USA As Represented by Secretary of the Navy

Kevin R Porter

Monika Simmons

Tadeusz Kochel

Curtis G Hayes

Stephen L Hoffman

Wellington Sun

Ryan C Maves

Kanakatte Raviprakash

Raviprkash Kanakatte

A method to prepare inactivate viral vaccine by exposing the virus to a predetermined concentration of an inactivating psoralen, and a preselected intensity of ultraviolet radiation for a time period sufficiently long to render the virus non-infectious but less than that which would result in degradation of its antigenic characteristics.

Psoralen-inactivated viral vaccine and method of preparation

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 vaccine for promoting an immune response in a mammalian subject includes a eucaryotic plasmid expression vector which include at least part of the envelope gene and optionally, the PreM gene of dengue virus. In order to minimize immune enhancement, vaccines of up to the four serotypes of dengue are combined in a single vaccine. The vaccine in a suitable pharmaceutical carrier constitutes a pharmaceutical composition which is injected into the subject.

Dengue nucleic acid vaccines that induce neutralizing antibodies

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).

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Gaithersburg, MD, United States of America

Kevin R Porter