Wen Ke, Liu Fangning, Li Guohua, Bai Muqun, Kocher Jacob, Yang Xingdong, Wang Haifeng, Clark-Deener Sherrie, Yuan Lijuan
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg.
J Pediatr Gastroenterol Nutr. 2015 Jun;60(6):834-43. doi: 10.1097/MPG.0000000000000694.
The use of immunostimulatory strains of probiotics as adjuvants has been increasingly recognized as a promising approach in enhancing vaccine immunogenicity; however, dose effects of probiotic adjuvants are not well defined. In the present study, we examined dose effects of a commonly used probiotic strain, Lactobacillus rhamnosus GG (LGG), on immunomodulation with 2 different dosages.
Neonatal gnotobiotic pigs were inoculated with 2 oral doses of attenuated human rotavirus (AttHRV) vaccines and fed with 5 doses (LGG5X; total 2.1 × 10(6) colony-forming units) or 9 doses (LGG9X; total 3.2 × 10(6) colony-forming units) of LGG, starting at 3 days of age.
Both LGG feeding regimens enhanced the protection rate of AttHRV vaccine against diarrhea on virulent human rotavirus challenge. LGG5X, but not LGG9X, significantly enhanced rotavirus-specific intestinal memory B-cell responses to AttHRV; LGG5X also significantly enhanced virus-specific intestinal immunoglobulin A (IgA) antibody-secreting cell responses. Both regimens significantly enhanced rotavirus-specific serum IgA antibody responses to AttHRV. They also enhanced rotavirus-specific interferon-γ-producing effector/memory T-cell responses to AttHRV vaccine, with LGG9X being more effective than LGG5X, and both regimens downregulated CD4+CD25-FoxP3+ regulatory T (Treg) cell responses in most lymphoid tissues examined prechallenge and postchallenge and maintained the CD4+CD25+FoxP3+ Treg population in the ileum and intraepithelial lymphocyte postchallenge. LGG9X, however, did not significantly reduce total CD4+CD25-FoxP3+ Treg frequencies in the intestine and transforming growth factor-β-producing and interleukin (IL)-10-producing Treg frequencies in the blood.
These results indicate that LGG at both dosages functioned as effective probiotic adjuvant for AttHRV vaccine, but different dosages differentially modulated immune responses to favor either the mucosal IgA response (LGG5X) or the T-cell response (LGG9X).
将免疫刺激性益生菌菌株用作佐剂已日益被认为是增强疫苗免疫原性的一种有前景的方法；然而，益生菌佐剂的剂量效应尚未明确界定。在本研究中，我们用两种不同剂量研究了常用益生菌菌株鼠李糖乳杆菌GG（LGG）的剂量效应。
新生无菌仔猪接种两剂口服减毒人轮状病毒（AttHRV）疫苗，并从3日龄开始喂食5剂（LGG5X；共2.1×10⁶ 菌落形成单位）或9剂（LGG9X；共3.2×10⁶ 菌落形成单位）的LGG。
两种LGG喂养方案均提高了AttHRV疫苗对毒力人轮状病毒攻击所致腹泻的保护率。LGG5X显著增强了对AttHRV的轮状病毒特异性肠道记忆B细胞反应，但LGG9X未增强；LGG5X还显著增强了病毒特异性肠道免疫球蛋白A（IgA）抗体分泌细胞反应。两种方案均显著增强了对AttHRV的轮状病毒特异性血清IgA抗体反应。它们还增强了对AttHRV疫苗的轮状病毒特异性产生干扰素-γ的效应/记忆T细胞反应，LGG9X比LGG5X更有效，并且两种方案在攻击前和攻击后检查的大多数淋巴组织中均下调了CD4⁺CD25⁻FoxP3⁺调节性T（Treg）细胞反应，并在攻击后维持了回肠和上皮内淋巴细胞中的CD4⁺CD25⁺FoxP3⁺Treg群体。然而，LGG9X并未显著降低肠道中总的CD4⁺CD25⁻FoxP3⁺Treg频率以及血液中产生转化生长因子-β和产生白细胞介素（IL）-10的Treg频率。
这些结果表明，两种剂量的LGG均作为AttHRV疫苗的有效益生菌佐剂发挥作用，但不同剂量对免疫反应的调节存在差异，有利于黏膜IgA反应（LGG5X）或T细胞反应（LGG9X）。
