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This invention claims Modified Vaccinia Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing Human Immunodeficiency Virus (HIV) env, gag, and pol genes, where the genes are isolated from Ugandan Clade D isolates, Kenyan Clade A isolates, and Tanzanian Clade C isolates. In a rhesus macaque SHIV model, DNA priming followed by a recombinant MVA (rMVA) booster controlled a highly pathogenic immunodeficiency challenge. Both the DNA and the rMVA components of the vaccine expressed multiple immunodeficiency virus proteins.

The technology offered for licensing is in the field of vaccinia-based recombinant vaccines. In particular the invention relates to methods of stabilizing the recombinant virus, thus resulting in efficient production of the vaccine and efficient expression of the inserted gene. Stabilization of the recombinant virus is achieved by the insertion of the exogenous gene into an intergenic region (IGR) of the viral genome (i.e. Modified Vaccinia Ankara, MVA), where the IGR is flanked by open reading frames of conserved poxvirus genes.

One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells.

Investigators at the NIH have discovered a potential means for preventing or treating a herpes virus infection by inhibiting the activity of the host cell’s histone demethylases. When herpesviruses enter a cell, they are inactivated by cellular defense mechanisms that wrap the viral genome in repressive chromatin structures. In order for viral replication to progress, the host’s own histone demethylases are recruited to the viral genome to reverse this repression.

The present invention is related to a recombinant viral vector for vaccines.

Currently available poxvirus vectors for humans and other animals exhibit suboptimal expression of recombinant gene(s) and high expression of vector proteins which causes weak immunogenicity and high anti-vector immune response.

Herpes simplex viral infections, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), are exceptionally common worldwide. These viruses establish lifelong persistent infections with cycles of lytic reactivation to produce recurrent diseases including oral and genital lesions, herpetic keratitis/blindness, congenital-developmental syndromes, and viral encephalitis. Infection with HSV-2 increases the rate of human immunodeficiency virus (HIV) transmission in coinfected individuals. DNA replication inhibitors are typically used to treat herpesvirus infections.

Mutation in gene A34R can regulate the release of progeny virions from the surface of parental cells.

This invention involves the use of inhibitors of alpha-4 beta-7 (a4b7) integrin to inhibit HIV transmission/infection, as a prophylactic to inhibit onset of the acute stage of HIV infection or to treat HIV infection. The a4b7 integrin inhibitors were previously developed for use in other diseases, such as multiple sclerosis or inflammatory bowel disease.

The uses for human anti-HIV monoclonal antibody 10E8 and its variants include passive immunization, therapeutic vaccination, and the development of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing antibodies isolated and it neutralizes up to 98% of diverse HIV-1 strains. 10E8 is specific to the membrane-proximal external region (MPER) of the HIV envelope protein gp41 and 10E8 is orthogonal to other anti-HIV antibodies. In combination with other antibodies 10E8 may provide an antibody response that neutralizes nearly all strains of HIV-1.