Vaccination with killed whole-cells of Escherichia coli O157:H7 hha mutant emulsified with an adjuvant induced vaccine strain-specific serum antibodies and reduced E. coli O157:H7 fecal shedding in cattle

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

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/3/2018
Publication Date: 4/20/2018
Citation: Sharma, V.K., Schaut, R.G., Loving, C.L. 2018. Vaccination with killed whole-cells of Escherichia coli O157:H7 hha mutant emulsified with an adjuvant induced vaccine strain-specific serum antibodies and reduced E. coli O157:H7 fecal shedding in cattle. Veterinary Microbiology. 219:190-199. https://doi.10.1016/j.vetmic.2018.04.003.
DOI: https://doi.org/10.1016/j.vetmic.2018.04.003

Interpretive Summary: Escherichia coli O157 bacteria are commonly found in the digestive tract of cattle and are shed in their feces, resulting in contamination of animal hides and carcasses during animal processing. Fecal runoff containing O157 bacteria is also a risk factor in contamination of water and other foods, such as produce and fruits. Most human O157 infections occur through the consumption of contaminated food products. Vaccination of cattle is considered an important option for reducing the risk of O157 contamination of foods, and thus reducing human illnesses. In the current study, we have shown that the two doses of an inactivated vaccine prepared from a specific strain of O157 enhanced cattle immunity against O157, and reduced fecal shedding of O157. Thus, vaccine formulation does impact efficacy, and provides a mechanism of limiting environmental contamination.

Technical Abstract: Escherichia coli O157:H7 (O157) can cause from a mild diarrheal illness to hemorrhagic colitis and hemolytic uremic syndrome in humans. Cattle are the primary reservoir for O157 and fecal shedding of O157 by these animals is a major risk factor in contamination of cattle hides and carcasses at slaughter. Vaccination is an important strategy to reduce fecal shedding of O157 in cattle. In this study, we evaluated the immunogenicity and efficacy of an inactivated vaccine strain of O157 formulated with an adjuvant. This vaccine strain was deleted of the hha gene enabling high level expression of the locus of enterocyte effacement (LEE) encoded proteins required for O157 colonization in cattle. The inactivated vaccine strain emulsified with the adjuvant or suspended in the phosphate-buffered saline (PBS) was injected in the neck muscles of two groups of weaned calves followed by a booster three weeks later with the corresponding formulation. Animals in groups 3 and 4 were injected similarly with the adjuvant and PBS, respectively. All animals were orally inoculated three weeks post-booster vaccination with a live culture of O157. The animals vaccinated with the adjuvanted vaccine showed higher serum antibody titers to the vaccine strain and shed O157 for a shorter duration and at lower numbers compared to the animals vaccinated with the non-adjuvanted vaccine, adjuvant-only, or PBS. Western blotting of the vaccine strain lysates showed higher immunoreactivity of serum IgG in vaccinated animals to several O157-specific proteins and lipopolysaccharides (LPS). The vaccination induced IgG showed specificity to LEE-encoded proteins and outer membrane LPS as LEE and waaL deletion mutants, unable to produce LEE proteins and synthesize high molecular weight LPS, respectively, yielded significantly lower antibody titers compared to the parent vaccine strain. The positive reactivity of the immune serum was also observed for purified LEE-encoded proteins EspA and EspB. In conclusion, the results of this animal study showed that a two-dose regimen of an adjuvanted vaccine is capable of inducing O157-specific immune response that directly or indirectly reduced fecal shedding of O157 in cattle.