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 the amino acid sequence:
(SEQ ID NO: 3)
MRCVGIGNRDFVEGLSGATWVDVVLEHGSCVTTMAKDKPTLDIELLKTEA
TQLATLRKLCIEAKISNTTTDSRCPTQGEATLVEEQDTNFVCRRTFVDRG
WGNGCGLFGKGSLITCAKFKCVTK I EGK V VQYENLKYSVIVTVHTGDQHQ
VGNETTEHGT I ATITPQAPTSEIQLTDYGALTLDCSPRTGLDFNEM I LLT
M KN K A W M VHRQWFLDLPLPWTSGASTSQETWNRQDLLVTFKTAHAKKQEV
VVLGSQEGAMHTALTGATEIQ N SG G T S IFAGHLKCRLKMKLTLKGMSYVM
CTGSFKLEKEVAETQHGTVLVQVKYEGTDAPCKIPFSSQDEKGVTQNGRL
ITANPIVTDKEKPVNIEAEPPFGESYIVVGAGEKALKLSWFKKG.
2. A chimeric dengue virus E glycoprotein, comprising the amino acid sequence:
(SEQ ID NO: 4)
MRCVGIGNRDFVEGLSGATWVDVVLEHGGCVTTMAKNKPTLDIEL F KTE V
T NP AVLRKLCIEGKITNITTDSRCPTQGEAVLPEEQDQNYVCKHTYVDRG
WGNGCGLFGKGSLVTCAKFQCLEPIEGKVVQYENLKY S VI V TVHTGDQHQ
VGNET TEH G TI A T ITPQA P TSE IQ LT D YG A LGLECSPRTGLDFNEMILLT
MKNKAWMVHRQWFFDLPLPWTSGATTETPTWNRKELLVTFKNAHAKKQEV
VVLGSQEGAMHTALTGATEIQ T SG T T T IFAGHLKCRLKMDKLELKGMSYA
MCTNTFVLKKEVSETQHGTILIKVEYKGEDAPCKIPFSTEDGQGKAHNGR
LITANPVVTKKEEPVNIEAEPPFGESNIVIGIGDNALKINWYKKG.
3. A flavivirus particle or virus like particle (VLP) comprising the E glycoprotein of claim 1 .
4. A composition comprising the E glycoprotein of claim 1 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 E glycoprotein of claim 1 .
6. A flavivirus particle or virus like particle (VLP) comprising the E glycoprotein of claim 2 .
7. A composition comprising the E glycoprotein of claim 2 in a pharmaceutically acceptable carrier.
8. A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the E glycoprotein of claim 2 .