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

The control of porcine reproductive and respiratory syndrome (PRRS) remains a significant challenge due to the genetic and antigenic variability of the causative virus (PRRSV). Predominantly, PRRSV management includes using vaccines and live virus inoculations to confer immunity against PRRSV on farms. While understanding cross-protection among strains is crucial for the continued success of these interventions, understanding how genetic diversity translates to antigenic diversity remains elusive. We developed machine learning algorithms to estimate antigenic distance in silico, based on genetic sequence data, and identify differences in specific amino acid sites associated with antigenic differences between viruses. First, we obtained antigenic distance estimates derived from serum neutralization assays cross-reacting PRRSV monospecific antisera with virus isolates from 27 PRRSV1 viruses circulating in Europe. Antigenic distances were weakly to moderately associated with ectodomain amino acid distance for open reading frames (ORFs) 2 to 4 (ρ < 0.2) and ORF5 (ρ = 0.3), respectively. Dividing the antigenic distance values at the median, we then categorized the sera-virus pairs into two levels: low and high antigenic distance (dissimilarity). In the machine learning models, we used amino acid distances in the ectodomains of ORFs 2 to 5 and site-wise amino acid differences between the viruses as potential predictors of antigenic dissimilarity. Using mixed-effect gradient boosting models, we estimated the antigenic distance (high versus low) between serum-virus pairs with an accuracy of 81% (95% confidence interval, 76 to 85%); sensitivity and specificity were 86% and 75%, respectively. We demonstrate that using sequence data we can estimate antigenic distance and potential cross-protection between PRRSV1 strains. IMPORTANCE Understanding cross-protection between cocirculating PRRSV1 strains is crucial to reducing losses associated with PRRS outbreaks on farms. While experimental studies to determine cross-protection are instrumental, these in vivo studies are not always practical or timely for the many cocirculating and emerging PRRSV strains. In this study, we demonstrate the ability to rapidly estimate potential immunologic cross-reaction between different PRRSV1 strains in silico using sequence data routinely collected by production systems. These models can provide fast turn-around information crucial for improving PRRS management decisions such as selecting vaccines/live virus inoculation to be used on farms and assessing the risk of outbreaks by emerging strains on farms previously exposed to certain PRRSV strains and vaccine development among others.

Hazard potential of widespread but hidden historic offshore heavy metal (Pb, Zn) contamination (Gulf of Cadiz, Spain).

Natural and human-induced seabed sediment disturbances affect wide areas of the global coastal ocean. These recurrent to chronic disturbances mobilize significant amounts of material, including substances that have the potential to significantly harm the environment once re-released. This very challenging issue is difficult to deal with if sub-surface contaminant concentrations are unknown. Based on the analysis of 11 new, up to 5-m long sediment cores taken offshore in the Gulf of Cadiz, the contamination history (using the trace elements lead and zinc) is well documented over major parts of the gulf. Ore mining and metal processing industries on the southwestern Iberian Peninsula started five thousand years ago and experienced a first peak during the Roman Period, which can be detected over the entire gulf. The Industrial Era added a massive, shelf-wide heavy metal excursion of unprecedented dimension. This metal contamination to the coastal ocean decreased in the 1990s and appears to be today limited to larger areas off the Tinto/Odiel and Guadiana River mouths. The unforeseen, significant finding of this study is that the gulf-wide, peak heavy metal concentration, stemming from the Industrial Era, is widely overlain by a modern sediment veneer just thick enough to cover the contaminant horizon, but thin enough to have this layer within the reach of natural or human-induced sediment mobilization events.

Similarity of European porcine reproductive and respiratory syndrome virus strains to vaccine strain is not necessarily predictive of the degree of protective immunity conferred.

The objective of this study was to determine the degree of protection conferred by a Lelystad-like modified live virus (MLV) vaccine against a heterologous wild-type porcine reproductive and respiratory syndrome virus (PRRSV) isolate of the same cluster. For this purpose, fourteen 3-week-old piglets were divided into three groups: Group A pigs were vaccinated with a modified live virus vaccine, Group B pigs were used as positive controls, and Group C pigs as negative controls. Twenty-eight days after the last dose of vaccine, all pigs in Groups A and B were inoculated with the Spanish PRRSV strain 5710. To evaluate efficacy, clinical signs were recorded and the presence of challenge virus was determined by virus isolation in blood samples and nasal swabs collected at various time points post-challenge (p.c.) and in tissue samples collected at necropsy 24 days p.c. After challenge, moderate clinical signs were observed in pigs from Groups A and B. In addition, all vaccinated pigs were viremic at least once, although viremia tended to be more sporadic in this group than in Group B pigs. PRRSV was detected in at least one tissue sample from four out of five pigs from Group A and in all pigs from Group B. The results indicate that the protection conferred by the MLV vaccine used in this study against a closely related virulent strain was only partial. The findings suggest that the degree of genetic homology of ORF5 between MLV vaccine and challenge isolate is not a good predictor of vaccine efficacy.

Effects of two commercial European modified-live vaccines against porcine reproductive and respiratory syndrome viruses in pregnant gilts.

The purpose of this study was to assess the effects of two currently available commercial European-type modified-live virus (MLV) vaccines against porcine reproductive and respiratory syndrome in a reproductive pig model. Sixteen 90-day pregnant gilts were divided into four groups and allocated to one of the following intranasal treatments: group A gilts served as negative controls; group B gilts were exposed to a virulent European field strain; group C gilts were exposed to vaccine strain VP046 Bis and group D gilts to vaccine strain All-183. The results indicated that MLV strains can replicate in breeding animals and have the ability to cross the placenta. In particular, viraemia was detected in all gilts in group C and 2/4 gilts in group D, at least at one time point. In addition, transplacental infection was demonstrated in 3/4 gilts in group C and 2/4 gilts in group D. However, congenital and early postnatal infection did not have a marked detrimental effect on piglet performance when compared to negative controls, and no statistically significant differences were observed in most cases. Conversely, the reproductive performance of gilts in group B was significantly worse than that of the other groups. Specifically, the number of born-alive piglets, the survival rate of piglets during lactation and the mean weight of weaned pigs were significantly lower. It was concluded that the two commercial European-type MLV vaccines tested had no marked detrimental effects in pregnant gilts, although the MLV strains can cross the placenta leading to the birth of congenitally infected piglets.