Methods and compositions for dengue virus vaccines
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 an epitope that is recognized by an antibody from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.
1. A chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone that comprises the following amino acid substitutions that introduce an epitope that is recognized by an antibody that is reactive with a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone; wherein the amino acid residue numbering is based on the reference amino acid sequence of an E glycoprotein of dengue virus serotype 3 (DENV3) identified as SEQ ID NO:1: T138S, Q158H, V160T, S169P, A173I, I174Q, P176T, E177D, N272T, G275T, and S277T, and wherein said dengue virus E glycoprotein further comprises an insertion of the amino acid residues T and E between amino acid residues 155 and 156.
2. A flavivirus particle or virus like particle (VLP) comprising the chimeric dengue virus E glycoprotein of claim 1 .
3. A composition comprising the chimeric dengue virus E glycoprotein of claim 1 in a pharmaceutically acceptable carrier.
4. A composition comprising the flavivirus particle or VLP of claim 2 in a pharmaceutically acceptable carrier.
5. A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of claim 1 .
6. A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the flavivirus particle or VLP of claim 2 .