Chimeric dengue virus E glycoproteins comprising mutant domain I and domain II hinge regions
AssigneesThe University of North Carolina at Chapel Hill, Vanderbilt University
InventorsAravinda M. de Silva, A. Ruklanthi de Alwis, Wahala M. P. B. Wahala, Ralph S. Baric, William B. Messer, James E. Crowe, Jr., Scott A. Smith
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Abstract
The present invention provides compositions and methods of use comprising a chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone, which comprises amino acid substitutions that introduce a dengue virus E glycoprotein domain I and domain II hinge region from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.
Claims12
A chimeric dengue virus E glycoprotein selected from the group consisting of:
- a) a first dengue virus E glycoprotein backbone from dengue virus serotype 1 (SEQ ID NO:18) comprising a V50A substitution, an N52Q substitution, a P53L substitution, a V55T substitution, a K124P substitution, an L1251 substitution, an I129V substitution, an E202K substitution, a K203N substitution, a T275G substitution, and a T277S substitution;
- b) a second dengue virus E glycoprotein backbone from dengue virus serotype 2 (SEQ ID NO:20) comprising a K51T substitution, a Q52N substitution, a P222S, an M272T substitution, an S274G substitution, a G275T substitution, an N276T substitution, an L277T substitution;
- c) a third dengue virus E glycoprotein backbone from dengue virus serotype 2 (SEQ ID NO:20) comprising a K51T substitution, a P53L substitution, a Y59L substitution, an N124P substitution, an M1251 substitution, a P132Y substitution, an E202K substitution, an M272N substitution, an N276T substitution, an L277S substitution, and an L278I substitution;
- d) a fourth dengue virus E glycoprotein backbone from dengue virus serotype 3 (SEQ ID NO:17) comprising an A50V substitution, a Q52N substitution, an L53P substitution, a T55V substitution, a P124K substitution, an I125L substitution, a V1291 substitution, a K200E substitution, an N201K substitution, a G273T substitution, and an S275T substitution;
- e) a fifth dengue virus E glycoprotein backbone from dengue virus serotype 4 (SEQ ID NO:19) comprising a T49E substitution, an A50V substitution, a K51T substitution, an E52N substitution, a V53P substitution, an S272T substitution, a G273S substitution, a D274G substitution, a G275T substitution, an N276T substitution, an H277T substitution, and an M278I substitution;
- and
- f) a sixth dengue virus E glycoprotein backbone from dengue virus serotype 4 (SEQ ID NO:19) comprising a T49E substitution, a K51T substitution, an E52Q substitution, a V53L substitution, an L55T substitution, a T58K substitution, a Y59L substitution, a K124P substitution, a T126E substitution, an N128K substitution, an L129V substitution, an I132Y substitution, a K203N substitution, an N276T substitution, an H277S substitution, and an M278I substitution.
Dependencies are inferred from the claim text.