Pneumococcal disease is a serious public health problem worldwide and an important cause of morbidity and mortality among children and adults in developing countries. Although vaccination is among the most effective approaches to prevent and control pneumococcal diseases, approved vaccines have limited protective effects. We developed a pneumococcal protein-polysaccharide conjugate vaccine that is mediated by the noncovalent interaction between biotin and streptavidin. Biotinylated type IV capsular polysaccharide was incubated with a fusion protein containing core streptavidin and Streptococcus pneumoniae virulence protein and relied on the noncovalent interaction between biotin and streptavidin to prepare the protein-polysaccharide conjugate vaccine. Analysis of vaccine efficacy revealed that mice immunized with the protein-polysaccharide conjugate vaccine produced antibodies with high potency against virulence proteins and polysaccharide antigens and were able to induce Th1 and Th17 responses. The antibodies identified using an opsonophagocytic assay were capable of activating the complement system and promoting pathogen elimination by phagocytes. Additionally, mice immunized with the protein-polysaccharide conjugate vaccine and then infected with a lethal dose of Streptococcus pneumoniae demonstrated induced protective immunity. The data indicated that the pneumococcal protein-polysaccharide (biotin-streptavidin) conjugate vaccine demonstrated broad-spectrum activity applicable to a wide range of people and ease of direct coupling between protein and polysaccharide. These findings provide further evidence for the application of biotin-streptavidin in S. pneumoniae vaccines.
Keywords: Streptococcus pneumoniae; biotin; pneumococcal surface adhesin A; pneumococcal surface protein A; protein-polysaccharide conjugate vaccine; streptavidin.