Cellular and mucosal immune responses following vaccination with inactivated mutant of Escherichia coli O157:H7

Authors: SCHAUT, ROBERT - Orise Fellow; Boggiatto, Paola; Loving, Crystal; Sharma, Vijay

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2019
Publication Date: 4/22/2019
Citation: Schaut, R.G., Boggiatto, P.M., Loving, C.L., Sharma, V.K. 2019. Cellular and mucosal immune responses following vaccination with inactivated mutant of Escherichia coli O157:H7. Scientific Reports. 9:6401. https://doi.org/10.1038/s41598-019-42861-z.
DOI: https://doi.org/10.1038/s41598-019-42861-z

Interpretive Summary: Shiga-toxin producing E. coli O157:H7 (O157) bacteria can cause severe disease, such as bloody diarrhea, kidney failure, and even death in humans. Cattle are a major source of O157 transmission to humans as these bacteria frequently colonize intestines of these animals, and bacteria shed in feces can contaminate meat and milk produced from these animals. Therefore, reducing fecal shedding of O157 bacteria in cattle through vaccination is a practical approach for limiting the risk of O157 contamination of foods. Increased food safety through vaccination would reduce the risk of O157 transmission to humans, thus lowering the incidence of human illnesses. Here, it is demonstrated that vaccination of cattle with a specific vaccine formulation (inactivated O157 mutant bacteria and an immune stimulant) generated a multicomponent immune response capable of directly or indirectly interacting with specific factors produced by O157 bacterial cells to colonize cattle intestines. One of the immune response components or factors that was detected only in the feces of vaccinated cattle might be directly blocking O157 colonization of cattle intestines. Other components resulting from vaccination included specific types of immune cells and factors produced by these cells that might also be interfering or blocking colonization of cattle intestine by O157. These results provide a platform for developing improved vaccines for controlling O157 persistence and fecal shedding in cattle; outcomes essential for preventing transmission of these bacteria to humans.

Technical Abstract: Shiga toxin-producing Escherichia coli O157:H7 (O157) can cause mild to severe gastrointestinal disease in humans. Although O157 was first linked to human disease in 1982, disease outbreaks caused by O157 remain a public health concern. Cattle are the primary reservoir for O157, which colonizes the intestinal tract without inducing any overt clinical symptoms. O157 colonization is a major risk factor for carcass contamination at slaughter. Vaccination of cattle is an important tool to limit colonization and fecal shedding of O157, the outcomes essential for controlling downstream environmental and carcass contamination, and limiting zoonotic transmission to humans. Parenteral vaccination can reduce O157 shedding in cattle after challenge, although the impact of vaccination and vaccine formulation on cellular and mucosal immune responses are undetermined. To better characterize the cattle immune response to O157 vaccination, cattle were vaccinated with either water-in-oil-adjuvanted, formalin-inactivated hha ¬deletion mutant of shiga toxin 2 negative (stx2-) O157 (Adj-Vac); non-adjuvanted, formalin-inactivated hha deletion mutant of stx2- O157 (NoAdj-Vac); or non-vaccinated (NoAdj-NoVac) and peripheral O157-specific T cell and mucosal antibody responses assessed. Cattle in Adj-Vac group had a higher percentage of O157-specific IFN gamma producing CD4 plus and gamma delta plus T cells in recall assays compared to the NoAdj-Vac group. Furthermore, O157-specific IgA levels detected in feces of the Adj-Vac group were significantly lower in NoAdj-Vac group. Extracts prepared from Adj-Vac group feces, which contained O157-specific IgA, blocked O157 adherence to HEp-2 epithelial cells, but fecal extracts from NoAdj-Vac group did not block adherence. Taken together, these data suggest parenteral administration of adjuvanted, inactivated whole-cell vaccines for O157 can induce O157-specific cellular and mucosal immune responses that may be an important consideration for a successful vaccination scheme.