Dengue viruses cluster antigenically but not as discrete serotypes

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Science  18 Sep 2015:
Vol. 349, Issue 6254, pp. 1338-1343
DOI: 10.1126/science.aac5017

The devil in the dengue details

Along with their mosquito vectors, dengue viruses are spreading worldwide to infect millions of people. For a few, subsequent infection results in lethal hemorrhagic disease. Katzelnick et al. used antibody-binding data to map structural divergence and antigenic variation among dengue viruses. Comparing results in monkeys and humans, the viruses approximately clustered into the four known groups. However, the four virus groups showed as much antigenic distance within a group as between groups. This finding helps explain why immune responses to dengue are highly variable, and it has complex implications for epidemiology, disease, and vaccine deployment.

Science, this issue p. 1338


The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.

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