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Improved performance of Eimeria-infected chickens fed corn expressing a single-domain antibody against interleukin-10

Nature Food volume 1, pages 119–126 (2020)Cite this article

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Abstract

Antimicrobial resistance is a significant challenge for human and animal health, and developing effective antibiotic-free treatments is a strategy to help mitigate microbial resistance. The global poultry industry faces growing challenges from Eimeria-induced coccidiosis, a serious enteric disease of chickens that currently requires treatment using ionophore antibiotics. Eimeria stimulates interleukin-10 (IL-10) expression in the small intestine and caecum of infected chickens, suppressing their immune response and facilitating disease progression. Single-domain antibodies raised from llamas immunized with chicken IL-10 (cIL-10) were developed that bind cIL-10 in vitro, block cIL-10 receptor binding and induce interferon gamma (IFN-γ) secretion from cIL-10-repressed primary chicken splenocytes. Single-domain antibodies expressed in transgenic corn demonstrated significant accumulation in phenotypically normal plants. When fed to Eimeria-challenged chickens, the transgenic corn significantly improved body weight gain (equal to that of salinomycin-treated animals), normalized the feed conversion ratio (to the same level as uninfected control animals), lowered E. tenella lesion scores to those of salinomycin-treated control animals, and reduced oocyst counts below those of infected untreated control animals. Here, we propose that transgenic corn may have a role in reducing the use of antibiotics in poultry production and maintaining animal health and productivity, and may contribute to efforts against global antimicrobial resistance.

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Fig. 1: In vitro analysis of candidate anti-cIL-10 antibodies.
Fig. 2: Comparison of two candidate sdAbs for transformation into corn.
Fig. 3: Temperature resilience of the candidate AgThG11 antibody.
Fig. 4: Transformation of corn with genes expressing the AgThG11 antibody.
Fig. 5: Inclusion of grain that expresses sdAb AgThG11 in the diet helps birds overcome the effects of a coccidiosis challenge.

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Data availability

Source data for Figs. 1, 3 and 5 are provided with the paper. Data from these studies are available through Figshare (www.figshare.com) at https://doi.org/10.6084/m9.figshare.10286153.v1.

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Acknowledgements

We acknowledge the contributions of the following scientists: A. Lee (ProSci); K. Wilhelmsen (Marin Biologic); L. Bartlett (University of Massachusetts Biophysical Characterization Facility); B. Lumpkins and G. Mathis (Southern Poultry Feed and Research).

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Author notes

  1. Binzhang Shen

    Present address: Unum Therapeutics, Cambridge, MA, USA

  2. Jon Broomhead

    Present address: Perstop US, St Louis, MO, USA

Authors and Affiliations

  1. Agrivida, Inc., Woburn, MA, USA

    Philip A. Lessard, Matthew Parker, Oleg Bougri, Binzhang Shen, Vladimir Samoylov, Jon Broomhead, Xuemei Li & R. Michael Raab

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Contributions

P.A.L. led the antibody discovery programme, led the cell-based assay development and performance, managed analytical development, helped transplant, water and harvest plants, milled transgenic grain for use in the feeding studies, and reviewed and edited the manuscript. M.P. characterized the antibodies in vitro and in the cell-based assay, which required microbial antibody and IL-10r soluble-domain production, performed Biacore experiments, performed western blots and reviewed the manuscript. O.B. conducted all gene design and synthesis, constructed transformation vectors, helped genotype transgenic plants, developed the ELISA assay, performed ELISAs, measured the thermal stability of the antibodies, and reviewed and edited the manuscript. B.S. conducted western blot analysis, helped develop the ELISA assay, performed ELISAs and reviewed the manuscript. V.S. conducted plant transformation and plant tissue culture, generated all transgenic events, managed and conducted plant production, and reviewed the manuscript. J.B. led the animal challenge studies and reviewed the manuscript. X.L. helped transplant, water and harvest plants, conducted assays, and reviewed and edited the manuscript. R.M.R. developed the overall research plan and strategy, managed and coordinated studies between groups, prioritized antibodies for development, helped transplant, water and harvest plants, drafted the initial paper, and reviewed and approved the final manuscript.

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Correspondence to R. Michael Raab.

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The authors declare the following competing interests: employment at Agrivida, Inc.

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Lessard, P.A., Parker, M., Bougri, O. et al. Improved performance of Eimeria-infected chickens fed corn expressing a single-domain antibody against interleukin-10. Nat Food 1, 119–126 (2020). https://doi.org/10.1038/s43016-020-0029-6

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