Modelling the relationship between antibody-dependent enhancement and immunological distance with application to dengue
Modelling the relationship between antibody-dependent enhancement and immunological distance with application to dengue
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DOI：
10.1016/j.jtbi.2006.03.002
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发表时间：
2006-09-21
影响因子：
2
通讯作者：
Boots, Michael
中科院分区：
文献类型：
--
作者：
Adams, Ben;Boots, Michael
当针对特定病原体产生的抗体与免疫学上相似的病原体结合时，它可能通过称为抗体依赖性增强（ADE）的现象促进感染。这一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的主要危险因素。理论表明，ADE可能是登革热血清型之间较大免疫距离的原因。我们研究了这一假设，使用登革热的流行病模型，其中免疫距离和免疫交叉反应的强度分别表示。交叉增强被认为是在三个替代形式的易感性，传播和死亡率。以前的模型已经表明，传播和死亡率的提高可能导致周期性或混沌。我们证实了这一结果的合理水平的易感性和传输增强，但不是死亡率增加。我们还表明，当两个菌株具有相同的基本繁殖数没有任何形式的增强导致竞争排斥。当两个菌株具有不同的基本繁殖数时，易感性或传播增强允许具有更大免疫相似性的菌株稳定共存，但死亡率增强迫使菌株更加不同。所有这三种形式的增强都与登革出血热有关，我们得出结论，如果ADE真的是登革热血清型之间免疫距离的原因，那么死亡率的增强一定是占主导地位的。(c)2006爱思唯尔有限公司保留所有权利。
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. (c) 2006 Elsevier Ltd. All rights reserved.