Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

Abstract

Many highly effective vaccines have been produced against viruses whose virulent infection elicits strong and durable protective immunity. In these cases, characterization of immune effector mechanisms and identification of protective epitopes/immunogens has been informative for the development of successful vaccine programs. Diseases in which the immune system does not rapidly clear the acute infection and/or convalescent immunity does not provide highly effective protection against secondary challenge pose a major hurdle for clinicians and scientists. Porcine reproductive and respiratory syndrome virus (PRRSV) falls primarily into this category, though not entirely. PRRSV causes a prolonged infection, though the host eventually clears the virus. Neutralizing antibodies can provide passive protection when present prior to challenge, though infection can be controlled in the absence of detectable neutralizing antibodies. In addition, primed pigs (through natural exposure or vaccination with a modified-live vaccine) show some protection against secondary challenge. While peripheral PRRSV-specific T cell responses have been examined, their direct contribution to antibody-mediated immunity and viral clearance have not been fully elucidated. The innate immune response following PRRSV infection, particularly the antiviral type I interferon response, is meager, but when provided exogenously, IFN-α enhances PRRSV immunity and viral control. Overall, the quality of immunity induced by natural PRRSV infection is not ideal for informing vaccine development programs. The epitopes necessary for protection may be identified through natural exposure or modified-live vaccines and subsequently applied to vaccine delivery platforms to accelerate induction of protective immunity following vaccination. Collectively, further work to identify protective B and T cell epitopes and mechanisms by which PRRSV eludes innate immunity will enhance our ability to develop more effective methods to control and eliminate PRRS disease.

Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination

“…The development of neutralising antibodies (NA) and/or of a cell-mediated immunity (CMI) have been related with the clearance of PRRSV infection or pre-exposure protection [23, 59–63]. Nevertheless, since viraemia can be resolved without the development of neutralising antibodies or strong CMI, the correlates of protection are still not well understood [64–68]. In addition, the genetic/antigenic diversity of PRRSV and the idiosyncrasy of each individual are also known to play a role.…”

The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I

“…PRRSV infection in pigs typically induces an impaired immune response in the host including a weak innate immunity (Albina et al, 1998), a delayed neutralizing antibody response (Loemba et al, 1996;Yoon et al, 1994), and a gradual slow development of cell-mediated immune (CMI) responses (Loving et al, 2015;Meier et al, 2003). The same scenario also applies to the PRRSV modified live-attenuated vaccine (MLV)-induced immunity (Meier et al, Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/yviro 2003).…”

“…It is frequently observed that PRRSV-specific IFNγ-secreting cells were not detected in pigs until 2 À 3 weeks either post-infection or post-vaccination, and their frequency in peripheral blood increased slowly afterwards and remained at low levels (Loving et al, 2015;Meier et al, 2003). It is also reported that PRRSV infection reduced the surface expression of Swine Leukocyte Antigen class I (SLA-I) in macrophages and dendritic cells (Park et al, 2008;Wang et al, 2007).…”

Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-15 through PKCβ1-TAK1-NF-κB signaling pathway

“…Interestingly, we detected IL-15 mRNA level in PBMC at 7, 10, and 14 days after PRRSV-infected pigs (data not shown), finding that IL-15 was slightly up-regulated (about 2 fold) at 7 days after PRRSV-infected pigs, but IL-15 was suppressed at 10 and 14 days after PRRSV-infected pigs. The downexpression of IL-15 might have an effect on the suppressed NK cell cytotoxicity and the delayed low virus-specific CD8 þ T-cell response (Ferrari et al, 2013;Loving et al, 2015). In addition, IL-15 is not the only cytokine to regulate the antiviral function of NK cells and CD8 þ T cell immune response, and IFNα/β, IL-12 and other cytokines also coordinately participate in the regulation of NK cell function and CD8 þ T cell activities during viral infections (Ivashkiv and Donlin, 2014;Nguyen et al, 2002).…”