The success of
polysaccharide conjugate vaccines represents a major advance in the prevention of
pneumococcal disease, but the power of these
vaccines is limited by partial spectrum of coverage and high cost.
Vaccines using immunoprotective
proteins are a promising alternative type of
pneumococcal vaccines. In this study, we constructed a library of
antisera against conserved pneumococcal
proteins predicted to be associated with cell surface or virulence using a combination of bioinformatic prediction and immunization of rabbits with
recombinant proteins. Screening of the library by an opsonophagocytosis killing (OPK) assay identified the OPK-positive
antisera, which represented 15 (OPK-positive)
proteins. Further tests showed that virtually all of these OPK-positive
antisera conferred passive protection against lethal
infection of virulent pneumococci. More importantly, immunization with recombinant forms of three OPK-positive
proteins (SP148, PBP2b, and
ScpB), alone or in combination, conferred significant protection against lethal challenge of pneumococcal strains representing capsular serotypes 3, 4, and 6A in a mouse
sepsis model. To our best knowledge, this work represents the first example in which novel
vaccine candidates are successfully identified by the OPK screening. Our data have also provided further confirmation that the OPK activity may serve as a reliable in vitro surrogate for evaluating
vaccine efficacy of pneumococcal
proteins.