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.

Keywords: broad neutralization; cross-protection; in vivo protection; neutralizing antibody; porcine reproductive and respiratory syndrome virus.

Figure 1

Dynamics of development of NAs against the PRRSV isolate used for immunization in Experiment A and Experiment B. Statistically significant differences (p < 0.05) are marked with a * symbol.

Figure 2

GMT of NAs against the immunization and challenge PRRSV isolates in immunized pigs and against challenge PRRSV isolate in control pigs in the eight groups included in the study from the day of challenge to the end of the experiment in Experiment A. The graph illustrates the GMT ± standard deviation.

Figure 3

GMT of NAs against the challenge virus on D70 of the experiment (i.e day of challenge) in groups in which sterilizing immunity was observed, groups in which viremia was not detected but the challenge virus was occasionally detected in tonsils and groups in which viremia was detected upon challenge of immunized pigs in experiment A. Each box represents 25–75% of observation. Whiskers above and below of each box represent the lowest datum still within 1.5 interquartile range (IQR) of the lower quartile, and the highest datum still within 1.5 IQR of the upper quartile. Solid line within each box is the median. Statistically significant differences are highlighted by different letters.

Figure 4

GMT of NAs against the immunization and challenge PRRSV isolates in immunized pigs and against challenge PRRSV isolate in control pigs in the eight groups included in the study from the day of challenge to the end of the experiment in experiment B. The graph illustrates the GMT ± standard deviation.