Toward improved vaccines for control of avian pathogenic Escherichia coli in poultry

Avian pathogenic Escherichia coli (APEC) comprise a diverse group of enteric bacteria that cause colibacillosis, a severe and recalcitrant disease of poultry that exerts substantial economic and welfare costs upon producers worldwide. Losses are realised through increased mortality, condemnation of carcasses at processing, reduced feed conversion efficiency and costs associated with prophylaxis and treatment. Poultry health is considered vital to the supply and safety of food to a fast growing and increasingly affluent global population and APEC are a persistent impediment to productivity. Colibacillosis is common in birds subject to stress associated with poor husbandry, formation of a social hierarchy, concurrent infections or at the onset of laying. Field data indicate a higher incidence of colibacillosis in poultry reared under free-range systems and consumer demand for such produce, coupled with the abolition of traditional cages in egg production by 2012 (EU Directive 1999/74/EC1) is expected to increase the incidence of disease. Control of colibacillosis with antibiotics is hampered by the existence and transfer of multiple drug resistance traits among pathogenic strains. Additionally, antibiotic use is prohibited in layers and broilers close to slaughter to prevent residues entering the human food chain. Of the other available options for control, vaccination is considered to be the most viable. In most countries, outbreaks of avian colibacillosis are controlled using vaccines comprising whole cells of the outbreak strain inactivated with formalin, however immunity is short-lived and strain-specific. A live-attenuated vaccine has recently been licensed in the USA for use in poultry, but extensive field efficacy data are lacking. It is not understood how these vaccines work or why long-lasting cross-protective responses remain elusive. In order to improve existing vaccines, we first need to dissect the mechanisms involved in the immunity they confer in target food-producing hosts. With cash and in-kind contributions from the poultry sector, we therefore propose to vaccinate turkeys with existing killed and live vaccines and describe; i) immune responses correlated with protection induced by vaccination; ii) whether prior infection can protect against re-infection and if so, by what mechanisms; iii) the role of antibody and antibody-producing cells in protection; iv) whether protective immune responses can be improved using preparations (adjuvants) that potentiate specific immune responses. Collectively, such information will lay the foundations for rational design of improved vaccines that elicit responses of an appropriate nature, location and duration.

Colibacillosis is the most common infectious disease of farmed poultry. It is caused by avian pathogenic E. coli (APEC) and is frequently associated with concurrent respiratory viral or mycoplasma infections, immuno-suppression and stress. Substantial economic losses are incurred worldwide as a consequence of mortality, condemnation of carcasses, reduced yield, treatment and prophylaxis. Infections are severe and profoundly impair animal welfare, food security and prosperity. Control of the disease by antibiotic therapy is prohibited in food-producing stock owing to entry of residues into the food chain. Existing vaccines based on autogenous bacterins confer limited and serotype-specific protection. A US-licenced live-attenuated vaccine offers protection against other serotypes in experimental models, but field data are lacking. A pressing need exists for improved vaccines that confer longer-lasting cross-protective immunity against prevailing serotypes. Toward the rational design of such vaccines, we propose to unravel avian immune responses associated with vaccine-mediated protection and clearance following primary and secondary infection. We will address the hypothesis that inactivated vaccines act predominantly by raising humoral immunity, whilst live vaccines stimulate cell-mediated responses. In addition to quantifying the timing, location and magnitude of effector and innate responses, we will evaluate the role played by antibody and B-cells by bursectomy and passive transfer. This will provide valuable data on how a predominantly extracellular pathogen is controlled in poultry, enabling comparative analysis with data accrued at IAH on control of invasive Salmonella serovars. Using knowledge accumulated from the proposed studies, we will assess the impact on bacterin efficacy of potentiating specific responses using Th1- or Th2-biasing adjuvants. The potential impact of the research is reflected in the cash and in-kind contributions of the poultry sector.