Co-immunization with two recombinant Eimeria tenella lines expressing immunoprotective antigens of E. maxima elicits enhanced protection against E. maxima infection

Abstract

Background Live anticoccidial vaccines have been a tremendous success for disease prevention. The establishment of the reverse genetic manipulation platform has enabled the development of Eimeria parasites, the live anticoccidial vaccine strains, as vaccine vectors. In our previous study, recombinant E. tenella expressing a single immunodominant antigen of E. maxima (Et-EmIMP1) was able to protect chickens against challenge infection with E. maxima . This promising result encouraged us to further explore strategies to improve the protection efficacy of recombinant Eimeria and develop it as a vaccine vector. Results We constructed a novel recombinant Eimeria line expressing apical membrane antigen 1 of E. maxima (Et-EmAMA1) and then immunized chickens with Et-EmAMA1 and/or Et-EmIMP1. We found that the E. maxima soluble antigen-specific cell-mediated immunity was much stronger in the birds that were co-immunized with Et-EmAMA1 and Et-EmIMP1 than in those that were immunized with Et-EmAMA1 or Et-EmIMP1 alone. The oocyst production after E. maxima infection was significantly reduced in the recombinant Eimeria -immunized birds compared with the wild-type-immunized and naïve birds. The oocyst production in the birds co-immunized with Et-EmAMA1 and Et-EmIMP1 was consistently the lowest among the treatment groups after E. maxima infection. Conclusions These results demonstrated that Eimeria is an effective vaccine vector that can carry and deliver heterologous Eimeria antigens to the host immune system and trigger specific immune responses. Our results also suggested that increasing the number of recombinant Eimeria lines is an effective approach to enhance protective immunity against infections with heterologous pathogens.

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

“…In the case of E. maxima, previous studies have described the occurrence of different local immune responses after challenge, with IFN-γ mRNA levels peaking after the first infection and being almost unaffected by subsequent infections [33]. We observed the same response in Emax-Emax chickens after secondary infection (low IFN-γ mRNA levels, similar to This finding is supported by a previous study, where vaccination with Et[EmAMA1] + Et[EmIMP1] was enough to induce specific IFN-γ responses after stimulation of PBMCs with E. maxima extracts [13]. We also measured IL-10 levels in the intestine since this cytokine has been correlated with susceptibility to E. maxima infection, possibly through inhibition of IFN-γ synthesis [34,35].…”

“…Prior to E. maxima challenge growth performance was comparable between vaccinated and non-vaccinated chickens, supporting our previous findings with regards to vaccine safety [11] [11][12][13]18].…”

Recombinant Lactococcus lactis co-expressing dendritic cell target peptide and E. tenella 3-1E protein: immune response and efficacy against homologous challenge

“…reflected by drug-resistant Eimeria species, drug residues in poultry products and the reversion to virulence for attenuated vaccines. The exploration of novel vaccines has become research hot point, and several delivery tools have been used to deliver target Eimeria proteins, including Escherichia coli (Yin et al, 2015), Bacillus subtilis (Lin et al, 2015), Mycobacterium bovis Bacillus Calmette-Guerin (Wang et al, 2014), attenuated Salmonella enterica serovar Typhimurium (Konjufca, Jenkins, Wang, Juarez-Rodriguez, & Curtiss, 2008), Pichia pastoris (Chen et al, 2015), fowlpox virus (Yang et al, 2008), tobacco (Sathish et al, 2011), nanoparticles (Jenkins et al, 2018;Zhang et al, 2012), Lactobacillus plantarum (Yang et al, 2017), Lactococcus lactis (Li et al, 2018;Ma et al, 2013;Ma et al, 2017), recombinant Eimeria (Tang et al, 2019). Based on our previous study using lactic acid bacteria as a delivery tool, we postulate that the immune responses and efficacies provided by oral immunization of recombinant lactococci could be improved by introducing immune enhancers into the live recombinant bacteria.…”

Towards Innovative Design and Application of Recombinant Eimeria as a Vaccine Vector

“…Immunization with recombinant Eimeria expressing either EmIMP1 or EmAMA1 can reduce oocyst production after the heterologous E. maxima challenge (29,46). The protection against heterologous pathogen infection was enhanced when coimmunized with double-recombinant Eimeria lines (47). Use of Eimeria as vaccine vector expressing immunoprotective antigens from heterologous Eimeria species represents the first instance of cross-protection against different Eimeria species by immunization with one species of Eimeria and opens a new avenue for developing coccidiosis vaccines.…”

“…Partial protection against a heterologous pathogen can be provided by recombinant E. tenella expressing the target antigen. As various Eimeria species parasitize on different sites of the intestine, specific antigens expressed by the four or more Eimeria species and coimmunization with the mixed recombinant Eimeria species offer a promising way for improving the protection against target pathogens (47). Thus, establishment of the transfection platform on other species, especially E. maxima, the most immunogenic species among chicken coccidia, is extremely urgent.…”