AsopBDeletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live AttenuatedSalmonella entericaVaccines

Abstract

SopB is a virulence factor of Salmonella encoded by SPI-5. Salmonella sopB deletion mutants are impaired in their ability to cause local inflammatory responses and fluid secretion into the intestinal lumen and also can enhance the immunogenicity of a vectored antigen. In this study, we evaluated the effects on immunogenicity and the efficacy of a sopB deletion mutation on two Salmonella enterica serovar Typhimurium vaccine strains with different attenuating mutations expressing a highly antigenic ␣-helical region of the Streptococcus pneumoniae surface protein PspA from an Asd ؉ -balanced lethal plasmid. After oral administration to mice, the two pairs of strains induced high levels of serum antibodies specific for PspA as well as to Salmonella antigens. The levels of antigen-specific serum immunoglobulin G (IgG) and mucosal IgA were higher in mice immunized with sopB mutants. Enzyme-linked immunospot assay results indicated that the spleen cells from mice immunized with a sopB mutant showed higher interleukin-4 and gamma interferon secretion levels than did the mice immunized with the isogenic sopB ؉ strain. The sopB mutants also induced higher numbers of CD4 ؉ CD44 hi CD62L hi and CD8 ؉ CD44 hi CD62L hi central memory T cells. Eight weeks after primary oral immunization, mice were challenged with 100 50% lethal doses of virulent S. pneumoniae WU2. Immunization with either of the sopB mutant strains led to increased levels of protection compared to that with the isogenic sopB ؉ parent. Together, these results demonstrate that the deletion of sopB leads to an overall enhancement of the immunogenicity and efficacy of recombinant attenuated Salmonella vaccine strains.

Immune Responses to Recombinant Pneumococcal PsaA Antigen Delivered by a Live Attenuated Salmonella Vaccine

“…These constructs failed to induce protective immunity, which is similar to the findings of Ogunniyi et al (58) and Gor et al (30). Compared to previously reported results using PspA as the antigen (42,76), our intraperitoneal challenge results are disappointing, even when we immunized and boosted mice intranasally with a strain synthesizing full-length PsaA (see Table S1 in the supplemental material). One reason for these results may be the masking of PsaA by the cell capsule.…”

“…S1 in the supplemental material). Although the titer is comparable to or higher than titers reported by others, it is lower than anti-PspA titers when PspA is delivered by Salmonella vectors, which are generally 2 12 to 2 15 (42,76). Thus, there may not be enough antibodies to block the binding of S. pneumoniae to the nasopharyngeal cell surface.…”

“…The antibody titer against PsaA may be increased further by including the sopB mutation in our Salmonella vector strain. Introduction of a ⌬sopB mutation into attenuated Salmonella has been shown to enhance the immune response against vectored antigens (42,46).…”

LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

“…Induction of IgA responses provides specific protection against many respiratory, enteric, and genital infections (91). As we know, recombinant attenuated Salmonella vaccines (RASVs) have been used mostly to induce mucosal and systemic immunity either to Salmonella itself or to heterologous antigens delivered by RASVs (95)(96)(97). Live attenuated Y. pseudotuberculosis strains as oral vaccines against different pathogens, including those causing plague, have been explored (36)(37)(38)(39)(40).…”

Effect of Deletion of Genes Involved in Lipopolysaccharide Core and O-Antigen Synthesis on Virulence and Immunogenicity of Salmonella enterica Serovar Typhimurium

“…Outer membrane proteins were prepared as described previously (32). An enzyme-linked immunosorbent assay (ELISA) was used to assay serum antibodies against S. Typhimurium LPS, rPspA, and bacterial outer membrane proteins, including those from Salmonella (SOMPs), as previously described (38). Color development (absorbance) was recorded at 405 nm using a SpectraMax M2e automated ELISA plate reader (Molecular Devices, Menlo Park, CA).…”