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

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.

KEYWORDS:

• Lactococcus lactis
• anti-inflammation
• allergy vaccine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The protocols used in the rabbit experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Taichung Veterans General Hospital (La -1081661).

Additional information

Funding

This study was supported by grants from Taichung Veterans General Hospital [grant nos. TCVGH-1077313C and 1087316C].