The present invention is based, in part, on flagellin adjuvant used to enhance immune responses directed against Streptococcus pneumoniae, in particular, to enhance immune responses to polypeptide antigens (e.g., PspA) and capsular polysaccharide from S. pneumoniae. In representative embodiments, the invention provides a fusion protein comprising a flagellin adjuvant and one more polypeptide antigens from S. pneumoniae. In other embodiments, the invention provides a conjugate comprising a flagellin adjuvant covalently linked to a capsular polysaccharide from one or more serotypes of S. pneumoniae. Also provided are compositions comprising the fusion proteins and/or conjugates of the invention as well as immunogenic formulations comprising the inventive fusion proteins, conjugates and/or compositions. The invention also provides methods of producing an immune response against S. pneumoniae and methods of protecting a subject from S. pneumoniae infection by administering the fusion proteins, conjugates, compositions and/or immunogenic formulations of the invention to the subject.
