Hazama M, Takaoki M, Ohfune K, Hinuma S, Fujisawa Y
Biotechnology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Vaccine. 1989 Dec;7(6):567-73. doi: 10.1016/0264-410x(89)90285-5.
Genetically modified M (pre-S2+S; P31) protein (M-P31c) particles were formulated into a vaccine (TGP-943) through adsorption on to an alum adjuvant. The immunogenicity of this vaccine was investigated using guinea-pigs and various kinds of mice. In terms of anti-HBs(S) response, TGP-943 was found to be as immunogenic as the control plasma-derived vaccine (PDV) and yeast-derived S vaccine (YDSV) in Balb/c mice. TGP-943 induced anti-S antibodies even in S low-responder mice. In addition to the anti-S antibodies, TGP-943 was shown to elicit anti-pre-S2 antibodies dose-dependently, and the anti-pre-S2 antibodies were maintained at a high level after immunization with a high dose of TGP-943. The antibody response to pre-S2 had a tendency to appear earlier than that to S. M-P31c particles induced in vitro proliferation of TGP-943-primed lymph node cells, indicating that TGP-943 is more immunogenic than conventional vaccines in terms of T-cell levels. These results suggest that TGP-943 would be a promising candidate for a third generation hepatitis B vaccine.
将基因工程改造的M（前S2+S；P31）蛋白（M-P31c）颗粒吸附于明矾佐剂上制成疫苗（TGP-943）。使用豚鼠和各类小鼠研究了该疫苗的免疫原性。就抗-HBs（S）反应而言，发现TGP-943在Balb/c小鼠中的免疫原性与对照血浆源性疫苗（PDV）和酵母源性S疫苗（YDSV）相当。TGP-943甚至能在S低反应小鼠中诱导产生抗-S抗体。除抗-S抗体外，TGP-943还能剂量依赖性地引发抗前S2抗体，且在用高剂量TGP-943免疫后，抗前S2抗体维持在较高水平。对前S2的抗体反应往往比对S的抗体反应出现得更早。M-P31c颗粒能诱导经TGP-943致敏的淋巴结细胞在体外增殖，表明TGP-943在T细胞水平上比传统疫苗更具免疫原性。这些结果表明，TGP-943有望成为第三代乙肝疫苗的候选产品。
