Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY, USA.
Division of Pediatrics Infectious Diseases, Department of Pediatrics, University at Buffalo, Buffalo, NY, USA.
Biomed J. 2023 Dec;46(6):100588. doi: 10.1016/j.bj.2023.03.001. Epub 2023 Mar 15.
Enterotoxigenic Escherichia coli (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.
Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE.
Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.
These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.
肠毒素性大肠杆菌（ETEC）菌株通过表面表达的定植因子引起感染性腹泻，并在宿主肠道上皮定植。定植因子抗原 I（CFA/I）是一种常见的 ETEC 定植因子，是疫苗的靶点，因为针对该菌毛的抗体可以阻断 ETEC 的黏附和预防腹泻。
使用一种疫苗佐剂系统研究了两种源自 CFA/I 的重组抗原，该佐剂系统将可溶性抗原呈现在免疫脂质体的表面。第一种抗原 CfaEB 是 CFA/I 的小（CfaE）和大（CfaB）亚基的嵌合融合蛋白。第二种抗原 CfaEad 是 CfaE 的黏附结构域。
由于其 His 标签，重组 CfaEB 和 CfaEad 与含有钴卟啉磷脂（CoPoP）和合成单磷酰脂质 A（PHAD）佐剂的纳米脂质体混合时会自发结合。用亚微克剂量的 CfaEB 或 CfaEad 与 CoPoP/PHAD 脂质体混合，肌肉内免疫小鼠，可诱导血清 IgG 和肠道 IgA 抗体。较小的 CfaEad 抗原从脂质体展示中获益更多。用脂质体展示的 CfaEB 或 CfaEad 免疫的小鼠的血清和肠抗体通过免疫荧光和血凝抑制试验，用表达 CFA/I 菌毛的 H10407 ETEC 菌株证实可识别天然 CFA/I 菌毛。
这些数据表明，当以基于免疫原性颗粒的制剂递送时，定植因子衍生的重组 ETEC 抗原表现出免疫原性。
