title: Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae.
abstract: A promising alternative vaccine candidate to reduce the burden of pneumococcal diseases is the protein antigen PspA (Pneumococcal surface protein A). Since concomitant colonization with two or more pneumococcal strains is very common in children, we aimed to determine if immunization with PspA would be able to control co-colonization. We evaluated nasal immunization with recombinant PspA (rPspA) in a model of co-colonization with two strains expressing different PspAs. Mice were immunized intranasally with rPspAs from clades 1 to 4 (rPspA1, rPspA2, rPspA3 or rPspA4) using whole-cell pertussis vaccine (wP) as adjuvant. Mice were then challenged with a mixture of two serotype 6B isolates St491/00 (PspA1) and St472/96 (PspA4). Immunization with rPspA1+wP and rPspA4+wP reduced colonization with both strains and the mixture of rPspA1+rPspA4+wP induced greater reduction than a single antigen. Immunization rPspA1+rPspA4+wP also reduced colonization when challenge experiments were performed with a mixture of isolates of serotypes 6B (PspA3) and 23F (PspA2). Furthermore, none of the tested formulations led to a pronounced increase in colonization of one isolate over the other, showing that the vaccine strategy would not favor replacement. Interestingly, the adjuvant wP by itself already led to some reduction in pneumococcal colonization, indicating the induction of non-specific immune responses. Anti-rPspA IgG was observed in serum, nasal wash (NW) and bronchoalveolar lavage fluid (BALF) samples, whereas animals inoculated with formulations containing the adjuvant wP (with or without rPspA) showed higher levels of IL-6 and KC in NW and increase in tissue macrophages, B cells and CD4+T cells in BALF.
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Rafaella O
authors.initials: RO
authors.lastname: Tostes
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Tasson C
authors.initials: TC
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Josefa B
authors.initials: JB
authors.lastname: da Silva
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Schanoski
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Maria Leonor S
authors.initials: ML
authors.lastname: Oliveira
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Eliane N
authors.identifier: http://orcid.org/0000-0003-1689-5366
authors.initials: EN
authors.lastname: Miyaji
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D010567:Pertussis Vaccine; D022242:Pneumococcal Vaccines; D014614:Vaccines, Synthetic; C051592:pneumococcal surface protein A