Northwestern University, Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL 60611, USA.
Future Microbiol. 2010 Aug;5(8):1289-96. doi: 10.2217/fmb.10.78.
Induction of protective immunity against pathogenic microbes, including Bacillus anthracis, requires efficient vaccines that potentiate antibody avidity and increase T-cell longevity. We recently reported that the delivery of targeted B. anthracis protective antigen (PA) genetically fused to a DC-binding peptide (DCpep) by Lactobacillus acidophilus induced mucosal and systemic immunity against B. anthracis challenge in mice.
MATERIALS & METHODS: Improvement of this oral vaccine strategy was attempted by use of the high copy and genetically stable q-replicating vector, pTRKH2, for expression of the targeted PA fusion protein in Lactobacillus gasseri, a common human commensal microbe, to vaccinate animals against anthrax Sterne infection.
Oral application of L. gasseri expressing the PA-DCpep fusion proteins elicited robust PA-neutralizing antibody and T-cell mediated immune responses against anthrax Sterne challenge, resulting in complete animal survival. Collectively, this improved expression vaccine strategy reduced the number of inoculations and length of the boosting period, leading to animal protection via efficacious bacterial adjuvanticity and safe oral delivery of this vaccine to mucosal immune cells, including dendritic cells.
Lactobacillus-based delivery offers tremendous practical advantages. Recombinant antigens such as PA would not require chemical coupling agents, and the recombinant bacteria can be administered orally where upon both mucosal and systemic immune responses are elicited.
诱导针对致病性微生物（包括炭疽芽孢杆菌）的保护性免疫需要有效的疫苗，这些疫苗能够增强抗体亲和力并延长 T 细胞的寿命。我们最近报道，通过嗜酸乳杆菌递送靶向炭疽芽孢杆菌保护性抗原（PA）与树突细胞结合肽（DCpep）融合的基因，可以在小鼠中诱导针对炭疽芽孢杆菌挑战的黏膜和系统免疫。
尝试通过使用高拷贝数和遗传稳定的 q 复制载体 pTRKH2 在格氏乳杆菌中表达靶向 PA 融合蛋白，改进这种口服疫苗策略，格氏乳杆菌是一种常见的人类共生微生物，用于对动物进行炭疽芽孢杆菌感染的疫苗接种。
口服表达 PA-DCpep 融合蛋白的格氏乳杆菌引发了针对炭疽芽孢杆菌 Sterne 挑战的强大的 PA 中和抗体和 T 细胞介导的免疫反应，导致动物完全存活。总的来说，这种改进的表达疫苗策略减少了接种次数和加强期的长度，通过有效的细菌佐剂和这种疫苗对黏膜免疫细胞（包括树突状细胞）的安全口服递送，实现了动物保护。
基于乳杆菌的递送提供了巨大的实际优势。重组抗原（如 PA）不需要化学偶联剂，并且可以口服给予重组细菌，从而引发黏膜和系统免疫反应。
