Dna vectors containing mutated hiv proviruses

Abstract

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.