Oral Administration with Recombinant Attenuated Regulated Delayed Lysis Salmonella Vaccines Protecting against Staphylococcus aureus Kidney Abscess Formation

Abstract

Abscess formation is one of the main symptoms of Staphylococcus aureus infection. It is very important to inhibit abscess formation for preventing S. aureus persistent infection. To find a feasible solution, the live oral vaccines delivering S. aureus antigens, rEsxAB and rHlam, were constructed, which were based on the attenuated regulated delayed lysis Salmonella enterica subspecies Serovar Typhimurium strain χ11802, and the inhibiting effect on abscess formation was evaluated in mice kidneys. As the results showed, after oral administration, humoral immunity was induced via the mucosal route as the antigen-specific IgG in the serum and IgA in the intestinal mucus both showed significant increases. Meanwhile, the production of IFN-γ and IL-17 in the kidney tissue suggested that Th1/Th17-biased cellular immunity played a role in varying degrees. After challenged intravenously (i.v.) with S. aureus USA300, the χ11802(pYA3681−esxAB)-vaccinated group showed obvious inhibition in kidney abscess formation among the vaccinated group, as the kidney abscess incidence rate and the staphylococcal load significantly reduced, and the kidney pathological injury was improved significantly. In conclusion, this study provided experimental data and showed great potential for live oral vaccine development with the attenuated regulated delayed lysis Salmonella Typhimurium strains against S. aureus infection.

Homologous Sequential Immunization Using Salmonella Oral Administration Followed by an Intranasal Boost with Ferritin-Based Nanoparticles Enhanced the Humoral Immune Response against H1N1 Influenza Virus

“…In this study, we used the regulated delayed lysis Salmonella strain χ11802 as a vehicle with which to deliver an in situ nanoparticle vaccine. The lysis strain was designed to include the regulated delayed synthesis of the desired antigen as well as regulated delayed lysis after immunization due to the absence of arabinose in vivo ( 23 ), thereby resulting in increased efficiency in inducing a specific humoral immune response in both chicken ( 24 , 37 ) and mouse ( 26 , 38 ) studies, as found previously. The synthesized 3M2e-ferritin protein could self-assemble into a 24-mer nanocage and then be released into the host environment during Salmonella lysis to yield the desired in situ nanoparticles, as expected.…”