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Human antibody blocks dengue virus in mice

July 02, 2015

Researchers have discovered that a human antibody specific to dengue virus serotype 2, called 2D22, protects mice from a lethal form of the virus -- and they suggest that the site where 2D22 binds to the virus could represent a potential vaccine target. The mosquito-borne virus, which infects nearly 400 million people around the world each year, has four distinct serotypes, or variations, and there is currently no protective vaccine available. Recent phase 3 clinical trials of a potential vaccine candidate showed poor efficacy, especially against dengue virus serotype 2. Guntur Fibriansah and colleagues found that 2D22 protects mice against dengue virus serotype 2, regardless of whether it's administered before or after the rodents are inoculated with the virus. This finding suggests that the antibody may act as both a preventative and a therapeutic agent. To learn more, the researchers analyzed cryo-electron microscopy (cryo-EM) structures of 2D22 in complex with two different strains of viral serotype 2 -- the dengue serotype with the most dynamic surface -- at 6.5 and 7.0 angstroms. These cryo-EM structures reveal that 2D22 binds to viral envelope proteins, locking about two-thirds of them in place on the viral surface and preventing them from reorganizing into the orientations required to enter host cells.
Article #19: "Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers," by G. Fibriansah; T.-S. Ng; J.L. Tan; X.-N. Lim; J.S.G. Ooi; V.A. Kostyuchenko; J. Wang; S.-M. Lok at Duke-National University of Singapore Graduate Medical School in Singapore; G. Fibriansah; T.-S. Ng; J.L. Tan; X.-N. Lim; J.S.G. Ooi; V.A. Kostyuchenko; J. Wang; S.-M. Lok at National University of Singapore in Singapore; K.D. Ibarra; E. Harris at University of California, Berkeley in Berkeley, CA; S.A. Smith; J.E. Crowe Jr. at Vanderbilt University in Nashville, TN; A.M. de Silva at University of North Carolina School of Medicine in Chapel Hill, NC.

American Association for the Advancement of Science

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