title: Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice.
abstract: Streptococcus pneumoniae is a major respiratory pathogen that causes high levels of mortality and morbidity in infants and the elderly. Despite the use of antibiotics and vaccines, fatal pneumococcal disease remains prevalent. Pneumococcal surface protein A (PspA), a highly immunogenic surface protein produced by all strains of S. pneumoniae, can elicit protective immunity against fatal pneumococcal infection. We have previously demonstrated that the Vibrio vulnificus FlaB, a bacterial flagellin protein and agonist of TLR5, has strong mucosal adjuvant activity and induces protective immunity upon co-administration with tetanus toxoid. In this study, we have tested whether intranasal immunization with recombinant fusion proteins consisted of PspA and FlaB (PspA-FlaB and FlaB-PspA) is able to elicit more efficient protective mucosal immune responses against pneumococcal infection than immunization with PspA alone or with a stoichiometric mixture of PspA and FlaB. When mice were intranasally immunized with fusion proteins, significantly higher levels of anti-PspA IgG and IgA were induced in serum and mucosal secretions. The mice immunized intranasally with the FlaB-PspA fusion protein were the most protected from a lethal challenge with live S. pneumoniae, as compared to the mice immunized with PspA only, a mixture of PspA and FlaB, or the PspA-FlaB fusion protein. FlaB-PspA also induced a cross protection against heterologous capsular types. These results suggest that a FlaB-PspA fusion protein alone could be used as an anti-pneumococcal mucosal vaccine or as an effective partner protein for multivalent capsular polysaccharide conjugate vaccines.
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-gun, Jeonnam 519-809, South Korea.
authors.forename: Chung Truong
authors.initials: CT
authors.lastname: Nguyen
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Myoung Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D005260:Female; D005408:Flagellin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D041261:Vibrio vulnificus / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; C051592:pneumococcal surface protein A; D005408:Flagellin; C416532:flaB flagellin