US Government As Represented by the Secretary of the Army

U.S. Army Medical Research Institute of Infectious Diseases Department of the Army

Alan L Schmaljohn

Peter M Pushko

Jonathan F Smith

Michael C Hevey

Connie S Schmaljohn

Jay Hooper

Mary Kate Hart

Julie A Wilson

Diane L Negley

Sina Bavari

Kelly Lyn Warfield

Case C Grogan

M Javad Aman

Dana Swenson

Diane I Negley

Chimeric GP molecules were constructed which contain portions of both the EBOV and MBGV GP proteins by swapping the subunits between EBOV and MBGV. The chimeric molecules were cloned into an alphavirus replicon which offers the advantage of high protein expression levels in mammalian cells and is a proven vaccine vector. These chimeric molecules fully protected guinea pigs from MBGV challenge, and conversely protected the animals from EBOV challenge. These results indicate that a protective epitope resides within the GP2 subunit of the MBGV GP protein and at least partially within the GP2 subunit of the EBOV GP protein. Additionally these results show that a construction of a single-component bivalent vaccine protective in guinea pigs is achievable.

Chimeric filovirus glycoprotein

In this application are described filovirus-like particles for both Ebola and Marburg and their use as a diagnostic and therapeutic agent as well as a filovirus vaccine. Also described is the association of Ebola and Marburg with lipid rafts during assembly and budding, and the requirement of functional rafts for entry of filoviruses into cells.

Generation of virus-like particles and use as panfilovirus vaccine

Using the MBGV GP, NP, and virion proteins, a method and composition for use in inducing an immune response which is protective against infection with MBGV in nonhuman primates is described.

Methods for producing Marburg virus proteins

Venezuelan equine encephalitis virus replicon encoding marburg virus proteins

Using the Ebola GP, NP, VP24, VP30, VP35 and VP40 virion proteins, a method and composition for use in inducing an immune response which is protective against infection with Ebola virus is described.

Ebola virion proteins expressed from venezuelan equine encephalitis (VEE) virus replicons

In this application are described Ebola GP monoclonal antibodies and epitopes recognized by these monoclonal antibodies. Also provided are mixtures of antibodies of the present invention, as well as methods of using individual antibodies or mixtures thereof for the detection, prevention, and/or therapeutical treatment of Ebola virus infections in vitro and in vivo.

Monoclonal antibodies to Ebola glycoprotein

In this application are described vaccinia monoclonal antibodies. Also provided are mixtures of antibodies of the present invention, as well as methods of using individual antibodies or mixtures thereof for the detection, prevention, and/or therapeutical treatment of vaccinia virus infections in vitro and in vivo.

Prophylactic and therapeutic monoclonal antibodies

In this application is described a poxvirus naked DNA vaccine which protects animals against poxvirus challenge comprising IMV and EEV nucleic acids from poxvirus. Methods of use of the vaccine and its advantages are described.

DNA vaccines against poxviruses

The invention here relates to recombinant DNA constructs which comprise a Venezuelan equine encephalitis replicon vector and at least one DNA fragment encoding a protective antigen from the Marburg virus. The DNA constructs are useful for inducing an immune response which is protective against infection with Marburg virus in nonhuman primates.

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Frederick, MD, United States of America

Alan L Schmaljohn