Towards a broadly active flavivirus therapeutic antibody
Author:
Throsby Mark
de Kruif John
Publisher:
Future Medicine
ISSN:
1746-0794
Source:
Future Virology,
Vol.4,
Iss.5, 2009-09,
pp. : 419-422
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Abstract
Evaluation of: Sultana H, Foellmer HG, Neelakanta G et al.: Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody. J. Immunol. 183(1), 650–660 (2009). Flaviviruses, such as West Nile virus, the dengue serotypes, Japanese encephalitis virus and yellow fever virus are important human pathogens and can co-circulate in parts of the world. Humoral immunity is important in the mammalian protective response to flaviviruses and passive immunization has been shown to be effective in preventing infection and even treating disease. Monoclonal antibodies (mAbs) against flaviviruses can be divided basically into potent neutralizing mAbs with restricted flavivirus cross-reactivity and broadly cross-reactive mAbs with low neutralizing potency and protective activity. Here, Sultana and colleagues extend the characterization of the cross-reactive mAb11 by defining its epitope within the fusion loop of the West Nile virus envelope protein and link the reduced neuroinvasiveness of a mAb11 neutralization escape variant to a diminished ability to activate Toll-like receptor 3, induce inflammatory cytokine release and compromise blood–brain barrier integrity. The results highlight the importance of the fusion loop in viral pathogenesis; however, challenges remain to develop mAb11 into a viable therapeutic. Instead, mixtures of potent neutralizing mAbs with different flavivirus specificities may be a more feasible approach toward a broadly active flavivirus therapeutic antibody product.