Brucella abortus ΔrpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis. Issue 42 (30th September 2016)

• Record Type: Journal Article
• Authors: Willett, Jonathan W.; Herrou, Julien; Czyż, Daniel M.; Cheng, Jason X.; Crosson, Sean
• Is Part Of: Vaccine. Volume 34:Issue 42(2016)
• Page Start: 5073
• Page End: 5081
• Publication Date: 2016-09-30
• Subjects: Antibody -- ecfG -- phyR -- Brucellosis -- General stress response -- rpoE1 -- Vaccine; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.08.076
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: The Brucella abortus general stress response (GSR) system regulates activity of the alternative sigma factor, σ E1, which controls transcription of approximately 100 genes and is required for persistence in a BALB/c mouse chronic infection model. We evaluated the host response to infection by a B. abortus strain lacking σ E1 (Δ rpoE1 ), and identified pathological and immunological features that distinguish Δ rpoE1 -infected mice from wild-type (WT), and that correspond with clearance of Δ rpoE1 from the host. Δ rpoE1 infection was indistinguishable from WT in terms of splenic bacterial burden, inflammation and histopathology up to 6 weeks post-infection. However, Brucella -specific serum IgG levels in Δ rpoE1 -infected mice were 5 times higher than WT by 4 weeks post-infection, and remained significantly higher throughout the course of a 12-week infection. Total IgG and Brucella -specific IgG levels peaked strongly in Δ rpoE1 -infected mice at 6 weeks, which correlated with reduced splenomegaly and bacterial burden relative to WT-infected mice. Given the difference in immune response to infection with wild-type and Δ rpoE1, we tested whether Δ rpoE1 confers protective immunity to wild-type challenge. Mice immunized with Δ rpoE1 completely resisted WT infection and had significantly higher serum titers of Brucella -specific IgG, IgG2a and IFN-γ after WT challenge relative to age-matched naïve mice. We conclude that immunization of BALB/c mice with the B. abortus GSR pathway mutant, Δ rpoE1, elicits an adaptive immune response that confers significant protective immunity against WT infection.