Immune response to ORF5a protein immunization is not protective against porcine reproductive and respiratory syndrome virus infection

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus responsible for PRRS in swine, a disease with globally significant animal welfare and economic concerns. There is no specific treatment and variably effective immune protection. Molecular mechanisms responsible for virulence, pathogenesis and protective immune response remain poorly understood. These factors limit progress towards development of effective measures for prevention and treatment of PRRS. A novel PRRSV ORF5a protein, encoded in an open reading frame (ORF) that overlaps the major envelope glycoprotein GP5 ORF, was recently identified. Because ORF5a is highly conserved in diverse PRRSV isolates, is a structural protein in the virion, and elicits a specific antibody response in infected pigs, we investigated its potential role in immune protection against PRRSV infection. Pigs immunized with ORF5a protein had robust serologic responses. However, the antibodies did not neutralize virus, and immunity did not protect against challenge infection. We conclude from these findings that the ORF5a antibody response is neither neutralizing nor protective.

Phylodynamic analysis of porcine reproductive and respiratory syndrome virus (PRRSV) in Italy: Action of selective pressures and interactions between different clades

“…This evidence could contribute to differential cross protection. However, evidence of the non-neutralizing role of the antibodies directed against GP5a (Robinson et al, 2013b), coupled with the purifying nature of the selection acting on this protein imposes caution when proposing the immune pressure on GP5a as one of the determinants of viral fitness.…”

Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

“…The initial investigations directed at locating neutralizing epitopes on the PRRS virion focused on the envelope glycoproteins and the M protein, which likely interact with host cell proteins and mediate viral penetration of the cell. Other structural proteins on the PRRSV envelope, such as small envelope (E) protein and the ORF5a gene product have already been ruled out as inducers of neutralizing antibodies (Robinson et al, 2013;Wu et al, 2001). Early papers reported that monoclonal antibodies specific for GP5 and GP4 (van Nieuwstadt et al, 1996) possessed PRRSV-neutralizing capacity, which led to significant investigation on these two glycoproteins as the main targets of serum NAbs, with an emphasis placed on GP5.…”

Characterization of anti-porcine epidemic diarrhea virus neutralizing activity in mammary secretions

“…The PEDV serum neutralization (SN) assay was performed essentially as described and explained (Li and Murtaugh, 2012;Robinson et al, 2013). Milk and colostrum samples were serially diluted and incubated with PEDV at a multiplicity of infection (MOI) of 0.01 for 1 h at 37 • C. Confluent Vero-81 cell monolayers in 96-well plates were washed with PBS before mixtures of sample and virus, positive-control virus and blank controls were added in duplicate.…”