Lessard Philip A, Parker Matthew, Bougri Oleg, Shen Binzhang, Samoylov Vladimir, Broomhead Jon, Li Xuemei, Raab R Michael
Agrivida, Inc., Woburn, MA, USA.
Unum Therapeutics, Cambridge, MA, USA.
Nat Food. 2020 Feb;1(2):119-126. doi: 10.1038/s43016-020-0029-6. Epub 2020 Feb 10.
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.
抗生素耐药性对人类和动物健康构成重大挑战，开发有效的无抗生素治疗方法是帮助减轻微生物耐药性的一项策略。全球家禽业面临着由艾美耳球虫引起的球虫病带来的日益严峻的挑战，球虫病是鸡的一种严重肠道疾病，目前需要使用离子载体抗生素进行治疗。艾美耳球虫刺激受感染鸡的小肠和盲肠中白细胞介素-10（IL-10）的表达，抑制其免疫反应并促进疾病进展。研究人员开发了用鸡IL-10（cIL-10）免疫的美洲驼产生的单域抗体，这些抗体在体外与cIL-10结合，阻断cIL-10受体结合，并诱导被cIL-10抑制的原代鸡脾细胞分泌干扰素γ（IFN-γ）。在转基因玉米中表达的单域抗体在表型正常的植物中显示出显著积累。当喂给受艾美耳球虫攻击的鸡时，转基因玉米显著提高了体重增加（与盐霉素处理的动物相同），使饲料转化率恢复正常（与未感染的对照动物相同水平），将柔嫩艾美耳球虫病变评分降低到盐霉素处理的对照动物的水平，并将卵囊数量减少到低于未治疗的感染对照动物的水平。在此，我们提出转基因玉米可能在减少家禽生产中抗生素的使用以及维持动物健康和生产力方面发挥作用，并可能有助于应对全球抗生素耐药性问题。
