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.
Claims24
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, a T51K substitution, an N52Q substitution, a V55T substitution, an L59Y substitution, a K124N substitution, an L125M substitution, an I129V substitution, a Y132P substitution, a K203N substitution, an S205A substitution, a K210R substitution, a T221L substitution, an S222P substitution, a T272M substitution, a G274S substitution, a T275G substitution, a T276N substitution, a T277L substitution, an I278L substitution, and an A280T substitution;
- b) a second 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 L125I substitution, an I129V substitution, an E202K substitution, a K203N substitution, an S205A substitution, a L207M substitution, a K210R substitution, a L2141F substitution, a T272N substitution, a T275G substitution, and a T277S substitution;
- and
- c) a third dengue virus E glycoprotein backbone from dengue virus serotype 1 (SEQ ID NO:18) comprising an E49T substitution, a V50A substitution, a T51K substitution, an N52E substitution, a P53V substitution, a V55L substitution, a K58T substitution, an L59Y substitution, an L125I substitution, an EL26T substitution, a K128N substitution, an I129L substitution, a Y132I substitution, an E202K substitution, an S205T substitution, an S222A substitution, a Q271D substitution, a T272S substitution, an S273G substitution, a G274D substitution, a T275G substitution, a T276N substitution, a T277H substitution, and an I278M substitution.
A chimeric dengue virus E glycoprotein selected from the group consisting of:
- a) a first dengue virus E glycoprotein backbone from dengue virus serotype 2 (SEQ ID NO:20) comprising an A50V substitution, a K51T substitution, a Q52N substitution, a T55V substitution, a Y59L substitution, an N124K substitution, an M125L substitution, a V129I substitution, a P132Y substitution, an N203K substitution, an A205S substitution, an R210K substitution, an L221T substitution, a P222S, an M272T substitution, an S274G substitution, a G275T substitution, an N276T substitution, an L277T substitution, an L278I substitution, and a T280A substitution;
- b) a second 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 M125I substitution, a P132Y substitution, an E202K substitution, an L207M substitution, an L214F substitution, an L221T substitution, a P222S substitution, an M272N substitution, an S274G substitution, an N276T substitution, an L277S substitution, an L278I substitution, and a I280A substitution;
- and
- c) a third dengue virus E glycoprotein backbone from dengue virus serotype 2 (SEQ ID NO:20) comprising an E49T substitution, a Q52E substitution, a P53V substitution, a T55L substitution, a K58T substitution, an N124K substitution, an M125I substitution, an E126T substitution, a K128N substitution, a V129L substitution, a P132I substitution, an E202K substitution, an N203K substitution, an A205T substitution, an R210K substitution, an L221T substitution, a P222A substitution, a Q271D substitution, an M272S substitution, an S273G substitution, an S274D substitution, an L277H substitution, an L278M substitution, and a T280A substitution.
A chimeric dengue virus E glycoprotein selected from the group consisting of:
- a) a first 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 V129I substitution, a K200E substitution, an N201K substitution, an A203S substitution, an M205L substitution, an R208K substitution, an F212L substitution, an N270T substitution, a G273T substitution, and an S275T substitution;
- b) a second dengue virus E glycoprotein backbone from dengue virus serotype 3 (SEQ ID NO:17) comprising a T51K substitution, an L53P substitution, an L59Y substitution, a P124N substitution, an 125M substitution, a Y132P substitution, a K200E substitution, an M205L substitution, an F212L substitution, a T219L substitution, an S220P substitution, an N270M substitution, a G272S substitution, a T274N substitution, an S275L substitution, an I276L substitution, and an A278T substitution;
- c) a third dengue virus E glycoprotein backbone from dengue virus serotype 3 (SEQ ID NO:17) comprising an E49T substitution, a T51K substitution, a Q52E substitution, an L53V substitution, a T55L substitution, a K58T substitution, an L59Y substitution, a P124K substitution, an E126T substitution, a K128N substitution, a V129L substitution, a Y132I substitution, an N201K substitution, an A203T substitution, an M205L substitution, an R208K substitution, an F212L substitution, an S220A substitution, a Q269D substitution, an N270S substitution, an S271G substitution, a G272D substitution, a T274N substitution, an S275H substitution, and an I276M substitution;
- and
- d) a fourth dengue virus E glycoprotein backbone from dengue virus serotype 3 (SEQ ID NO:17) comprising a T51K substitution, a Q52E substitution, an L53V substitution, a T55L substitution, a K58T substitution, an L59Y substitution, a P124K substitution, an E126T substitution, a K128N substitution, a V129I, substitution, a T198K substitution, N201K substitution, an A203T substitution, an M205L substitution, an R208K substitution, an F212L substitution, an S220A substitution, an I268V substitution, a Q269D substitution, an N270S substitution, an S271G substitution, a G272D substitution, a T274N substitution, an S275H substitution, and an 1276M substitution.
A chimeric dengue virus E glycoprotein selected from the group consisting of:
- a) a first 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 VS3P substitution, an L55V substitution, a T58K substitution, a Y59L substitution, an I125L substitution, a T126E substitution, an N128K substitution, an L129I substitution, an I132Y substitution, a K202E substitution, a T205S substitution, an A222S substitution, a D271Q substitution, an S272T substitution, a G273S substitution, a D274G substitution, a G275T substitution, an N276T substitution, an H277T substitution, and an M278I substitution;
- b) a second dengue virus E glycoprotein backbone from dengue virus serotype 4 (SEQ ID NO:
- 19) comprising a T49E substitution, an E52Q substitution, a V53P substitution, an L55T substitution, a T58K substitution, a K124N substitution, an I125M substitution, a T126E substitution, an N28K substitution, an L129V substitution, an I132P substitution, a K202E substitution, a K203N substitution, a T205A substitution, a K210R substitution, a T221L substitution, an A222P substitution, a D271Q substitution, an S272M substitution, a G273S substitution, a D274S substitution, an H277L substitution, an M278L substitution, and an A280T substitution;
- and
- c) a third 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, a T205A substitution, an I207M substitution, a K210R substitution, an L214F substitution, an A222S substitution, a D271Q substitution, an S272N substitution, a G273S substitution, a D274G substitution, an N276T substitution, an H277S substitution, and an M278I substitution.
Dependencies are inferred from the claim text.