Abstract
The humoral immune response plays a crucial role in the combat and protection against many pathogens including the economically most important, highly prevalent, and diverse pig pathogen PRRSV – the Porcine Reproductive and Respiratory Syndrome Virus. In addition to viremia and viral shedding analyses, this study followed the local and systemic humoral immune response of pigs for 63 days upon inoculation with one of three types of Type-2 PRRSV (PRRSV-2) strains – one modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, NC134 and NC174. The local response was analyzed by quantifying immunoglobulin (Ig)A in nasal swabs. The systemic response was studied by the quantification of IgG with ELISA and homo- and heterologous neutralizing antibodies (NAs) utilizing a novel method of flow cytometry. In all PRRSV-2 inoculated groups, viral nasal shedding started at 3 dpi, peaked between 3 and 7 days post inoculation, and was cleared at 28–35 dpi with sporadic rebounds thereafter. The local IgA response started 4–7 days after viral shedding occurred and showed a bi-phasic course with peaks at 14 dpi and at 28–35 dpi. Of note, the NC134 and NC174 strains induced a much stronger local IgA response. As reported earlier, main viremia lasted from 7 dpi to 28 dpi (NC174), 42 dpi (NC134) or until the end of the study (MLV). Similar to the local IgA response, the systemic IgG response started 4–7 days after viremia; but in contrast to viremia, serum IgG levels stayed high for all PRRSV-2 inoculated groups until the end of the study. A significant finding was that while the serum NA response in the MLV group was delayed by 28 days, serum NAs in pigs infected with our two NC134 and NC174 strains could be detected as early as 7 dpi (NC134) and 14 dpi (NC174). Compared to homologous NA responses, the NA responses against heterologous strains was strong but slightly delayed between our lineage 1 one strains or non-existent between the MLV and lineage 1 strains. This study improves our understanding of the relationship between local and systemic infections and the humoral immune response induced by PRRSV-2 infection or MLV vaccination. Our data also provide novel insights into the timeline of the development of homologous and heterologous NA levels – by both MLV vaccination or infection with two strains from the currently prevalent PRRSV-2 lineage 1.
Highlights
In addition to providing a timeline for viral shedding by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-2 strains, this study provides an overview of the humoral immune response to PRRSV-2 infections with a VR-2332based lineage 5 strain and two lineage 1 strains – NC134 and NC174 of different virulence
We show that both the local IgA
As mentioned in the introduction, these strains were selected to facilitate the study of the heterologous NA responses within currently prevalent Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-2 lineage 1 strains and across lineages between the lineage 5 modified live virus (MLV) strain and the two lineage 1 strains
Summary
Despite two decades of commercial vaccination administration to sows and nursery age pigs, Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) continues to distress the global pork industry causing significant losses globally [1, 2] through reproductive failure [3, 4], nursery age pig respiratory distress [5, 6], reduced growth [7], secondary infections [8, 9], and increased mortality [10, 11], as well as, through expenditures on vaccination and biosecurity efforts.PRRSV is divided into two distinct species: Type 1 (PRRSV1) and Type 2 (PRRSV-2) [12]; due to its RNAviral nature and propensity for genetic mutation, each type is very diverse so that numerous PRRSV strains can be described as “quasispecies” [13]. We previously characterized the complex homo- and heterologous T-cell response to a lineage 5 modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, a lowpathogenic (LP) NC134 and high-pathogenic (HP) NC174 over the course of 63 days [14] The complexity of this T-cell response seems to match the humoral immune response: The perplexing relationship between serum NAs, viremia, and protection from PRRSV is highlighted by the numerous reviews of this subject in recent years [15,16,17]. One focus of this study was the cross-reactivity of the humoral immune response induced by MLV vaccination or infection with two PRRSV-2 lineage 1 strains
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