title: Immunogenicity of a live recombinant Salmonella enterica serovar typhimurium vaccine expressing pspA in neonates and infant mice born from naive and immunized mothers.
abstract: We are developing a Salmonella vectored vaccine to prevent infant pneumonia and other diseases caused by Streptococcus pneumoniae. One prerequisite for achieving this goal is to construct and evaluate new recombinant attenuated Salmonella vaccine (RASV) strains suitable for use in neonates and infants. Salmonella enterica serovar Typhimurium strain chi9558(pYA4088) specifies delivery of the pneumococcal protective antigen PspA and can protect adult mice from challenge with S. pneumoniae. This strain is completely safe for oral delivery to day-old and infant mice. Here we assess the colonizing ability, immunogenicity, and protective efficacy of chi9558(pYA4088) in neonatal mice. Colonization was assessed in mice 0, 2, 4, or 7 days of age after oral inoculation. In the presence of maternal antibodies, the colonization of lymphoid tissues was delayed, but the immune responses were enhanced in mice born to immunized mothers. Both oral and intranasal routes were used to assess immunogenicity. All orally or intranasally immunized neonatal and infant mice born to either immunized or naïve mothers developed PspA-specific mucosal and systemic immune responses. Mice born to immunized mothers produced higher titers of PspA-specific antibodies in the blood and mucosa and greater numbers of PspA-specific interleukin-4 (IL-4)-secreting cells than mice born to naïve mothers. More importantly, mice born to immune mothers showed a significant increase in protection against S. pneumoniae challenge. These results suggest that strain chi9558(pYA4088) can circumvent some of the limitations of the immature immune system in neonatal and infant mice, generating enhanced protective immune responses in the presence of maternal antibodies.
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Huoying
authors.initials: H
authors.lastname: Shi
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Roland
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: Gunn
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D012480:Salmonella Infections / Q000517:prevention & control; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium; D014614:Vaccines, Synthetic
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D022562:Salmonella Vaccines; D014614:Vaccines, Synthetic; C069816:phage shock protein, Bacteria