title: Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice.
abstract: An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1-4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice.
authors.affiliation: Laboratory for Clinical Research on Infectious Disease, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Japan; Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Japan.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Laboratory for Clinical Research on Infectious Disease, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.affiliation: Laboratory for Clinical Research on Infectious Disease, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.affiliation: National Institute of Biomedical Innovation, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Department of Infectious Diseases, Keio University School of Medicine, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ubukata
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.affiliation: Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tomono
authors.affiliation: Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Japan. Electronic address: oishik@nih.go.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D007106:Immune Sera; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; C051592:pneumococcal surface protein A
keywords: Binding of PspA-specific IgG; Cross-protection; PspA fusion protein; PspA vaccine; Streptococcus pneumoniae