Characterization of the IgA response to PRRS virus in pig oral fluids

Abstract

Porcine Reproductive and Respiratory Syndrome (PRRS) is a complex model of host/virus relationship. Disease control measures often includes "acclimatization", i.e. the exposure of PRRS-naïve gilts and sows to PRRSV-infected pigs and premises before the breeding period. In this respect, we had repeatedly observed an association between PRRSV-specific IgA responses in oral fluids (OF) of gilts and block of PRRSV spread. Therefore, we set out to investigate in vitro the inhibition of PRRSV replication by OF samples with different titers of PRRSV-specific IgA and IgG antibody, using Real-time RT PCR. PRRSV yield reduction in monocyte-derived macrophages was associated with the IgA content in OF samples, whereas the IgG-rich samples were sometimes associated with antibody-dependent enhancement (ADE) of replication. Accordingly, we could discriminate between ADEpositive and ADE-negative PRRSV strains. Next, we separated Ig isotypes in OF samples of PRRSV-infected pigs by means of protein A and size exclusion chromatography. The above results were confirmed by using separated Ig isotypes. Both dimeric and monomeric IgA were associated with the strongest reduction of PRRSV replication. The treatment of pig macrophages with separated OF antibodies before PRRSV infection was also associated with PRRSV yield reduction, along with clear changes of both CD163 and CD169 surface expression. Our results point at a role of mucosal IgA in the control of PRRSV replication by extra-and/or intracellular interaction with PRRSV, as well as by induction of signals leading to a reduced susceptibility of macrophages to PRRSV infection.

Reappraisal of PRRS Immune Control Strategies: The Way Forward

“…Is the “acclimatization” of sows and gilts based on a peculiar form of “trained immunity”? On the whole, as reported in a recent study of ours [ 87 ], the emerging picture in the PRRS model outlines unusual effector roles of adaptive immunity: both IgA Ab and cell-mediated immune responses (IFN-γ SCs) can coincide for a major modulation of macrophage permissiveness to PRRSV, as a foundation of disease control. Finally, immunomodulation by oral, low-dose IFN-alpha treatments has shown some efficacy vis-à-vis field PRRS outbreaks [ 4 ]; the peculiarities of this approach have been evaluated in a recent review paper of ours [ 111 ].…”

“…Therefore, the presence of IgA-PRRSV complexes is conducive to the control of PRRSV infection, whereas IgG-PRRSV complexes may even be associated with ADE [ 79 ]. Accordingly, OF samples with moderate IgA Ab titers for PRRSV cause a yield reduction of PRRSV replication in MO cultures, as opposed to OF samples with little, if any, IgA antibodies to PRRSV [ 87 ]. Interestingly, a balance in OF between the IgG and IgA antibody response to PRRSV was not observed over several weeks in PRRS-unstable herds experiencing overt clinical cases; once a balance is observed, virus shedding in OF comes to an end, despite the ongoing viremia [ 86 ].…”

Reappraisal of PRRS Control Strategies: The Way forward

“…Is "acclimatization" of sows and gilts based on a peculiar form of "trained immunity"? On the whole, as reported in a recent study of ours [86], the emerging picture in the PRRS model outlines unusual effector roles of adaptive immunity: both IgA Ab and cell-mediated immune responses (IFN-g SCs) can concur to a major modulation of macrophage permissiveness to PRRSV, as a foundation of disease control. Finally, immunomodulation by oral, low-dose IFN-alpha treatments has shown some efficacy vis-à-vis field PRRS outbreaks [4]; the peculiarities of this approach have been evaluated in a recent review paper of ours [110] .…”

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2

“…Although no viremia was detected in the blood of animals that received nAbs (1:32), they transmitted the virus during the last 5 of 14 days post-infection, suggesting that locally produced nasal and salival antibodies are also needed ( 130 ). In this regard, dimeric and monomeric salival IgA isolated from farm animal samples reduced PRRSV-2 macrophage infection in vitro more efficiently than IgG ( 131 ).…”