Vaccination with transgenic Eimeria tenella expressing Eimeria maxima AMA1 and IMP1 confers partial protection against high-level E. maxima challenge in a broiler model of coccidiosis

Abstract

Background: Poultry coccidiosis is a parasitic enteric disease with a highly negative impact on chicken production. In-feed chemoprophylaxis remains the primary method of control, but the increasing ineffectiveness of anticoccidial drugs, and potential future restrictions on their use has encouraged the use of commercial live vaccines. Availability of such formulations is constrained by their production, which relies on the use of live chickens. Several experimental approaches have been taken to explore ways to reduce the complexity and cost of current anticoccidial vaccines including the use of live vectors expressing relevant Eimeria proteins. We and others have shown that vaccination with transgenic Eimeria tenella parasites expressing Eimeria maxima Apical Membrane Antigen-1 or Immune Mapped Protein-1 (EmAMA1 and EmIMP1) partially reduces parasite replication after challenge with a low dose of E. maxima oocysts. In the present study, we have reassessed the efficacy of these experimental vaccines using commercial birds reared at high stocking densities and challenged with both low and high doses of E. maxima to evaluate how well they protect chickens against the negative impacts of disease on production parameters. Methods: Populations of E. tenella parasites expressing EmAMA1 and EmIMP1 were obtained by nucleofection and propagated in chickens. Cobb500 broilers were immunised with increasing doses of transgenic oocysts and challenged two weeks later with E. maxima to quantify the effect of vaccination on parasite replication, local IFN-γ and IL-10 responses (300 oocysts), as well as impacts on intestinal lesions and body weight gain (10,000 oocysts). Results: Vaccination of chickens with E. tenella expressing EmAMA1, or admixtures of E. tenella expressing EmAMA1 or EmIMP1, was safe and induced partial protection against challenge as measured by E. maxima replication and severity of pathology. Higher levels of protection were observed when both antigens were delivered and was associated with a partial modification of local immune responses against E. maxima, which we hypothesise resulted in more rapid immune recognition of the challenge parasites.

Chicken Coccidiosis: From the Parasite Lifecycle to Control of the Disease

“…However, one major constraint in deployment of such antigen-specific vaccines is an appropriate and effective delivery system (51). Several possible vectors for oral administration, including Bacillus, Salmonella, transgenic Eimeria and yeasts such as Saccharomyces cerevisiae, are currently in development and could be appropriate (51,129,130).…”

Cellular electron tomography of the apical complex in the apicomplexan parasite Eimeria tenella shows a highly organised gateway for regulated secretion

“…Three-week-old Lohmann chickens (purchased from APHA Weybridge) kept under specific pathogen free conditions were orally infected with 4,000 sporulated E. tenella Wisconsin strain oocysts (Shirley, 1995). Oocysts were harvested at 7 days post-infection and excystation and sporozoite purification performed as previously described (Pastor-Fernández et al, 2020).…”

Spotlight on avian pathology:Eimeriaand the disease coccidiosis

“…One major constraint in deployment of such antigen-specific vaccines is an appropriate and effective delivery system. Several possible vectors for oral administration, including Bacillus, Salmonella, transgenic Eimeria and yeasts such as Saccharomyces cerevisiae, are currently in development and could be appropriate (Hoelzer et al, 2018;Pastor-Fernández et al, 2020). Extension of these technologies to improve vaccines for turkeys will also be required.…”

“…New assays are also available for use in vivo, including sensitive species-specific quantitative PCR to measure parasite replication with higher throughput and greater reproducibility than traditional measures using microscopy (Nolan et al, 2015). Development of a tool kit for transient and stable genetic modification of Eimeria has complemented these advances, supporting studies of fundamental biology and vaccine development (Pastor-Fernández et al, 2019).…”