Katkov W N, Watkins E, DeMelia H C, Dienstag J L
Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
J Viral Hepat. 1994;1(1):79-83. doi: 10.1111/j.1365-2893.1994.tb00065.x.
The product of the pre-S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S-gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the 'middle protein' gene product of pre-S2 plus S (pre-S vaccine). We compared the immunogenicity of three doses of the pre-S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax-HB); 87 seronegative adults were randomized to receive 12 micrograms (group 1), 24 micrograms (group 2), or 48 micrograms (group 3) of the pre-S vaccine or 10 micrograms of Recombivax-HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti-HBs) appeared after booster vaccination in > or = 94% of vaccinees. Immunogenicity was best in recipients of 48 micrograms of the pre-S vaccine and Recombivax-HB, and geometric mean titres (GMT) for the pre-S vaccine were higher than those for Recombivax-HB only at the pre-S vaccine dose of 48 micrograms (group 3). Antibody to pre-S2 developed in 75% of the pre-S2 vaccine recipients (not in Recombivax-HB recipients) within 7 months. These findings indicate that the pre-S vaccine is immunogenic in healthy adults but that a dose of 48 micrograms of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S-only vaccine. Studies in non-responders to S-only vaccines will be necessary to define an immunological advantage of the pre-S vaccines, and additional assessments will be necessary to determine whether anti-pre-S2 enhances protective efficacy.
乙肝病毒前S基因加S基因的产物在小鼠体内似乎比单独的S基因产物（乙肝表面抗原）更具免疫原性。因此，我们检测了一种含前S2加S的“中蛋白”基因产物的乙肝疫苗（前S疫苗）在健康成年人中的免疫原性。我们比较了三剂前S疫苗与市售重组乙肝疫苗（重组酵母乙肝疫苗）的免疫原性；87名血清学阴性的成年人被随机分为三组，分别于0、1和6个月时通过三角肌注射接种12微克（第1组）、24微克（第2组）或48微克（第3组）的前S疫苗，或10微克的重组酵母乙肝疫苗（第4组）。加强免疫后，≥94%的接种者出现了乙肝表面抗原抗体（抗-HBs）。免疫原性在接种48微克前S疫苗和重组酵母乙肝疫苗的受试者中最佳，仅在48微克前S疫苗剂量组（第3组）中，前S疫苗的几何平均滴度（GMT）高于重组酵母乙肝疫苗。75%的前S2疫苗接种者在7个月内产生了前S2抗体（重组酵母乙肝疫苗接种者未产生）。这些发现表明，前S疫苗在健康成年人中具有免疫原性，但需要48微克的当前制剂剂量才能达到或超过目前可用的仅含重组S疫苗的免疫原性。有必要对仅接种S疫苗无反应者进行研究，以确定前S疫苗的免疫学优势，还需要进行额外评估以确定抗前S2是否能增强保护效果。
