Merck Sharp + Dohme Corp.

Beth-Ann Griswold Coller

Andrew J Bett

D Elliot Parks

Ramesh V Chintala

Vidya B Pai, Jr

Michele Yelmene

Govindarajan Dhanasekaran

Timothy Martyak

Danilo R Casimiro

The present invention relates to dengue virus vaccine compositions comprising a first and a second dengue vaccine, wherein the first dengue vaccine comprises at least one live, 5 attenuated dengue virus or live, attenuated chimeric dengue virus and the second dengue vaccine is a recombinant dengue subunit vaccine, a DNA vaccine, a conjugate vaccine, or an inactivated dengue vaccine; wherein the genome of the live attenuated dengue virus or the live attenuated chimeric dengue virus comprises a 30 nucleotide deletion of the TL2 stem-loop structure of the 3' untranslated region. The dengue virus vaccine compositions of the invention may further 10 comprise one or more adjuvants. In preferred embodiments of the invention, the first and the second dengue vaccine are tetravalent. The invention also relates to methods of using the dengue virus vaccine compositions of the invention to treat or prevent dengue infection, or to prevent, ameliorate, or delay the onset or progression of the clinical manifestations thereof.

Dengue virus vaccine compositions and methods of use thereof

The present invention provides dengue virus vaccines and immunogenic compositions for administration to human subjects. The vaccine compositions of the present invention comprise recombinantly produced monomeric and/or dimeric forms of truncated dengue virus envelope glycoprotein that, when formulated together with an adjuvant and a pharmaceutically acceptable carrier, induce balanced tetravalent immune responses. In preferred embodiments of the compositions described herein, the DEN4 protein component is a dimeric form of DEN4. The compositions are designed to be acceptable for use in the general population, including immunosuppressed, immunocompromised, and immunosenescent individuals. Also provided herein are methods of inducing a protective immune response in a human patient population by administering the compositions described herein to the patients.

Recombinant subunit dengue virus vaccine

The present invention relates to dengue virus vaccine compositions comprising a first and a second dengue vaccine, wherein the first dengue vaccine is a live, attenuated dengue vaccine and the second dengue vaccine is a recombinant dengue subunit vaccine or an inactivated dengue vaccine; wherein the live attenuated dengue vaccine comprises at least one live, attenuated dengue virus or at least one live attenuated chimeric flavivirus. The dengue virus vaccine compositions of the invention may further comprise one or more adjuvants. In preferred embodiments of the invention, the first and the second dengue vaccine are tetravalent. The invention also relates to methods of using the dengue virus vaccine compositions of the invention to treat or prevent dengue infection, or to prevent, ameliorate, or delay the onset or progression of the clinical manifestations thereof.

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Kaneohe, HI, United States of America

Beth-Ann Griswold Coller