Project: Program for Innovative Global Prevention of Streptococcus suis (PIGSs)

Streptococcus (S.) suis is an important swine pathogen that causes major economic losses in the pig farming industry worldwide. S. suis bacteria cause a variety of clinical syndromes which include meningitis, pneumonia, and sudden death. S. suis is considered a zoonotic agent of human meningitis and streptococcal toxic-like syndrome. Increasing incidence and severity of S. suis infections in humans and especially pigs is being reported but there are currently no effective strategies to prevent S. suis disease. Moreover, S. suis infections are one of the most frequent reason to prescribe antibiotics as a metaphylactic measure, contributing to the emergence and spread of antibiotic resistance in pig herds worldwide. Therefore, alternative treatments such as vaccination are of interest.

Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases. A major challenge to the development of an efficacious cross-protective vaccine against S. suis is the high genotypic, phenotypic and geographic variability that exists among strains. To identify conserved genes in diseased-associated isolates across different geographical regions, we perform genome-wide association studies (GWAS) on at least 1000 S. suis genome sequences in a reverse vaccinology (RV) approach to predict potential vaccine antigens broadly conserved among disease-causing strains of different serotypes (Fig. 1). The RV approach involves the use of bioinformatic tools to identify secreted or surface-exposed proteins containing functional domains considered to be important for host-microbe interactions and pathogenesis, as these exposed protein regions have the highest chance of raising an effective immune response and eliciting opsonising antibodies. Candidate antigens will be expressed and purified using the high-throughput platform of the Structural Genomics Consortium in the University of Oxford. The most promising antigens will be tested alone and in combination for protection against a lethal challenge of related strains of S. suis in cesarian-derived and colostrum-deprived piglets. The project outputs will lead to the possibility of combining protective epitopes of different allelic variants into one protein antigen to broaden cross-protection of the vaccine and effectively limit S. suis disease.

Streptococcus (S.) suis is an important swine pathogen that causes major economic losses in the pig farming industry worldwide. S. suis bacteria cause a variety of clinical syndromes which include meningitis, pneumonia, and sudden death. S. suis is considered a zoonotic agent of human meningitis and streptococcal toxic-like syndrome. Increasing incidence and severity of S. suis infections in humans and especially pigs is being reported but there are currently no effective strategies to prevent S. suis disease. Moreover, S. suis infections are one of the most frequent reason to prescribe antibiotics as a metaphylactic measure, contributing to the emergence and spread of antibiotic resistance in pig herds worldwide. Therefore, alternative treatments such as vaccination are of interest.

Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases. A major challenge to the development of an efficacious cross-protective vaccine against S. suis is the high genotypic, phenotypic and geographic variability that exists among strains. To identify conserved genes in diseased-associated isolates across different geographical regions, we perform genome-wide association studies (GWAS) on at least 1000 S. suis genome sequences in a reverse vaccinology (RV) approach to predict potential vaccine antigens broadly conserved among disease-causing strains of different serotypes (Fig. 1). The RV approach involves the use of bioinformatic tools to identify secreted or surface-exposed proteins containing functional domains considered to be important for host-microbe interactions and pathogenesis, as these exposed protein regions have the highest chance of raising an effective immune response and eliciting opsonising antibodies. Candidate antigens will be expressed and purified using the high-throughput platform of the Structural Genomics Consortium in the University of Oxford. The most promising antigens will be tested alone and in combination for protection against a lethal challenge of related strains of S. suis in cesarian-derived and colostrum-deprived piglets. The project outputs will lead to the possibility of combining protective epitopes of different allelic variants into one protein antigen to broaden cross-protection of the vaccine and effectively limit S. suis disease.