Green K Y, Kapikian A Z
Epidemiology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Virol. 1992 Jan;66(1):548-53. doi: 10.1128/JVI.66.1.548-553.1992.
Sera from 17 of 18 adult volunteers challenged with a virulent serotype 1 rotavirus strain (D) were examined for prechallenge antibody levels against several well-defined rotavirus VP7 and VP4 neutralization epitopes by a competitive epitope-blocking immunoassay (EBA) in order to determine whether correlates of resistance to diarrheal illness could be identified. The presence of prechallenge serum antibody at a titer of greater than or equal to 1:20 that blocked the binding of a serotype 1 VP7-specific monoclonal antibody (designated 2C9) that maps to amino acid residue 94 in antigenic site A on the serotype 1 VP7 was significantly associated with resistance to illness or shedding (P less than 0.001) or illness and shedding (P less than 0.01) following challenge with the serotype 1 virus. In addition, an EBA antibody titer of greater than or equal to 1:20 in prechallenge serum against a serotype 3 VP7-specific epitope (defined by monoclonal antibody 954/159) that maps to amino acid 94 on the serotype 3 VP7 was also significantly associated with resistance to illness or shedding (P = 0.02), with a trend for protection against illness and shedding. A trend was also noted between the presence of EBA antibody against a cross-reactive VP4 epitope common to many human rotavirus strains, including the challenge virus, or a rhesus monkey rotavirus strain-specific VP4 antigenic site, and resistance to illness or shedding. These data confirm that the presence of serum antibody correlates with resistance to rotavirus illness or shedding but, in addition, demonstrate the association of antibody to a specific epitope with resistance to illness or shedding. These data also suggest that antigenic site A on the rotavirus VP7, composed of amino acids 87 to 96, may be involved in the formation of a major protective epitope. Further study of the role of this epitope in the development of homotypic and heterotypic immunity to rotaviruses following natural or vaccine-induced infection may be important in the development of strategies for control of rotavirus diarrheal disease.
为了确定是否能够找到与抵抗腹泻疾病相关的因素，我们通过竞争性表位阻断免疫分析法（EBA），检测了18名接受强毒株1型轮状病毒株（D）攻击的成年志愿者中17人的血清，以检测其针对几种明确的轮状病毒VP7和VP4中和表位的攻击前抗体水平。攻击前血清抗体滴度大于或等于1:20，且能阻断1型VP7特异性单克隆抗体（命名为2C9）的结合，该单克隆抗体对应于1型VP7抗原位点A中的氨基酸残基94，这与感染1型病毒后抵抗疾病或病毒排出（P<0.001）或抵抗疾病和病毒排出（P<0.01）显著相关。此外，攻击前血清中针对3型VP7特异性表位（由单克隆抗体954/159确定）的EBA抗体滴度大于或等于1:20，该表位对应于3型VP7上的氨基酸94，这也与抵抗疾病或病毒排出显著相关（P = 0.02），有预防疾病和病毒排出的趋势。针对许多人类轮状病毒株（包括攻击病毒）共有的交叉反应性VP4表位或恒河猴轮状病毒株特异性VP4抗原位点的EBA抗体的存在与抵抗疾病或病毒排出之间也存在一种趋势。这些数据证实血清抗体的存在与抵抗轮状病毒疾病或病毒排出相关，但此外，还证明了针对特定表位的抗体与抵抗疾病或病毒排出之间的关联。这些数据还表明，由氨基酸87至96组成的轮状病毒VP7上的抗原位点A可能参与主要保护性表位的形成。进一步研究该表位在自然感染或疫苗诱导感染后轮状病毒同型和异型免疫发展中的作用，对于制定控制轮状病毒腹泻疾病的策略可能很重要。
