Figure 1).…”

“…Physiological stress and infectious agents co-operate and preventive treatments include administration of IFN-α [22, 23] and β-glucans [24, 25]. Immunomodulators as a tool to boost the immune system against possible infections can potentially also be used in emergency vaccines [26].…”

Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV)

“…As a whole, neutralizing antibodies and PRRSV-specific IFN-γ secreting cells do not fully depict the immune effector functions related to protective immunity, as the viral targets related to them are unknown. As a consequence, correlates of protection remain elusive for this infection due to the laborious work in vitro and in vivo and the enormous genetic diversity that causes confusion and makes it difficult to predict how immune responses against one isolate or strain could be applied to another in a cross-protective immune prediction model (103, 104). Without any doubt, the most important gap of knowledge for PRRSV is the lack of correlates of protection that makes extremely difficult to have robust models to check vaccines efficacy against this disease (Box 1).…”