Non-technical Summary: Currently, there are no efficacious vaccines to protect piglets against disease caused by the emerging zoonotic (transmissible from animals to humans) pathogen, Streptococcus suis. Porcine S. suis disease is a major cause of morbidity and mortality in weaned piglets and is a significant economic burden on pork producers globally. Losses to the pig industry globally are in the range of tens of millions to several hundred millions USD annually worldwide. Human S. suis disease can be serious and sometimes fatal, which places a heavy societal burden on public health. Infected pigs are the principal source of human infection; hence, an efficacious vaccine to thwart pig S. suis disease will not only increase revenues of pork producers but also significantly reduce the incidence of human infection, and thereby positively impact public health worldwide. A major impediment to development of highly efficacious vaccines to pig S. suis disease (porcine Streptococcosis) is the fact that different variants of this pathogen (i.e., many serotypes and multiple strains within each serotype) cause disease in different geographical regions of the globe. This means that a vaccine that provides exemplary protection against one variant prevalent in a particular region of the world may not necessarily protect against a variant that causes disease in another part of the world. Therefore, for a vaccine, to be effective, must be able to block infection caused by all / majority of the globally clinically relevant S. suis serotypes and strains (universal or broadly protective vaccines). Consequently, from the point of view of vaccine development, it is imperative that the vaccine be made up of components that are "shared" or "conserved" by the vast majority of S. suis capable of causing disease. An important first step toward such universal / broadly protective vaccines is to identify pathogen components (such as proteins) that are highly conserved across all / majority of S. suis with disease causing potential; however, this is easier said than done and presents a stiff challenge. This is because highly conserved proteins serve indispensable functions to the pathogen and consequently, are "hidden" by the pathogen by highly evolved "decoy" mechanisms that prevents the host from recognizing these conserved proteins during natural infection. Novel and innovative techniques are therefore required to identify such proteins. The proprietary protein antigen discovery tool (called Proteomics-based Expression Library Screening or PELS) proposed in this project is one such platform for identification of proteins conserved across diverse S. suis. The technology employs highly specific probes, including antibodies, to identify pathogen proteins. Here, PELS will be innovatively applied to interrogate the entire repertoire of proteins (the proteome) produced by individual S. suis variants comprising a group of 15 serotypes / strains, representative of those causing disease globally. Proteins that react with the antibodies are separated from the rest of the proteome of that particular variant and then identified using tandem mass spectrometry. Sophisticated computer-based algorithms (bioinformatics) will then be employed to compare the proteins identified from each variant to arrive at a panel of highly conserved proteins. A subset of these proteins will be further prioritized on the basis of characteristics that render them suitable as vaccine components. Finally, the prioritized proteins will be produced in a purified form and formulated as a vaccine. In this phase I SBIR project, efficacy of such a vaccine will be determined by the ability of the vaccine to protect weaned piglets from experimental disease caused by a S. suis variant with disease causing potential that is not part of the 15 serotypes / strains examined in this study. Further studies, such as those in phase II, will evaluate the ability of the vaccine to protect piglets against d
