Department of Epidemiology, Harvard School of Public Health, Center for Communicable Disease Dynamics, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15504-9. doi: 10.1073/pnas.1102445108. Epub 2011 Aug 29.
Many highly diverse pathogen populations appear to exist stably as discrete antigenic types despite evidence of genetic exchange. It has been shown that this may arise as a consequence of immune selection on pathogen populations, causing them to segregate permanently into discrete nonoverlapping subsets of antigenic variants to minimize competition for available hosts. However, discrete antigenic strain structure tends to break down under conditions where there are unequal numbers of allelic variants at each locus. Here, we show that the inclusion of stochastic processes can lead to the stable recovery of discrete strain structure through loss of certain alleles. This explains how pathogen populations may continue to behave as independently transmitted strains despite inevitable asymmetries in allelic diversity of major antigens. We present evidence for this type of structuring across global meningococcal isolates in three diverse antigens that are currently being developed as vaccine components.
尽管存在遗传交换的证据,但许多高度多样化的病原体种群似乎仍稳定地存在于离散的抗原类型中。已经表明,这可能是由于对病原体种群的免疫选择而产生的,导致它们永久地分成离散的、不重叠的抗原变体亚群,以最大限度地减少对可用宿主的竞争。然而,在每个基因座的等位变体数量不相等的情况下,离散的抗原菌株结构往往会瓦解。在这里,我们表明,随机过程的纳入可以通过某些等位基因的丢失,导致离散菌株结构的稳定恢复。这解释了为什么尽管主要抗原的等位基因多样性不可避免地存在不对称,但病原体种群仍可能继续表现为独立传播的菌株。我们提出了证据表明,这种结构在三种不同的抗原中存在于全球脑膜炎球菌分离株中,这些抗原目前正在被开发为疫苗成分。