O'Neal C M, Clements J D, Estes M K, Conner M E
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Virol. 1998 Apr;72(4):3390-3. doi: 10.1128/JVI.72.4.3390-3393.1998.
We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 microg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavirus challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, effective mucosal adjuvant such as LT-R192G will increase the practicality of administering recombinant vaccines mucosally.
我们已证明，由蛋白VP2和VP6组成的轮状病毒2/6病毒样颗粒（2/6-VLPs）与霍乱毒素（CT）经鼻内给予小鼠后，可诱导其免受轮状病毒攻击，这通过病毒排泄来衡量。由于尚不清楚CT是否会被批准用于人类，我们评估了大肠杆菌不耐热毒素（LT）和LT-R192G的佐剂活性。将小鼠经鼻内接种10微克与CT、LT或LT-R192G联合的2/6-VLPs。所有三种佐剂诱导的轮状病毒特异性血清抗体和肠道免疫球蛋白G（IgG）的几何平均滴度相当。接种含LT的2/6-VLPs的小鼠产生的肠道IgA滴度显著高于以CT作为佐剂的小鼠。所有接种与LT和LT-R192G混合的2/6-VLPs的小鼠均完全（100%）受到保护，免受轮状病毒攻击，而接种与CT混合的2/6-VLPs的小鼠平均有91%受到保护，免受攻击。像LT-R192G这样安全、有效的黏膜佐剂的可用性将增加经黏膜给予重组疫苗的实用性。
