H2020 PIGS Project: Innovative Global Prevention Program for Streptococcus suis.

Nearly every pig farm in the world has pathogenic strains of Streptococcus suis, which can also infect humans. Much-needed surveillance and prevention tools are being developed. Streptococcus suis (S. suis) is a bacterial pathogen that causes conditions such as acute sepsis, meningitis, endocarditis, and pneumonia in young pigs. It is also frequently associated with porcine respiratory syndrome coronavirus 2 (PRNS), a leading cause of swine mortality. Furthermore, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, S. suis is zoonotic, one of many pathogens that can be transmitted from animals to humans. The EU-funded PIGSs project is improving our understanding of S. suis pathogenicity, enabling the development of essential vaccines and surveillance tools. Streptococcus suis and the Antibiotic Conundrum Outbreaks of pathogenic S. suis infection are very common. Pig studies showed that, in affected European farms, between 3.3% and 4% of animals had invasive S. suis disease. This costs the industry millions, not to mention the economic costs of human illness. A recent study in Southeast Asia, where cases are highest, reported that the economic costs of human illness amount to millions of euros annually due to direct and indirect medical care costs and lost productivity. To date, there is no cross-protection vaccine licensed in Europe. According to Jerry Wells, project coordinator at Wageningen University & Research in the Netherlands, "The lack of effective surveillance methods and vaccines has led to inadequate prevention and a global reliance on widespread antibiotic use."

This leads to increased antibiotic resistance, which can spread to other pathogens that infect animals and humans, and to an increase in the presence of antibiotics in food for human consumption." Harnessing polymerase chain reaction and bioinformatics tools Unraveling the mechanisms of S. suis disease is challenging. Only a subset of strains are associated with illnesses that result in severe morbidity and mortality. "Using a global collection of around 2,000 non-pathogenic and pathogenic strains, PIGS identified genes that are highly conserved in pathogenic strains but absent in the rest.

These markers were used to develop quantitative polymerase chain reaction (PCR) assays that rapidly amplify small DNA fragments into millions of copies. PCR assays can be used for surveillance of pathogenic isolates on farms,” explains Wells. This will also enable targeted prevention and treatment strategies, for example, for sows that transmit pathogenic strains to their offspring. Finally, the team used bioinformatics tools to detect conserved antigens (protein sequences conserved across all pathogenic S. suis strains) and elicit protective antibody responses in pigs. The team is currently evaluating how best to enhance this response and developing assays to assess protection induced by these vaccines in future trials.

Mechanisms, Risk Factors, and Vaccines The PIGS project may be coming to an end, but much more information is expected to be gained from ongoing experiments and analyses. The team is currently elucidating the mechanisms by which the pathogen strains survive or are transmitted. Furthermore, Wells notes that “a large epidemiological study is still underway, from which we hope to gain further insight into the factors on different farms that increase the risk of S. suis disease. Our ongoing vaccine trial in piglets could be revolutionary, revealing new vaccination strategies for young piglets.” PIGS has significantly improved our understanding of the interactions between the host, pathogen, and environment of S. suis. This will support the development of more effective vaccines and control strategies, as well as large-scale on-farm surveillance, to reduce or eliminate the disease.