Brucella abortus ΔrpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis.

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) (ΔrpoE1), and identified pathological and immunological features that distinguish ΔrpoE1-infected mice from wild-type (WT), and that correspond with clearance of ΔrpoE1 from the host. ΔrpoE1 infection was indistinguishable from WT in terms of splenic bacterial burden, inflammation and histopathology up to 6weeks post-infection. However, Brucella-specific serum IgG levels in ΔrpoE1-infected mice were 5 times higher than WT by 4weeks post-infection, and remained significantly higher throughout the course of a 12-week infection. Total IgG and Brucella-specific IgG levels peaked strongly in ΔrpoE1-infected mice at 6weeks, 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 ΔrpoE1, we tested whether ΔrpoE1 confers protective immunity to wild-type challenge. Mice immunized with ΔrpoE1 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, ΔrpoE1, elicits an adaptive immune response that confers significant protective immunity against WT infection.

• Authors: Jonathan W Willett, Julien Herrou, Daniel M Czyz, Jason X Cheng, Sean Crosson
• Journal: Vaccine (Vaccine) Vol. 34 Issue 42 Pg. 5073-5081 (09 30 2016) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 27591954 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Brucella Vaccine
• Immunoglobulin G
• Sigma Factor
• Interferon-gamma

Topics

• Adaptive Immunity
• Animals
• Brucella Vaccine (administration & dosage, genetics, immunology)
• Brucella abortus (genetics, immunology)
• Brucellosis (immunology, prevention & control)
• Disease Models, Animal
• Immunoglobulin G (blood)
• Interferon-gamma (biosynthesis)
• Mice
• Mice, Inbred BALB C
• Mutation
• Sigma Factor (deficiency, genetics)
• Spleen (microbiology, pathology)