Streptococcus pneumoniae (Spn) is a bacterial pathogen known to colonize the upper respiratory tract and cause serious opportunistic diseases such as
pneumonia,
bacteremia,
sepsis and
meningitis. As a consequence, millions of attributable deaths occur annually, especially among infants, the elderly and immunocompromised individuals. Although current
vaccines, composed of purified pneumococcal
polysaccharide in free form or conjugated to a
protein carrier, are widely used and have been demonstrated to be effective in target groups, Spn has continued to colonize and cause life-threatening disease in susceptible populations. This lack of broad protection highlights the necessity of improving upon the current "gold standard"
pneumococcal vaccines to increase protection both by decreasing colonization and reducing the incidence of sterile-site
infections. Over the past century, most of the pneumococcal
proteins that play an essential role in colonization and pathogenesis have been identified and characterized. Some of these
proteins have the potential to serve as
antigens in a multi-valent
protein vaccine that confers
capsule independent protection. This review seeks to summarize the benefits and limitations of the currently employed
vaccine strategies, describes how leading candidate
proteins contribute to
pneumococcal disease development, and discusses the potential of these
proteins as protective
antigens-including as a hybrid construct.