{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T22:57:28Z","timestamp":1773097048606,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Avian coccidiosis is an intestinal parasitic disease exerting a highly negative impact on the global poultry industry. The aim of the present study is to evaluate the immune protective efficacies against <jats:italic>Eimeria tenella<\/jats:italic> infection in chickens orally immunized with combined recombinant probiotics <jats:italic>Entercoccus faecalis (E. faecalis)<\/jats:italic> delivering surface-anchored <jats:italic>E. tenella<\/jats:italic> proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four kinds of novel probiotics vaccines that surface<jats:italic>-<\/jats:italic>expressing four <jats:italic>Eimeria tenella<\/jats:italic> (<jats:italic>E. tenella<\/jats:italic>) proteins EtAMA1, EtIMP1, EtMIC2 and Et3-1E were produced, respectively. The expression of four target proteins on the surface of recombinant bacteria was detected by Western blot and indirect immunofluorescence assay (IFA). Then the four kinds of recombinant <jats:italic>E. faecalis<\/jats:italic> were combined to immunize chickens <jats:italic>via<\/jats:italic> oral route in different combinations. The immunizations were performed three times at two-week intervals, and each for three consecutive days. After immunizations, chickens in each immunized group were orally challenged with <jats:italic>E. tenella<\/jats:italic> sporulated oocysts. The immune responses and protective efficacies against homologous infection were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that three or four live recombinant <jats:italic>E. faecalis<\/jats:italic> induced effective antigen-specific humoral, intestinal mucosal immune responses, stimulated peripheral T lymphocytes proliferation, and displayed partial protections against homologous challenge as measured by cecal lesions, oocyst shedding, and body weight gain (BWG). Notably, higher levels of protective efficacies were observed when the four recombinant <jats:italic>E. faecalis<\/jats:italic> delivering target proteins were combined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Chickens orally administrated with three or four, especially the four combined recombinant <jats:italic>E. faecalis<\/jats:italic> stimulated specific immune responses, which provided anti-coccidial effects. This study offers an idea for future development of novel vaccines based on multi-antigens delivered by probiotic bacteria.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1042143","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T07:12:32Z","timestamp":1665645152000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Combined oral immunization with probiotics Entercoccus faecalis delivering surface-anchored Eimeria tenella proteins provide protective efficacies against homologous infection in chickens"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenjing","family":"Zhi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingrong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghui","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuju","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunli","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dexing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2021.110321","article-title":"Relationship between eimeria tenella associated-early clinical signs and molecular changes in the intestinal barrier function","volume":"240","author":"Pham","year":"2021","journal-title":"Vet Immunol immunopathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2021.101239","article-title":"Survey of coccidia on commercial broiler farms in Colombia: Frequency of eimeria species, anticoccidial sensitivity, and histopathology","volume":"100","author":"Mesa","year":"2021","journal-title":"Poult Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.00384","article-title":"Overview of poultry eimeria life cycle and host-parasite interactions","volume":"7","author":"L\u00f3pez-Osorio","year":"2020","journal-title":"Front vet Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2019.10.073","article-title":"Effects of eimeria tenella infection on the barrier damage and microbiota diversity of chicken cecum","volume":"99","author":"Zhou","year":"2020","journal-title":"Poult Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001282","article-title":"The c-terminus of toxoplasma Ron2 provides the crucial link between Ama1 and the host-associated invasion complex","volume":"7","author":"Tyler","year":"2011","journal-title":"PloS Pathog"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041115","article-title":"Identification and characterization of eimeria tenella apical membrane antigen-1 (Ama1)","volume":"7","author":"Jiang","year":"2012","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2007.09.013","article-title":"Rhoptries: An arsenal of secreted virulence factors","volume":"10","author":"Bradley","year":"2007","journal-title":"Curr Opin Microbiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.pt.2010.02.012","article-title":"Dissecting the apicomplexan rhoptry neck proteins","volume":"26","author":"Proellocks","year":"2010","journal-title":"Trends