Stoute J A, Ballou W R, Kolodny N, Deal C D, Wirtz R A, Lindler L E
Department of Medicine, Walter Reed Army Medical Center, Washington, D.C. 20307.
Infect Immun. 1995 Mar;63(3):934-9. doi: 10.1128/iai.63.3.934-939.1995.
The mouse monoclonal antibody 2A10 (immunoglobulin G), which recognizes the (NANP)n repeat of Plasmodium falciparum circumsporozoite surface protein, was used to screen a filamentous phage epitope library expressing random amino acid hexamers. The sequences obtained were TNRNPQ, SNRNPQ, NND-NPQ, SNYNPQ, and QNDNPQ (single-letter amino acid designation). These peptides showed 50% homology with the native epitope (PNANPN) and therefore were considered to mimic its structure (mimotopes). Two of these mimotopes (TNRNPQ and NNDNPQ) inhibited the binding of monoclonal antibody 2A10 to the recombinant protein R32LR, which contains the amino acid sequence [(NANP)15NVDP]2. Immunization of mice and rabbits using the peptide (TNRNPQ)4 induced a humoral response that recognized R32LR by an enzyme-linked immunosorbent assay and P. falciparum sporozoites by an immunofluorescence assay. These results suggest that phage epitope libraries can be exploited to screen for mimotopes in the design of subunit vaccines against infectious agents.
小鼠单克隆抗体2A10（免疫球蛋白G）可识别恶性疟原虫环子孢子表面蛋白的（NANP）n重复序列，用于筛选表达随机氨基酸六聚体的丝状噬菌体表位文库。获得的序列为TNRNPQ、SNRNPQ、NNDNPQ、SNYNPQ和QNDNPQ（单字母氨基酸命名）。这些肽与天然表位（PNANPN）具有50%的同源性，因此被认为模拟了其结构（模拟表位）。其中两个模拟表位（TNRNPQ和NNDNPQ）抑制了单克隆抗体2A10与重组蛋白R32LR的结合，R32LR包含氨基酸序列[(NANP)15NVDP]2。用肽（TNRNPQ）4免疫小鼠和兔子可诱导体液反应，通过酶联免疫吸附测定法可识别R32LR，通过免疫荧光测定法可识别恶性疟原虫子孢子。这些结果表明，在设计针对感染因子的亚单位疫苗时，可利用噬菌体表位文库筛选模拟表位。
