自身抗体的竞争性排斥可阻止广泛中和HIV-1抗体的产生。
Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising.
作者信息
Luo Shishi, Perelson Alan S
机构信息
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545; Center for Nonlinear Systems, Los Alamos National Laboratory, Los Alamos, NM 87545.
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545;
出版信息
Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11654-9. doi: 10.1073/pnas.1505207112. Epub 2015 Aug 31.
The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. If less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.
在过去十年中，人们发现了许多针对1型人类免疫缺陷病毒（HIV-1）的广谱且强效的单克隆抗体。通过疫苗接种来引发这些抗体似乎非常困难，这主要是因为它们在感染后期才出现，并且相对于种系抗体序列发生了高度突变。在此，我们使用一个计算模型表明，广谱抗体实际上可能更早出现且突变较少，但由于自体抗体反应的竞争性排斥，它们可能无法如此。我们进一步发现，在由多种不同毒株引发的感染中，这种竞争性排斥较弱，广谱中和抗体出现的时间比由单一毒株引发的感染更早。我们的计算模型模拟了共同进化的多类型病毒和抗体群体。因此，适应性免疫系统产生广谱中和抗体可能比之前认为的更容易。如果存在突变较少的广谱抗体，那么使用包含多种不同病毒株混合物的疫苗来引发它们或许是可行的。
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