Assessing the potential of a candidate dengue vaccine with mathematical modeling

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Gomes, M. Gabriela M., WHO-VMI Dengue Vaccine Modeling Group (2012) Assessing the potential of a candidate dengue vaccine with mathematical modeling. PLOS Neglected Tropical Diseases, 6 (3). e1450. ISSN 1935-2727 (https://doi.org/10.1371/journal.pntd.0001450)

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Abstract

Dengue viruses are single-stranded positive-sense RNA viruses (genus Flavivirus, family Flaviviridae) that are the etiological agents of dengue fever (DF). More than 2 billion people live in dengue-endemic areas, and dengue virus infections account for an estimated 500,000 episodes of severe disease each year. A recent review suggests that these may be underestimates. Despite the fact that the virus has been expanding in geographic range over the past four decades, there are still no licensed drugs or vaccines and no consistently effective vector interventions to combat dengue. DF is caused by four antigenically distinct viral serotypes. Each type gives rise to both life-long serotype-specific immunity and short-term cross-protective immunity against the other serotypes thought to last between 2 and 9 months. The spectrum of disease ranges from asymptomatic infection to life threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The most distinctive feature of dengue's clinical/epidemiological profile is the increased risk of severe disease following infection by a heterologous dengue serotype in an immunologically primed individual. During this secondary infection, a complex interaction is triggered between the host's immune system and the infecting virus. In this setting, elevated risk of severe dengue has been attributed to the circulation of sub-neutralizing concentrations of heterologous anti-dengue virus antibody creating an effect known as antibody-dependent enhancement (ADE) of infection and greater viral burden in vivo. In turn, this leads to a host immune response that is suggested to precipitate increased capillary permeability, cardiovascular shock, and hemorrhage characteristic of clinically severe dengue. Viral and other host factors may also contribute to pathogenicity. To accurately assess the effects of dengue vaccine candidates on individuals and populations, these pathophysiological mechanisms of severe dengue must be understood.

ORCID iDs

Gomes, M. Gabriela M. ORCID logoORCID: https://orcid.org/0000-0002-1454-4979;
CORE (COnnecting REpositories)