Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka.
MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Curr Opin Infect Dis. 2024 Oct 1;37(5):349-356. doi: 10.1097/QCO.0000000000001040. Epub 2024 Jul 24.
With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease.
The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability. However, there also appear to be significant differences in the kinetics of viraemia and nonstructural protein 1 (NS1) antigenemia and pathogenicity between different serotypes and genotypes of the DENV. These differences may have significant implications for development of treatments and in inducing robust immunity through dengue vaccines. Although generally higher levels of neutralizing antibodies are thought to protect against infection and severe disease, there have been exceptions and the specificity, breadth and functionality of the antibody responses are likely to be important.
Although there have been many advances in our understanding of dengue pathogenesis, viral and host factors associated with occurrence of severe dengue, vascular leak and the immune correlates of protection remain poorly understood.
目的综述：随着全球登革热发病率的显著上升，开发耐受性良好且有效的疫苗和疗法变得越来越重要。在这里，我们讨论了对导致重症登革热的免疫机制的最新认识，以及从过去的经验中可以吸取的教训，这些经验教训可以帮助我们找到治疗靶点、预后标志物和预防重症疾病的疫苗。
最近的发现：病毒血症的程度和持续时间似乎与临床疾病的严重程度有关，但也存在一些可变性。然而，不同血清型和基因型的登革热病毒在病毒血症和非结构蛋白 1（NS1）抗原血症的动力学以及致病性方面似乎也存在显著差异。这些差异可能对治疗方法的发展以及通过登革热疫苗诱导强大的免疫具有重要意义。尽管通常认为更高水平的中和抗体可以预防感染和重症疾病，但也有例外，抗体反应的特异性、广度和功能可能很重要。
总结：尽管我们对登革热发病机制、与重症登革热、血管渗漏和保护免疫相关的病毒和宿主因素有了很多了解，但仍有许多方面尚不清楚。
