USA As Represented by Secretary of the Navy

US Government As Represented by the Secretary of the Army

Monika Simmons

Kevin R Porter

Joseph R Putnak

Wellington Sun

Curtis G Hayes

Raviprkash Kanakatte

Sun Wellington

The invention relates to a method for preventing, ameliorating or treating disease caused by dengue virus in a subject in need thereof comprising administering to the subject a dengue vaccine formulation in combination with a NS3 helicase polypeptide and/or fragment(s) thereof, wherein said method comprises stimulating humoral as well as cell-mediated immunity to the dengue virus in the subject.

Immune enhancing recombinant dengue protein

The invention relates to methods for the induction of an immune response to dengue virus. The method of inducing an immune response against dengue virus comprises administration of a non-replicating immunogen followed by a boost with a tetravalent live attenuated viral vaccine. Another aspect of the inventive subject matter is a method of inducing an immune response against dengue virus using a heterologous prime-boost regimen with the priming immunogen comprising a DNA expression system, an adenovirus expression vector or a Venezuelan equine encephalitis virus replicon system and the boosting immunogen comprising the same without the DNA expression system. Each expression system contains DNA sequences encoding dengue viral proteins.

Induction of an immune response against dengue virus using the prime-boost approach

A recombinant fusion protein (DEN-2 MBP) containing the B domain of the due (DEN 2 envelope protein is disclosed as a candidate subunit immunogen for vaccination against dengue virus infection. A gene fragment encoding amino acid 298 to amino acid 400 of the DEN-2 virus envelope was expressed as a fusion protein with the maltose binding protein (MBP) of Escherichia coli (E. coli). The recombinant fusion protein was purified and analyzed for its antigenicity imunogenicity and ability to protect mice against lethal challenge. This antigen is detected by monoclonal antibody (3H5) which is specific for a neutralizing epitope on the DEN-2 envelope and reacted with homologous polyclonal mouse immune ascitic fluid and DEN-2 immune human sera. A recombinant fusion plasmid bearing the DEN-2 MBP DNA sequence, expressing the fusion product in E. coli is disclosed. The fusion protein when administered to a host elicits a virus neutralizing antibody response which confers partial protection to the recipient animals against challenge infection. Sera from immunized mice revealed no neutralizing antibodies to any of the other DEN serotypes in the plaque reduction neutralization assay (PRNT).

Recombinant dengue virus envelope protein/maltose-binding protein

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Germantown, MD, United States of America

Monika Simmons