Thomas Jefferson University

The Wistar Institute

Bernhard Dietzschold

Douglas Craig Hooper

Hilary Koprowski

Matthias Johannes Schnell

Milosz Faber

Charles E Rupprecht

D Craig Hooper

Ellen Heber-Katz

Eric Wickstrom

Zhen Fang Fu

Marie Luise Faber

An immune response in a subject is elicited by a regiment comprising immunization with an attenuated recombinant rabies virus encoding at least one foreign protein antigen, and booster immunization with the at least one foreign protein antigen in a vehicle that does not contain adjuvant. The foreign protein antigen may comprise a prion protein antigen, a cancer-associated antigens, a viral antigen, a bacterial antigens, or a protozoal antigen. The prime/boost regimen produces predominantly IgG 2A/C and IgG 2B antibodies against the foreign protein antigen, indicating a TH1 response. Rabies virus attenuation may be provided, for example, by one or more mutations in the rabies glycoprotein gene which confers attenuation of pathogenicity.

Immunization with rabies virus vector expressing foreign protein antigen

The invention provides a recombinant rabies viruses comprising three copies of a mutated G gene wherein each G gene encodes a rabies virus glycoprotein having the amino acid 194 mutated to a serine and the amino acid 333 is mutated to a glutamic acid. The recombinant rabies virus is nonpathogenic in immunodeficient mammals and can be used in a vaccine to induce an immune response protect mammals from infection by rabies virus as well as clear a pre-existing rabies virus infection from neural tissues.

Attenuated live triple G protein recombinant rabies virus vaccine for pre- and post-exposure prophylaxis of rabies

Recombinant rabies viruses in which the arginine residue of the glycoprotein (G) at amino acid position 333 is exchanged, renders these viruses nonpathogenic for immunocompetent mammals regardless of the route of infection. Some of these recombinant rabies viruses after several serial virus passages in newborn mice can become pathogenic for adult mice. The reversion to the pathogenic phenotype is associated with a thymidine to adenosine mutation (T&#x2192;A) at position 639 of the G gene, which results in an asparagine to lysine exchange at position 194 of G. The codon at position 637-639 was changed by site directed mutagenesis to replace asparagine at position 194 by an amino acid that minimized the possibility for an Asn&#x2192;Lys exchange at amino acid position 194 of G and prevents reversion to a pathogenic form of the virus.

Recombinant rabies virus compositions

Live rabies virus vaccines comprising a recombinant rabies virus genome which overexpresses the rabies virus G protein increase apoptotic activity in infected cells, and enhance the generation of anti-rabies immunity in a subject.

Recombinant rabies vaccine and methods of preparation and use

Live, attenuated recombinant rabies virus vaccines are generated using reverse genetics to combine the antigenic determinants that render the rabies virus non-pathogenic with the determinants that are responsible for the elicitation of an effective anti-rabies immune response. These vaccines do not affect the antigenic, and therefore the immunogenic, properties of the virus. The present invention further relates to recombinant rabies virus vaccines that express a pro-apoptotic protein, such as cytochrome c, to increase the capacity to induce apoptosis, thereby enhancing the protective immunity against rabies. This new generation of live rabies virus vaccines represents a safe and effective approach to the eradication of rabies in wildlife, and subsequently humans and livestock.

Genetically engineered rabies recombinant vaccine for immunization of stray dogs and wildlife

Recombinant antibodies are disclosed. The nucleic acid and encoded amino acid sequences of the heavy and light chain immunoglobulins of human monoclonal rabies virus neutralizing antibodies, and their use, are described.

Recombinant antibodies, and compositions and methods for making and using the same

Human monoclonal rabies virus neutralizing antibodies represent a safe and efficacious post-exposure prophylactic therapy for individuals exposed to a rabies virus. The nucleic acid and encoded amino acid sequences of the heavy and light chain immunoglobulins of human monoclonal rabies virus neutralizing antibodies, and their use, is described.

Rabies virus-specific neutralizing human monoclonal antibodies and nucleic acids and related methods

Oligodeoxynucleotides complementary to genomic RNA of a negative-stranded nonsegmented RNA virus are provided. Methods of inhibiting infection of cells by a negative-stranded nonsegmented RNA virus and treating animals infected with a negative-stranded nonsegmented RNA virus using these oligodeoxynucleotides are also provided.

Antigenomic oligodeoxynucleotides for treatment of infection by negative-stranded nonsegmented RNA viruses

Methods of enhancing an antigen-induced immune response through use of a ribonucleocapsid complex are provided. Composition containing a ribonucleocapsid complex and an antigen which are capable of enhancing the immune response to the antigen are also provided.

Viral ribonucleocapsid as an immunological enhancer

A novel method of presenting an immunogenic peptide to an antigen presenting cell (APC) of a mammalian host, in order to generate a T cell response protective against a virus, such as herpes or rabies virus, comprising administering an immunologically effective amount of (1) a peptide-fatty acid conjugate, the peptide having the amino acid sequence corresponding to the sequence of a fragment of a glycoprotein or protein of the virus which produces a T cell response or a synthetic replica thereof, (2) a liposome composition and (3) an adjuvant so that the peptide protrudes from the liposome and when the liposome fuses with the APC, the peptide remains bound to the cell surface of the APC membrane.

Method for generating an immunogenic T cell response protective against

Pharmaceutical compositions that comprise a pharmaceutically acceptable carrier or diluent and a antibodies that each comprise at least a portion of the variable region from MAb 1112-1 are disclosed. Methods of treating individuals suspected of exposure to rabies are disclosed.

Growing community of inventors

Newtown Square, PA, United States of America

Bernhard Dietzschold