Korthals Altes Hester, de Boer Rob, Boerlijst Maarten
Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, PO Box 94084, 1090 GB Amsterdam, The Netherlands.
Proc Biol Sci. 2006 Jul 7;273(1594):1697-704. doi: 10.1098/rspb.2006.3511.
The great variability in the time between infection with HIV and the onset of AIDS has been the object of intense study. In the current work, we examine a mathematical model that focuses on the role of immune response variability between patients. We study the effect of variation in both the avidity and the breadth of the immune response on within-patient disease dynamics, viral setpoint and time to AIDS. We conclude that immune response variability can explain the observed variability in disease progression to a large extent. It turns out that the avidity, more than the breadth of the immune response, determines disease progression, and that the average avidity of the five best clones is a much better correlate for disease progression than the total number of clones responding. For the design of vaccines, this would suggest that, if given the choice between stimulating a broader, but average avidity response or a narrower high-avidity response, the latter option would yield better control of virus load and consequently slow down disease progression.
从感染艾滋病毒到艾滋病发作之间的时间存在巨大差异，这一直是深入研究的对象。在当前的研究中，我们考察了一个数学模型，该模型聚焦于患者之间免疫反应变异性的作用。我们研究了免疫反应亲和力和广度的变化对患者体内疾病动态、病毒载量及艾滋病发病时间的影响。我们得出结论，免疫反应变异性在很大程度上可以解释所观察到的疾病进展变异性。结果表明，决定疾病进展的是免疫反应的亲和力而非广度，并且与疾病进展的相关性而言，五个最佳克隆的平均亲和力比有反应的克隆总数要好得多。对于疫苗设计来说，这意味着，如果要在刺激更广泛但平均亲和力的反应和更狭窄的高亲和力反应之间做出选择，后一种选择将能更好地控制病毒载量，从而减缓疾病进展。
