Proline-Rich Region of Pneumococcal Surface Proteins A and C Contains Surface-Accessible Epitopes Common to All Pneumococci and Elicits Antibody-Mediated Protection against Sepsis

• Published in: Infection and Immunity 2010-05, Vol.78 (5), p.2163-2172
• Main Authors: Daniels, Calvin C, Coan, Patricia, King, Janice, Hale, Joanetha, Benton, Kimberly A, Briles, David E, Hollingshead, Susan K
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies, Bacterial - immunology; Antibodies, Monoclonal - administration & dosage; Bacterial Proteins - immunology; Bacteriology; Biological and medical sciences; Conservation; Conserved Sequence - immunology; Cross-protection; Cross-reactivity; Epitopes; Epitopes - immunology; Flow cytometry; Fundamental and applied biological sciences. Psychology; Humans; Immune response; Immunity; Immunization, Passive; Infection; Mice; Mice, Inbred CBA; Microbial Immunity and Vaccines; Microbiology; Miscellaneous; Molecular Sequence Data; Monoclonal antibodies; Pneumococcal Infections - immunology; Pneumococcal Infections - prevention & control; Protein structure; PspA protein; Sepsis; Sepsis - immunology; Sepsis - prevention & control; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; surface protein A; Vaccines; Virulence; Virulence Factors - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01199-09

Pneumococcal surface protein A (PspA) and PspC of Streptococcus pneumoniae are surface virulence proteins that interfere with complement deposition and elicit protective immune responses. The C-terminal halves of PspA and PspC have some structural similarity and contain highly cross-reactive proline-rich (PR) regions. In many PR regions of PspA and PspC, there exists an almost invariant nonproline block (NPB) of about 33 amino acids. Neither the PR regions nor their NPB exhibit the alpha-helical structure characteristic of much of the protection-eliciting N-terminal portions of PspA and PspC. Prior studies of PspA and PspC as immunogens focused primarily on the alpha-helical regions of these molecules that lack the PR and NPB regions. This report shows that immunization with recombinant PR (rPR) molecules and passive immunization with monoclonal antibodies reactive with either NPB or PR epitopes are protective against infection in mice. PR regions of both PspA and PspC were antibody accessible on the pneumococcal surface. Our results indicate that while PspA could serve as a target of these protective antibodies in invasive infections, PspC might not. When antibody responses to rPR immunogens were evaluated by using flow cytometry to measure antibody binding to live pneumococci, it was observed that the mice that survived subsequent challenge produced significantly higher levels of antibodies reactive with exposed PR epitopes than the mice that became moribund. Due to their conservation and cross-reactivity, the PR regions and NPB regions represent potential vaccine targets capable of eliciting cross-protection immunity against pneumococcal infection.