McNeal M M, Broome R L, Ward R L
Division of Clinical Virology, J. N. Gamble Institute of Medical Research, Cincinnati, Ohio 45219.
Virology. 1994 Nov 1;204(2):642-50. doi: 10.1006/viro.1994.1579.
Using an adult mouse model to study active immunity against rotavirus infection, it was previously shown that oral immunization with some, but not all, animal rotavirus strains induced protection against subsequent infection following oral challenge with the murine rotavirus strain EDIM. To determine if a specific rotavirus protein could be associated with protection in this model, mice were immunized with a series of 18 reassortants between the fully protective EDIM strain and a partially protective heterologous rotavirus strain (RRV-G). Reassortants that contained genes for EDIM proteins responsible for protection were anticipated to provide complete protection; however, no EDIM proteins were found to be both necessary and sufficient for full protection. Instead, protection was found to be highly correlated with viral shedding (P = 0.005) and with serum rotavirus IgA titers stimulated by the different reassortants (P < 0.001). This indicated that protection was related to the intestinal replication properties of the different reassortants rather than to specific immunogenic properties of EDIM proteins. This conclusion was supported by the finding that the titers of serum rotavirus IgA, but not IgG, stimulated in mice following oral immunization with a series of animal rotaviruses was directly related to protection against EDIM. If these findings can be extended to humans, they suggest that the efficiency of intestinal replication following oral inoculation with a live rotavirus vaccine candidate may be the primary determinant of successful immunization.
利用成年小鼠模型研究针对轮状病毒感染的主动免疫，先前的研究表明，用部分而非全部动物轮状病毒株进行口服免疫可诱导小鼠在经鼠轮状病毒株EDIM口服攻击后获得对后续感染的保护。为了确定在该模型中是否有特定的轮状病毒蛋白与保护作用相关，用完全具有保护作用的EDIM株和部分具有保护作用的异源轮状病毒株（RRV-G）之间的18个重配株对小鼠进行免疫。预期含有负责保护作用的EDIM蛋白基因的重配株能提供完全保护；然而，未发现有任何EDIM蛋白对完全保护既是必需的也是充分的。相反，发现保护作用与病毒排泄高度相关（P = 0.005），也与不同重配株刺激产生的血清轮状病毒IgA滴度高度相关（P < 0.001）。这表明保护作用与不同重配株在肠道中的复制特性有关，而不是与EDIM蛋白的特定免疫原性有关。这一结论得到以下发现的支持：用一系列动物轮状病毒对小鼠进行口服免疫后刺激产生的血清轮状病毒IgA而非IgG的滴度与对EDIM的保护作用直接相关。如果这些发现能够推广到人类，那么这表明口服接种活的轮状病毒候选疫苗后在肠道中的复制效率可能是成功免疫的主要决定因素。
