Broadly protective glycoconjugate vaccines targeting major animal and zoonotic Gram-positive pathogens – CANVAS

This project aims for proof-of-concept that conserved cell wall polysaccharides can be used as targets for broadly protective glycoconjugate vaccines against the bacterial species Streptococcus suis and Staphylococcus aureus, important zoonotic pathogens in pigs and cattle, respectively. This collaboration brings together experts from the Faculty of Veterinary Medicine of Utrecht University, Amsterdam University Medical Center and MSD Animal Health.Gram-positive bacteria have a large impact on human and animal health. Especially the genera Streptococcus and Staphylococcus comprise a large number of bacteria that cause disease in humans and animals. Many Gram-positive bacteria display capsular polysaccharide serotype variation that supports pathogen escape from the immune system. The use of capsular polysaccharides in traditional capsule-glycoconjugate vaccines often suffer from lack of complete serotype coverage, leading to a shift in serotypes that cause disease. Overall, there is a lack of (broadly protective) vaccines, while antibiotic treatment is either discouraged or less effective due to antimicrobial resistance. Cell wall polysaccharide-antigens often show limited variation across serotypes. Their application as vaccine antigens would therefore overcome the hurdle of narrow serotype specificity of traditional glycoconjugate vaccines, potentially opening up new vaccine options for a wide range of disease-causing bacteria. Successful execution of this project will help reduce animal infections, support healthy farming and indirectly reduce zoonotic and emerging infections in humans.The major cell wall polysaccharide of S. suis and bovine-associated S. aureus were characterized. Although the polysaccharide of S. suis was variable between strains, a conserved motif was identified. Immunization of pigs with the conserved motif induced antibodies that broadly recognized whole S. suis. This discovery highlights the potential for developing broad-spectrum vaccines targeting these pathogens and provides proof-of-concept for leveraging conserved glycan motifs to design vaccines against diverse bacterial pathogens