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New insights into the immunopathology and control of dengue virus infection
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New insights into the immunopathology and control of dengue virus infection
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Journal Article
New insights into the immunopathology and control of dengue virus infection
2015
Overview
Key Points
Dengue virus has four distinct serotypes, and infection with one serotype results in the development of homotypic immunity. Subsequent infection with a different serotype is associated with an increased risk of developing severe disease, leading to the suggestion that severe disease is triggered by immunopathology.
Both T cell- and B cell-mediated adaptive immune responses are thought to be involved in the immunopathology of severe dengue. Antibody-dependent enhancement and a skewed T cell response through original antigenic sin may have a role in disease pathogenesis in secondary infections.
There are several vaccine candidates in development; the most advanced in clinical trials is the Sanofi Pasteur vaccine CYD-TDV. A recent 3 year follow-up study demonstrated an overall vaccine efficacy of 65%, with lower efficacies and higher hospitalizations in children younger than 9 years old.
A large number of dengue virus-specific monoclonal antibodies have recently been described, and antibodies targeting envelope (E) protein domain III are among the most potently neutralizing but are often serotype-specific. Recently, however, a broadly neutralizing antibody directed against the E protein dimer epitope (EDE) has been discovered.
Antibodies directed against precursor membrane (prM) protein can facilitate Fc receptor-mediated uptake of immature viral particles, which, although non-infectious in the absence of antibody, can undergo prM cleavage following endocytosis in the host cell, rendering them infectious.
Future vaccines need to target potently neutralizing epitopes, such as those found on E protein domain III, or the quaternary epitopes, such as EDE, and minimize poorly neutralizing and potentially disease-enhancing prM or FLE antibodies.
This Review describes the role of the immune system in dengue pathogenesis. The authors also discuss new insights gained from human monoclonal antibodies against dengue virus as well as the recent vaccine trials and the challenges to develop an effective dengue vaccine.
Dengue virus poses a major threat to global public health: two-thirds of the world's population is now at risk from infection by this mosquito-borne virus. Dengue virus causes a range of diseases with a small proportion of infected patients developing severe plasma leakage that leads to dengue shock syndrome, organ impairment and bleeding. Infection with one of the four viral serotypes results in the development of homotypic immunity to that serotype. However, subsequent infection with a different serotype is associated with an increased risk of developing severe disease, which has led to the suggestion that severe disease is triggered by immunopathology. This Review outlines recent advances in the understanding of immunopathology, vaccine development and human monoclonal antibodies produced against dengue virus.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - therapeutic use
/ Dengue
/ Dengue - prevention & control
/ Dengue Vaccines - immunology
/ Dengue Vaccines - therapeutic use
/ Dengue Virus - growth & development
/ Epitopes
/ Host-Pathogen Interactions - drug effects
/ Host-Pathogen Interactions - immunology
/ Humans
/ Immune response (cell-mediated)
/ Life Cycle Stages - immunology
/ Proteins
/ Vaccines
/ Viruses
