Whitehead Institute for Biomedical Research

Children's Medical Center Corporation

The Beth Israel Hospital Association

Beth Israel Hospital

Anna Aldovini

Richard A Young

David Baltimore

Didier Trono

Michael A O'Donnell

Mark B Feinberg

William C DeWolf

Rosemary B Duda

The present invention pertains to mutated, non-infectious HIV viral particles, vectors for production of such particles and vaccines employing such vectors. The non-infectious particles are obtained by introducing a number of inactivating mutations into a native viral genome. These mutations are designed so as to minimize the probability of genetic reversion to an infectious virus, while retaining the basic protein content and immunogenic properties of a wild-type virion. The altered viral genome expresses proteins that can assemble into non-infectious particles which contain immunogenic components of the virus, but which are unable to infect cells. The preferred mutations are introduced in at least one amino acid position of the nucleocapsid (NC) protein in combination with at least one other mutation in an amino acid position of the reverse transcriptase (RT) protein or the In protein. In one embodiment, the mutations to the native HIV genome may also be made in at least one amino acid position of the NC protein, at least one position in the RT protein, and at least one position in the integrase (In) protein. In another embodiment, the mutations to the native HIV genome may be introduced in clusters, where two or more mutations are made in the NC protein, the RT protein, the In protein, or any combinations thereof.

DNA vectors containing mutated HIV proviruses

A method of transforming slow-growing mycobacteria, such as BCG, and ; a method of manipulating genomic DNA of slow-growing mycobacteria through homologous recombination; a method of producing homologously recombinant (HR) slow-growing mycobacteria in which heterologous DNA is integrated into the genomic DNA at a homologous locus; homologously recombinant (HR) slow-growing mycobacteria having heterologous DNA integrated into their genomic DNA at a homologous locus; and mycobacterial DNA useful as a genetic marker.

Homologously recombinant slow growing mycobacteria and uses therefor

A method of transforming slow-growing mycobacteria, such as M. bovis BCG, M. leprae, M. tuberculosis M. avium, M. intracellulare and M. africanum; a method of manipulating genomic DNA of slow-growing mycobacteria through homologous recombination; a method of producing homologously recombinant (HR) slow-growing mycobacteria in which heterologous DNA is integrated into the genomic DNA at a homologous locus; homologously recombinant (HR) slow-growing mycobacteria having heterologous DNA integrated into their genomic DNA at a homologous locus; and mycobacterial DNA useful as a genetic marker.

This invention related to constructs comprising mutant HIV genomes having an alteration in a nucleotide sequence which is critical for genomic RNA packaging and non-infectious, immunogenic HIV particles produced by expression of these constructs in mammalian cells. Cell lines which stably produce non-infectious, immunogenic HIV particles are also included. Prophylactic and therapeutic vaccines, diagnostic reagents, and related methods are further described.

Non-infectious HIV particles and uses therefor

The present invention relates to recombinant mycobacteria, particularly recombinant M. bovis BCG, which express heterologous DNA encoding a product (protein or polypeptide) of interest, such a protein or polypeptide (e.g., an antigen) against which an immune response is desired, or a cytokine.

Recombinant mycobacterial vaccines

The present invention relates to recombinant mycobacteria, particularly recombinant M. bovis BCG, which express heterologous DNA encoding a product (protein or polypeptide) of interest, such a protein or polypeptide (e.g., an antigen) against which an immune response is desired or a cytokine.

Growing community of inventors

Winchester, MA, United States of America

Anna Aldovini