National Institutes of Health, a Component of the US Dept. of Health & Human Services

Ching-Juh Lai

Stephen Whitehead

Brian R Murphy

Joseph E Blaney

Kathryn A Hanley

Robert H Purcell

Lewis Markoff

Barry Falgout

Robert M Chanock

Alexander G Pletnev

Ruhe Men

Ana P Goncalvez

Kenneth H Eckels

Michael Bray

Yi-Ming Zhang

Stephen S Whitehead

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3' untranslated region (3′-UTR) comprising a Δ30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR that removes sequence in the 5′ direction as far as the 5′ boundary of the TL-3 homologous structure in each of the dengue serotypes 1, 2, 3, and 4, or a replacement of the 3′-UTR of a dengue virus of a first serotype with the 3′-UTR of a dengue virus of a second serotype, optionally containing the Δ30 mutation and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

Development of dengue virus vaccine components

The invention relates to a dengue virus tetravalent vaccine containing a common 30 nucleotide deletion (&#x394;30) in the 3'-untranslated region of the genome of dengue virus serotypes 1, 2, 3, and 4, or antigenic chimeric dengue viruses of serotypes 1, 2, 3, and 4.

Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3'-UTR of dengue types 1,2,3, and 4, or antigenic chimeric dengue viruses 1,2,3, and 4

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3' untranslated region (3&#x2032;-UTR) comprising a &#x394;30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the &#x394;30 mutation deleted from the 3&#x2032;-UTR that removes sequence in the 5&#x2032; direction as far as the 5&#x2032; boundary of the TL-3 homologous structure in each of the dengue serotypes 1, 2, 3, and 4, or a replacement of the 3&#x2032;-UTR of a dengue virus of a first serotype with the 3&#x2032;-UTR of a dengue virus of a second serotype, optionally containing the &#x394;30 mutation and nucleotides additional to the &#x394;30 mutation deleted from the 3&#x2032;-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.

Attenuated mutant dengue viruses comprising a mutation in the NS5 non-structural protein

Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3'-utr of dengue types 1, 2, 3, and 4, or antigenic chimeric dengue viruses 1, 2, 3, and 4

Development of mutations useful for attenuating dengue viruses and chimeric dengue viruses

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3' untranslated region (3&#x2032;-UTR) comprising a &#x394;30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the &#x394;30 mutation deleted from the 3&#x2032;-UTR that removes sequence in the 5&#x2032; direction as far as the 5&#x2032; boundary of the TL-3 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, or a replacement of the 3&#x2032;-UTR of a dengue virus of a first serotype with the 3&#x2032;-UTR of a dengue virus of a second serotype, optionally containing the &#x394;30 mutation and nucleotides additional to the &#x394;30 mutation deleted from the 3&#x2032;-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3'-UTR of dengue types 1, 2, 3, and 4, or antigenic chimeric dengue viruses 1, 2, 3, and 4

Disclosed herein are isolated humanized monoclonal antibodies that specifically bind Japanese encephalitis virus (JEV) with a binding affinity of about 1.0 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. Methods of treating, preventing, and/or ameliorating JEV infection in a subject with JEV also are disclosed. Additionally, the antibodies can be used to detect JEV in a sample, and methods of diagnosing JEV infection, or confirming a diagnosis of JEV infection in a subject, are disclosed herein that utilize these antibodies.

Humanized monoclonal antibodies that specifically bind and/or neutralize Japanese encephalitis virus (JEV) and their use

The invention features novel attenuated dengue virus mutants and compositions thereof. The invention further features an attenuated dengue virus comprising a proline to leucine change at amino acid position 2343 of non-structural protein 4B (NS4B), wherein the numbering is based upon the prototypic isolate DEN4 Dominica 1981 and the attenuated mutant DEN virus has at least one of the following properties: improved replication in Vero cells or restricted replication in mosquito cells.

Growing community of inventors

Bethesda, MD, United States of America

Ching-Juh Lai