Protective immunity to vaccinia virus induced by vaccination with multiple recombinant outer membrane proteins of intracellular and extracellular virions
Protective immunity to vaccinia virus induced by vaccination with multiple recombinant outer membrane proteins of intracellular and extracellular virions
复制标题
DOI：
10.1128/jvi.78.19.10230-10237.2004
复制
发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Moss, B
中科院分区：
文献类型：
--
作者：
Fogg, C;Lustig, S;Moss, B
传染性细胞内和细胞外形式的牛痘病毒具有不同的外膜蛋白，向免疫系统呈现多个目标。我们研究了可溶形式的 L1（胞内成熟病毒的外膜蛋白）以及 A33 和 B5（胞外有包膜病毒的外膜蛋白）的免疫原性。将 10 杯量的重组蛋白与 Ribi 或皂苷型佐剂混合，皮下给予小鼠。在第一次和第二次加强后，每种蛋白质的抗体滴度急剧上升，达到超过活痘苗病毒经皮免疫诱导的水平。蛋白质免疫后免疫球蛋白 G1 (IgG1) 抗体占主导地位，表明辅助性 T 细胞 2 型反应，而活牛痘病毒主要诱导 IgG2a，表明辅助性 T 细胞 I 型反应。用任何一种重组蛋白免疫的小鼠都能在5倍于50%致死剂量的痘苗病毒WR毒株的鼻内攻击中存活下来。体重减轻的测量表明 A33 免疫接种最有效地预防疾病。当攻击病毒剂量增加20倍时，蛋白质组合的优越性得到了证明。通过结合细胞内和细胞外病毒外膜的重组蛋白制成的疫苗获得了最好的保护。事实上，用 A33 加 B5 加 L1 或用 A33 加 L1 免疫的小鼠比用活痘苗病毒免疫的小鼠得到更好的保护。使用三蛋白组合进行三次免疫对于完全保护是必要且充分的。这些研究表明多蛋白天花疫苗的可行性。
Infectious intracellular and extracellular forms of vaccinia virus have different outer membrane proteins, presenting multiple targets to the immune system. We investigated the immunogenicity of soluble forms of L1, an outer membrane protein of the intracellular mature virus, and of A33 and B5, outer membrane proteins of the extracellular enveloped virus. The recombinant proteins, in 10-mug amounts mixed with a Ribi- or saponin-type adjuvant, were administered subcutaneously to mice. Antibody titers to each protein rose sharply after the first and second boosts, reaching levels that surpassed those induced by percutaneous immunization with live vaccinia virus. Immunoglobulin G1 (IgG1) antibody predominated after the protein immunizations, indicative of a T-helper cell type 2 response, whereas live vaccinia virus induced mainly IgG2a, indicative of a T-helper cell type I response. Mice immunized with any one of the recombinant proteins survived an intranasal challenge with 5 times the 50% lethal dose of the pathogenic WR strain of vaccinia virus. Measurements of weight loss indicated that the A33 immunization most effectively prevented disease. The superiority of protein combinations was demonstrated when the challenge virus dose was increased 20-fold. The best protection was obtained with a vaccine made by combining recombinant proteins of the outer membranes of intracellular and extracellular virus. Indeed, mice immunized with A33 plus B5 plus L1 or with A33 plus L1 were better protected than mice immunized with live vaccinia virus. Three immunizations with the three-protein combination were necessary and sufficient for complete protection. These studies suggest the feasibility of a multiprotein smallpox vaccine.