The Ability of Porcine Reproductive and Respiratory Syndrome Virus Isolates to Induce Broadly Reactive Neutralizing Antibodies Correlates With In Vivo Protection

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is considered one of the most relevant diseases of swine. The condition is caused by PRRS virus (PRRSV), an extremely variable virus of the Arteriviridae family. Its heterogeneity can be responsible, at least partially, of the poor cross-protection observed between PRRSV isolates. Neutralizing antibodies (NAs), known to play a role in protection, usually poorly recognize heterologous PRRSV isolates, indicating that most NAs are strain-specific. However, some pigs develop broadly reactive NAs able to recognize a wide range of heterologous isolates. The aim of this study was to determine whether PRRSV isolates that induce broadly reactive NAs as determined in vitro are able to confer a better protection in vivo. For this purpose two in vivo experiments were performed. Initially, 40 pigs were immunized with a PRRSV-1 isolate known to induce broadly reactive NAs and 24 additional pigs were used as controls. On day 70 after immunization, the pigs were divided into eight groups composed by five immunized and three control pigs and exposed to one of the eight different heterologous PRRSV isolates used for the challenge. In the second experiment, the same experimental design was followed but the pigs were immunized with a PRRSV-1 isolate, which is known to generate mostly strain-specific NAs. Virological parameters, specifically viremia and the presence of challenge virus in tonsils, were used to determine protection. In the first experiment, sterilizing immunity was obtained in three groups, prevention of viremia was observed in two additional groups, although the challenge virus was detected occasionally in the tonsils of immunized pigs, and partial protection, understood as a reduction in the frequency of viremia compared with controls, was recorded in the remaining three groups. On the contrary, only partial protection was observed in all groups in the second experiment. The results obtained in this study confirm that PRRSV-1 isolates differ in their ability to induce cross-reactive NAs and, although other components of the immune response might have contributed to protection, pigs with cross-reactive NAs at the time of challenge exhibited better protection, indicating that broadly reactive NAs might play a role in protection against heterologous reinfections.

Differences in Humoral Immune Response against the Type 2 Porcine Reproductive and Respiratory Syndrome Virus via Different Immune Pathways

“…The NAs play a crucial part in the antibody response due to their blocking of viral infection [ 34 , 35 ]. Immunosuppression can limit and delay the occurrence of NAs.…”

“…Piglets in test groups were inoculated with 10 6 TCID 50 PRRSV HeN-3 through intranasal and intramuscular inoculation (in nape) respectively, and piglets in the control group were inoculated with equal volumes of the cell culture medium. Serum and saliva in all the groups were respectively collected for viral loads and antibody titers at 0, 3,7,11,15,19,23,27,31,35,39, and 43 dpi. At 43 dpi, the PAMs, submandibular lymph nodes, and inguinal lymph nodes of piglets were obtained for viral loads detection after necropsy under clean conditions.…”

Predicting Antigenic Distance from Genetic Data for PRRSV-Type 1: Applications of Machine Learning

“…Using modified mixed-effects supervised machine learning models ( 88 ), we accounted for serum-level random effects (i.e., sera appear in multiple sera-virus pairs, and some serum may be broadly neutralizing and thus have lower apparent antigenic distances across all sera-virus pairs [ 13 ]) by adjusting the antigenic distance value by subtracting the effect of specific sera from the antigenic distance. Following Wang et al ( 88 ), we fit a general linear regression to the antigenic distance data using sera as a random effect; no fixed effects were included.…”

“…The genetic and antigenic diversity in PRRSV has greatly contributed to challenges in controlling PRRS outbreaks on farms using vaccines or live virus inoculation. Relatively suboptimal/poor cross-protection between PRRSV isolates, especially against heterologous strains, is a common issue in immunization ( 13 , 14 ), yet there are no robust criteria for defining strains as heterologous from an antigenic perspective. Thus, the classification of PRRSV strains as homologous versus heterologous predominantly relies on the characterization of viral genomes or portions of the genome to distinguish between variants (i.e., restriction fragment length polymorphisms, lineages/subtypes, or genetic distance) ( 15 – 18 ).…”

Influence of PRRSV-1 vaccination and infection on mononuclear immune cells at the maternal-fetal interface

“…Neutralizing antibodies (NAbs) occur late (about four weeks post infection) and can confer protection ( 5 , 15 ). NAbs are mostly strain specific, although heterologous NAbs have been identified ( 16 , 17 ). Interferon-γ (IFN-γ) producing T cells and NK cells are considered to be involved in protection ( 5 , 15 , 18 – 21 ).…”