Parasitol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2020.107901","article-title":"A potential vaccine candidate towards chicken coccidiosis mediated by recombinant lactobacillus plantarum with surface displayed Etmic2 protein","volume":"215","author":"Huang","year":"2020","journal-title":"Exp Parasitol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.01.068","article-title":"Display of eimeria tenella Etmic2 protein on the surface of saccharomyces cerevisiae as a potential oral vaccine against chicken coccidiosis","volume":"32","author":"Sun","year":"2014","journal-title":"Vaccine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.vetpar.2017.07.025","article-title":"Humoral and cytokine response elicited during immunisation with recombinant immune mapped protein-1 (Etimp-1) and oocysts of eimeria tenella","volume":"244","author":"Kundu","year":"2017","journal-title":"Vet Parasitol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-015-4539-3","article-title":"Protective immunity against eimeria tenella infection in chickens following oral immunization with bacillus subtilis expressing eimeria tenella 3-1e protein","volume":"114","author":"Lin","year":"2015","journal-title":"Parasitol Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.exppara.2017.05.001","article-title":"Construction of lactococcus lactis expressing secreted and anchored eimeria tenella 3-1e protein and comparison of protective immunity against homologous challenge","volume":"178","author":"Ma","year":"2017","journal-title":"Exp Parasitol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2020.03.014","article-title":"Immune response and protective efficacy of recombinant enterococcus faecalis displaying dendritic cell-targeting peptide fused with eimeria tenella 3-1e protein","volume":"99","author":"Chen","year":"2020","journal-title":"Poult Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2010.06.010","article-title":"Studies on construction of a recombinant eimeria tenella So7 gene expressing escherichia coli and its protective efficacy against homologous infection","volume":"59","author":"Yang","year":"2010","journal-title":"Parasitol Int"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1637\/aviandiseases-D-19-00159","article-title":"Mucosal delivery of a self-destructing salmonella-based vaccine inducing immunity against eimeria","volume":"64","author":"Kong","year":"2020","journal-title":"Avian Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109061","article-title":"Prolonging and enhancing the protective efficacy of the Etmic3-C-Mar against eimeria tenella through delivered by attenuated salmonella typhimurium","volume":"279","author":"Zhao","year":"2020","journal-title":"Vet Parasitol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12934-020-1297-4","article-title":"Protective effects of a food-grade recombinant lactobacillus plantarum with surface displayed Ama1 and Etmic2 proteins of eimeria tenella in broiler chickens","volume":"19","author":"Liu","year":"2020","journal-title":"Microbial Cell fact"},{"key":"B19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13567-022-01045-w","article-title":"A multiepitope vaccine encoding four eimeria epitopes with plga nanospheres: A novel vaccine candidate against coccidiosis in laying chickens","volume":"53","author":"Yu","year":"2022","journal-title":"Vet Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":":e00888-17","DOI":"10.1128\/iai.00888-17","article-title":"Transgenic eimeria tenella expressing profilin of eimeria maxima elicits enhanced protective immunity and alters gut microbiome of chickens","volume":"86","author":"Tang","year":"2018","journal-title":"Infect Immun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1186\/s13071-020-04210-2","article-title":"Vaccination with transgenic eimeria tenella expressing eimeria maxima Ama1 and Imp1 confers partial protection against high-level e","volume":"13","author":"Pastor-Fern\u00e1ndez","year":"2020","journal-title":"Maxima Challenge Broiler Model Coccidiosis Parasites Vectors"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.919100","article-title":"Probiotics surface-delivering Fiber2 protein of fowl adenovirus 4 stimulate protective immunity against hepatitis-hydropericardium syndrome in chickens","volume":"13","author":"Jia","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.9.3068-3072.1997","article-title":"Cell wall anchoring of the streptococcus pyogenes M6 protein in various lactic acid bacteria","volume":"179","author":"Piard","year":"1997","journal-title":"J bacteriol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2010.07.015","article-title":"Vaccination of chickens with DNA vaccine encoding eimeria acervulina 3-1e and chicken il-15 offers protection against homologous challenge","volume":"127","author":"Ma","year":"2011","journal-title":"Exp Parasitol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exppara.2018.05.003","article-title":"Recombinant lactococcus lactis expressing eimeria tenella Ama1 protein and its immunological effects against homologous challenge","volume":"191","author":"Li","year":"2018","journal-title":"Exp Parasitol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109320","article-title":"Eimeria tenella: