Abstract
Laurent Coudeville, Jean Lang, and Remy Teyssou are employees of Sanofi-Pasteur (France). Adrienne Guignard, Gerhart Knerer, and Baudoin Standaert are employees of GSK Biologicals (Belgium). Joachim Hombach and Pem Namgyal are staff members of the World Health Organization. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the World Health Organization. All other authors have declared that no competing interests exist. This work was primarily funded by the World Health Organization, and funded in part by the Gates Foundation's Vaccine Modeling Initiative, the Dengue Vaccine to Vaccination Initiative (v2V), and the Pediatric Dengue Vaccine Initiative (PDVI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Highlights
Dengue viruses are single-stranded positive-sense RNA viruses that are the etiological agents of dengue fever (DF)
In line with the theory behind antibody-dependent enhancement (ADE), subneutralizing antibody concentrations—theoretically occurring when immunity is waning or between vaccine doses—represent a potential risk of severe dengue to patients infected with wild-type virus during this critical period
This individual-level risk can be evaluated with sufficient follow-up, but population-level effects cannot be analyzed in the context of a vaccine trial
Summary
Dengue viruses are single-stranded positive-sense RNA viruses (genus Flavivirus, family Flaviviridae) that are the etiological agents of dengue fever (DF). 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 line with the theory behind ADE, subneutralizing antibody concentrations—theoretically occurring when immunity is waning or between vaccine doses—represent a potential risk of severe dengue to patients infected with wild-type virus during this critical period This individual-level risk can be evaluated with sufficient follow-up, but population-level effects cannot be analyzed in the context of a vaccine trial. As these facets of dengue biology are further investigated, we will gain confidence that future mathematical models may come close to an accurate representation of true dengue epidemics
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