Preclinical Safety Evaluation of Engineered Lactococcus lactis NZ3900 Biotherapeutics Using a 13-Week Repeated Dose Oral Toxicity Study in Rabbits

IF 1.8 4区农林科学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Food Biotechnology Pub Date : 2023-07-03 DOI:10.1080/08905436.2023.2235421

Mey-Fann Lee, Yu-Wen Chu, C. Chiang, Rongrong Jiang, Wei Wen Lin, Nancy M Wang

引用次数: 0

Abstract

ABSTRACT Lactococcus lactis is one of the most important and safe microorganisms used in the dairy industry. Previously, we orally fed cholesterol-fed rabbits with recombinant Ling Zhi 8 (LZ8) protein from L. lactis NZ3900/pNZ8149 and showed anti-inflammatory effects during the development of fatty liver and atheroma. In order to generate a clinically effective oral immunotherapy for the treatment of allergy, L. lactis clones for Der p 2, Per a 2, and Cla c 14 were introduced into L. lactis NZ3900/pNZ8149 to obtain recombinant allergen-based vaccines. In this study, we developed a triple-antigen vaccine formulation, Lactis- IL-1Ra, Lactis-LZ8, Lactis-Triple, and evaluated their preclinical safety in rabbits by oral administration with repeated doses for 90 days. All of the rabbits survived the challenge without any adverse clinical signs or abnormal changes. A notable advantage of this vaccine is that it can be given orally, and thus self-administration at home would be feasible.

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工程乳酸乳球菌NZ3900生物治疗药物在家兔13周重复口服毒性研究中的临床前安全性评价

乳酸乳球菌是乳制品工业中最重要、最安全的微生物之一。在此之前，我们用乳酸乳杆菌NZ3900/pNZ8149重组灵致8 (LZ8)蛋白口服胆固醇饲养家兔，在脂肪肝和动脉粥样硬化的发展过程中显示出抗炎作用。为了产生临床有效的口服免疫疗法治疗过敏，将乳酸菌Der p2、Per a2和cla14克隆引入乳酸菌NZ3900/pNZ8149中，获得重组变应原疫苗。在这项研究中，我们开发了一种三抗原疫苗制剂，Lactis- IL-1Ra, Lactis- lz8, Lactis- triple，并通过重复给药90天，评估了它们在家兔身上的临床前安全性。所有的兔子都存活了下来，没有任何不良临床症状或异常变化。这种疫苗的一个显著优点是可以口服，因此在家中自行给药是可行的。

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来源期刊

Food Biotechnology 工程技术-生物工程与应用微生物

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Food Biotechnology is an international, peer-reviewed journal that is focused on current and emerging developments and applications of modern genetics, enzymatic, metabolic and systems-based biochemical processes in food and food-related biological systems. The goal is to help produce and improve foods, food ingredients, and functional foods at the processing stage and beyond agricultural production. Other areas of strong interest are microbial and fermentation-based metabolic processing to improve foods, food microbiomes for health, metabolic basis for food ingredients with health benefits, molecular and metabolic approaches to functional foods, and biochemical processes for food waste remediation. In addition, articles addressing the topics of modern molecular, metabolic and biochemical approaches to improving food safety and quality are also published. Researchers in agriculture, food science and nutrition, including food and biotechnology consultants around the world will benefit from the research published in Food Biotechnology. The published research and reviews can be utilized to further educational and research programs and may also be applied to food quality and value added processing challenges, which are continuously evolving and expanding based upon the peer reviewed research conducted and published in the journal.