Imp1 protein delivered by lactococcus lactis induces immune responses against homologous challenge in chickens","volume":"289","author":"Ma","year":"2021","journal-title":"Vet Parasitol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.01.003","article-title":"Live recombinant lactococcuslactis expressing avian hepatitis virus Orf2 protein: Immunoprotection against homologous virus challenge in chickens","volume":"36","author":"Wang","year":"2018","journal-title":"Vaccine"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods (San Diego Calif)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(70)90063-9","article-title":"Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens","volume":"28","author":"Johnson","year":"1970","journal-title":"Exp Parasitol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2020.105417","article-title":"Transgenic eimeria parasite: A potential control strategy for chicken coccidiosis","volume":"205","author":"Fatoba","year":"2020","journal-title":"Acta tropica"},{"key":"B31","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1051\/parasite\/2020068","article-title":"Further investigation of the characteristics and biological function of eimeria tenella apical membrane antigen 1","volume":"27","author":"Wang","year":"2020","journal-title":"Parasite (Paris France)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.vetpar.2015.03.012","article-title":"Immunogenicity and protective efficacy of an eimeria vaccine candidate based on eimeria tenella immune mapped protein 1 and chicken Cd40 ligand","volume":"210","author":"Yin","year":"2015","journal-title":"Vet Parasitol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/0166-6851(96)02662-x","article-title":"Molecular cloning and characterization of a novel acidic microneme protein (Etmic-2) from the apicomplexan protozoan parasite, eimeria tenella","volume":"79","author":"Tomley","year":"1996","journal-title":"Mol Biochem Parasitol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.03.046","article-title":"Improving the immunogenicity and protective efficacy of the Etmic2 protein against eimeria tenella infection through random mutagenesis","volume":"36","author":"Chen","year":"2018","journal-title":"Vaccine"},{"key":"B35","doi-asserted-by":"publisher","first-page":":27","DOI":"10.3390\/medsci6020027","article-title":"Live bacterial vectors-a promising DNA vaccine delivery system","volume":"6","author":"Yurina","year":"2018","journal-title":"Med Sci (Basel Switzerland)"},{"key":"B36","article-title":"Lactococcus lactis : A new strategy for vaccination","volume":"9","author":"Azizpour","year":"2017","journal-title":"Avicenna J Med Biotechnol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7425","article-title":"Peptides identified through phage display direct immunogenic antigen to dendritic cells","volume":"172","author":"Curiel","year":"2004","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.vetpar.2017.01.023","article-title":"Construction and immunological evaluation of recombinant lactobacillus plantarum expressing So7 of eimeria tenella fusion dc-targeting peptide","volume":"236","author":"Yang","year":"2017","journal-title":"Vet Parasitol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.rvsc.2016.12.002","article-title":"Targeting antigens to Dec-205 on dendritic cells induces a higher immune response in chickens: Hemagglutinin of avian influenza virus example","volume":"111","author":"J\u00e1uregui-Z\u00fa\u00f1iga","year":"2017","journal-title":"Res vet Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"17214","DOI":"10.1038\/s41598-021-96527-w","article-title":"Differential responses of chicken monocyte-derived dendritic cells infected with salmonella gallinarum and salmonella typhimurium","volume":"11","author":"Singh","year":"2021","journal-title":"Sci Rep"},{"key":"B41","article-title":"The role of secretory iga in anti-coccidial immunity in the chicken","volume":"34","author":"Davis","year":"1978","journal-title":"Immunology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109032","article-title":"In vivo immunoprotective comparison between recombinant protein and DNA vaccine of eimeria tenella surface antigen 4","volume":"278","author":"Zhao","year":"2020","journal-title":"Vet Parasitol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2015.08.026","article-title":"Li X. partial protection against four species of chicken coccidia induced by multivalent subunit vaccine","volume":"212","author":"Song","year":"2015","journal-title":"Vet Parasitol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2006.07.007","article-title":"Analysis of chicken cytokine and chemokine gene expression following eimeria acervulina and eimeria tenella infections","volume":"114","author":"Hong","year":"2006","journal-title":"Vet Immunol immunopathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1042143\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T07:12:36Z","timestamp":1665645156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1042143\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2022.1042143"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1042143","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"article-number":"1042143"}}