Adams Ben, Boots Michael
Department of Animal and Plant Science, University of Sheffield, Sheffield S10 2TN, UK.
J Theor Biol. 2006 Sep 21;242(2):337-46. doi: 10.1016/j.jtbi.2006.03.002. Epub 2006 Apr 24.
When antibodies raised in response to a particular pathogen bind with immunologically similar pathogens it may facilitate infection through a phenomenon known as antibody-dependent enhancement (ADE). This process occurs between the four serotypes of dengue virus and, furthermore, secondary infection is a major risk factor in dengue hemorrhagic fever (DHF). Theory has suggested that ADE may be responsible for the large immunological distance between dengue serotypes. We investigate this hypothesis using an epidemic model for dengue in which immunological distance and the strength of immune cross-reaction are expressed separately. Cross-enhancement is considered in three alternative forms acting on susceptibility, transmission and mortality. Previous models have shown that transmission and mortality enhancement can lead to periodicity or chaos. We confirm this result for reasonable levels of susceptibility and transmission enhancement but not for mortality enhancement. We also show that when the two strains have identical basic reproductive numbers no form of enhancement leads to competitive exclusion. When the two strains have different basic reproductive numbers susceptibility or transmission enhancement allow strains with greater immunological similarity to stably coexist but mortality enhancement forces strains to be more distinct. All three forms of enhancement can be associated with DHF and we conclude that mortality enhancement must be dominant if ADE really is responsible for the immunological distance between dengue serotypes.
当针对特定病原体产生的抗体与免疫相似的病原体结合时，可能会通过一种称为抗体依赖增强（ADE）的现象促进感染。这个过程发生在登革热病毒的四种血清型之间，此外，二次感染是登革出血热（DHF）的主要风险因素。理论表明，ADE可能是造成登革热血清型之间较大免疫距离的原因。我们使用一个登革热流行模型来研究这个假设，在该模型中，免疫距离和免疫交叉反应强度被分别表示。交叉增强以作用于易感性、传播和死亡率的三种替代形式来考虑。先前的模型表明，传播和死亡率增强可导致周期性或混沌。我们在合理的易感性和传播增强水平下证实了这一结果，但在死亡率增强方面未得到证实。我们还表明，当两种毒株具有相同的基本繁殖数时，任何形式的增强都不会导致竞争排斥。当两种毒株具有不同的基本繁殖数时，易感性或传播增强允许免疫相似性更高的毒株稳定共存，但死亡率增强迫使毒株更加不同。所有三种增强形式都可能与登革出血热有关，我们得出结论，如果ADE真的是造成登革热血清型之间免疫距离的原因，那么死亡率增强必定占主导地位。
