Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Future Microbiol. 2011 May;6(5):583-93. doi: 10.2217/fmb.11.32.
Using genetically engineered lactobacilli, producing high avidity llama VHH domains (referred to as anti-rotavirus proteins; ARPs), to test the effect of multimeric antibody fragments as prophylaxis and therapy against rotavirus infection.
Two ARPs, ARP1 and ARP3, shown to bind to different epitopes and act synergistically against rotavirus, were displayed on the surface of Lactobacillus paracasei as monovalent or bivalent proteins (mono- or bi-specific).
Although a nonsignificant difference was observed between lactobacilli producing bispecific ARP3-ARP1 and monomeric ARPs, lactobacilli producing bispecific ARP3-ARP1 were superior at reducing the rate of diarrhea when used for prophylactic and therapeutic intervention in a mouse model of rotavirus infection in comparison to nontreated animals.
Expression of bispecific antibodies in lactobacilli resulted in slight improvement of their efficacy. Furthermore, increasing the specificity would theoretically reduce the rate of appearance of viral escape mutants and would have a broader capacity to be effective against a range of viral serotypes.
使用基因工程乳杆菌生产高亲和力的 llama VHH 结构域（称为抗轮状病毒蛋白；ARPs），以测试多价抗体片段作为轮状病毒感染预防和治疗的效果。
两种 ARP，ARP1 和 ARP3，被证明能结合不同的表位并对轮状病毒发挥协同作用，被展示在副干酪乳杆菌表面作为单价或双价蛋白（单特异性或双特异性）。
尽管生产双特异性 ARP3-ARP1 和单克隆 ARP 的乳杆菌之间没有观察到显著差异，但与未治疗的动物相比，在轮状病毒感染的小鼠模型中进行预防和治疗干预时，生产双特异性 ARP3-ARP1 的乳杆菌在降低腹泻发生率方面更具优势。
在乳杆菌中表达双特异性抗体可略微提高其疗效。此外，提高特异性理论上会降低病毒逃逸突变体出现的速度，并具有更广泛的效力，可有效对抗一系列病毒血清型。
