Protection by Immunoglobulin Dual-Affinity Retargeting Antibodies against Dengue Virus

Dengue virus (DENV) is a mosquito-transmitted, enveloped, positive-sense RNA virus and member of theFlavivirus genus of the Flaviviridae family. Infection by four closely related but serologically distinct viruses (DENV serotype 1 [DENV-1], DENV-2, DENV-3, and DENV-4) causes dengue fever (DF), an acute self-limiting yet severe febrile illness, or dengue hemorrhagic fever and shock syndrome (DHF/DSS), a potentially fatal vascular leakage syndrome. While primary infection is believed to confer long-term immunity against strains of the homologous DENV serotype, epidemiological studies suggest that secondary infection with a heterologous DENV serotype can enhance the risk of DHF/DSS due to preexisting and nonneutralizing, cross-reactive antibodies (1, 2) and/or T cells (3–5). A requirement for protection against all four serotypes has limited the development of vaccines and antibody-based therapies against DENV.