Dengue Fever: Theories of Immunopathogenesis and Challenges for Vaccination

Abstract

Dengue fever is a mosquito-borne viral disease infecting several hundred million people in tropical and subtropical areas every year. Its clinical manifestations range from mild fever to severe life-threatening shock syndrom. No therapeutics or licensed vaccines are available yet and with half of the world's population already at risk, it represents a major public health concern. The co-existence of four different Dengue virus serotypes renders difficult the obtaining of full protective immunity against each one of them. On the contrary, these serotypes trigger significant cross-reactivities of antibodies and T cells, both of which may lead to disease enhancement when reactivated in the context of reinfection with a heterologous serotype. Several immunological concepts have been developed to explain disease enhancement, and the uncertainty around the topic has consequently slowed down the development of Dengue vaccines. Recent advances however have shed light on key aspects of both the immunoprotective and immunopathological mechanisms. In particular the responses of specific antibodies and T cells have been a focus of many studies. These immunological players are thought to directly influence a cytokine dysbalance that eventually leads to severe disease and vascular leakage. In this review I outline current concepts and ongoing debates on the above topics. A better understanding of Dengue virus immunopathogenesis is critically needed to optimize candidate vaccines including those currently under development. In particular, the results from large-scale human efficacy trials will offer outstanding opportunities to refine correlates of protection and design even more effective vaccines.

A Retrospective Analysis of the Significance of Haemoglobin SS and SC in Disease Outcome in Patients With Sickle Cell Disease and Dengue Fever

“…The higher mortality in sickle cell disease compared to the general population may be due to heighten inflammatory response in sickle cell disease relative to subjects without sickle cell disease. For example recent advances have shown that specific antibodies and T cells directly influence a cytokine imbalance in dengue that eventually leads to severe disease and vascular damage ( Remy, 2014 ). Additionally, several studies in patients with SCD have shown excessive inflammatory cytokines in both steady-state and during a vaso-occlusive crisis and therefore the existence of ongoing inflammation ( Musa et al, 2010 ).…”

Skin eruptions in children: Drug hypersensitivity vs viral exanthema

“…The high affinity of BL with viral antigens can be considered a putative triggering mechanism for DIE. Specifically, viral infections could be a co‐factor for activating drug specific T cells, which would otherwise undergo apoptosis, and a long‐lasting DHR would not be developed 24 …”

Secondary dengue infection in immunocompetent murine model leads to heart tissue damage

“…However, immunity against the heterologous serotypes is transient (Sabin, 1952). As a consequence, secondary infection may lead to severer manifestations of DEN due to cross-reactivity of non-neutralizing antibodies and/or proliferation of lowaffinity T-cells (Mathew and Rothman, 2008;Duangchinda Secondary dengue infection in immunocompetent murine model leads to heart tissue damage Remmy, 2014). Currently, there is no available treatment for DEN and the only way to prevent infection is avoiding the bite of Aedes mosquitoes in endemic areas (CDC, 2012).…”