Periodic Reporting for period 3 - PIGSs (Program for Innovative Global Prevention of Streptococcus suis.) Reporting period: 2020-06-01 to 2022-08-31 Summary of the context and overall objectives of the project The problems addressed by PIGSs (Program for Innovative Global prevention of Streptococcus suis) are the major economic losses to the pig production industry worldwide and the animal health burden caused by infections with the bacterium Streptococcus suis. This pathogen can cause invasive disease in pigs with symptoms such as acute sepsis, meningitis, endocarditis, pneumonia and arthritis often being reported. Almost 100% of pig farms worldwide have carrier animals. Whether or not S. suis causes disease in pigs depends on pathogen factors, hosts factors, environmental factors and their interactions. It depends on the genetic constitution of the microbial pathogen as well as on the susceptibility of the host which can be influenced by co-infection, age, immunity, microbiota etc. In addition, environmental factors such as stress and hygiene factors may influence the interaction by altering host or microbiota or ‘behaviour’ (referring to a neutral commensal carriage - or virulent state) of the pathogen. This knowledge will be used to develop innovations for disease prevention through vaccination, promoting colonization resistance to S. suis and stimulating innate immunity in young piglets. Additionally, the knowledge generated will lead to the development of diagnostic markers for disease-causing strains which will for the first time make it possible to study infection dynamics on farms and identify risk factors in farming practices as well as strategies to prevent or control disease outbreaks. A major goal of the PIGSs project is to increase our understanding of the host-pathogen-environment interactions in S. suis infections in pigs, and thereby strengthening the evidence base for new innovations and effective prevention and control strategies. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The main goal of the PIGSs project is to increase our understanding of the host-pathogen-environment interactions in S. suis infections in pigs, and thereby strengthening the evidence base for new innovations and effective prevention and control strategies. This overall goal (above) is further divided into the following specific objectives to be realised within the project’s duration: • Objective 1 is to increase understanding of the pathogenesis of S. suis by characterizing the role of partly or uncharacterized virulence factors in pathogenesis (covered by WP1 and WP2).• Objective 2 is to find microbial solutions to reduce the risk of S. suis invasive disease and support intestinal physiology during weaning through studying the interplay of microbiota with the pig innate immune system and the antagonism of S. suis by specific commensals in vivo (covered by WP3).• Objective 3 is to elucidate how influenza and porcine reproductive and respiratory syndrome virus (PRRSV) coinfection with S. suis contributes to disease and failure of interventions (covered by WP4).• Objective 4 is to determine the main risk factors (besides S. suis strain virulence) involved in the development of clinical disease caused by S. suis and to determine the impact of disease in piglets (covered by WP5).• Objective 5 is to identify and develop (1) novel diagnostic methods for identification of disease-causing strains of S. suis, and (2) preventive strategies that inhibit growth S. suis (covered by WP3 and WP6). • Objective 6 is to promote the sustainable impact of the PIGSs projects’ results and to contribute to a more scientifically literate society through public engagement and communication of the research and innovations of PIGSs beyond its own community (covered by WP8).The project outputs will impact on understanding host-pathogen-environment interactions of S. suis infections through the genome sequencing of a large collection of S. suis isolates from representative geographic areas of the major pork producing countries and performing genome-wide-association studies with invasive disease and asymptomatic carriage. New diagnostic methods have been developed for global monitoring of infection risk and tested on case-farms. Epidemiology studies have determined risk factors for invasive S. suis disease, including the role of co-infections, and for the first time properly assess the dynamics of the disease on a representative farm. We also increased our understanding of the virulence mechanisms involved in pathogenesis including interactions of S. suis with the innate immune system. The project outputs have strengthened the evidence base for prevention and control strategies through testing of novel conserved vaccine antigens in pigs and prevention strategies based on manipulation of the microbiota and stimulation and maturation of the innate immune system.During project period 3, all work packages have continued their work and all work has been completed, despite major delays caused by the Covid-19 pandemic. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Control of S. suis in pig herds is in general hampered by the lack of vaccines that provide protection against multiple serotypes and strains. This is due to the high genotypic, phenotypic and geographic variability that exits among strains, between and within serotypes. One of our ambitions is to develop a global cross-protective protein subunit vaccine through the use of GWAS to select antigen candidates that are conserved in disease-causing isolates. This innovative and novel approach of combining GWAS and reverse vaccinology will only become possible because of our ambition to sequence a large global collection of isolates from all major pork-producing regions of the world. The second ambition is to develop innovations in diagnostics for disease-causing strains of S. suis based on GWAS. This original idea will overcome the inability to distinguish virulent disease-causing strains from non-virulent strains. Addressing this issue will for the first time, allow use of diagnostics to guide antibiotic metaphylaxis and vaccination use to control S. suis outbreaks. This increases efficiency and contributes to the reduction of antibiotic use in pig farming.Longer-term the PIGSs project expects to contribute to substantially reducing S. suis disease in pigs and thereby in animal health and welfare. Related documents Logo PIGSs.png
