title: Immune responses to recombinant pneumococcal PsaA antigen delivered by a live attenuated Salmonella vaccine.
abstract: Streptococcus pneumoniae is a leading cause of morbidity and mortality among children worldwide and particularly in developing countries. In this study, we evaluated PsaA, a conserved antigen important for S. pneumoniae adhesion to and invasion into nasopharynx epithelia, for its ability to induce protective immunity against S. pneumoniae challenge when delivered by recombinant attenuated Salmonella vaccine (RASVs) strains. RASVs were engineered to synthesize PsaA peptides of various lengths. Vaccination with an RASV synthesizing full-length PsaA induced high titers of anti-PsaA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes, nasal washes, and lung homogenates) sites. BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains. None of the vaccine constructs provided protection against intraperitoneal challenge with S. pneumoniae strain WU2 (serotype 3). Immunization with RASVs synthesizing truncated PsaA generated lower titers of IgA and IgG and did not provide significant protection. Our results showed that RASVs synthesizing full-length PsaA can provide protection against nasal colonization by some S. pneumoniae strains. PsaA may be a useful addition to a multivalent vaccine, providing protection against pneumonia, otitis media, and other diseases caused by S. pneumoniae.
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401, USA.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Huoying
authors.initials: H
authors.lastname: Shi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scarpellini
authors.forename: Ascencion
authors.initials: A
authors.lastname: Torres-Escobar
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Roland
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D022562:Salmonella Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; C085000:PsaA protein, Streptococcus; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic