A Shuttle Plasmid, Recombinant MVA/HIV1 Clinical Vaccine Constructs and a Mechanism for Enhanced Stability of Foreign Gene Inserts by Codon Alternation and for Insertion of the Foreign Gene Between Two Vaccinia Virus Essential Genes

Since the onset of the AIDS epidemic more than two decades ago, enormous efforts have been directed to making a vaccine that will protect against human immunodeficiency virus-1 (HIV); an effective vaccine is thought to require the induction of cellular and humoral responses. Vaccine candidates have included a variety of HIV immunogens delivered as DNA, attenuated poxviruses, adenoviruses, vesicular stomatitis virus, proteins, and various combinations thereof. The inventors' efforts to design an HIV vaccine have focused on modified vaccinia virus Ankara (MVA) as a vector.

Use of Mono-Amine Oxidase Inhibitors to Prevent Herpes Virus Infections and Reactivation from Latency

Available for licensing are methods of using Monoamine Oxidase Inhibitors (MAOIs) to prevent alpha-herpesvirus lytic infections, such as those caused by Herpes simplex virus (HSV-1 or HSV-2) and Varicella zoster virus (VZV), and to possibly prevent the periodic reactivation of these viruses from latency. MAOIs have been historically used to treat depression, hypertension, and related diseases. The invention describes how MAOIs can also inhibit LSD1, a histone/protein demethylase that is required for initiation of alpha-herpesvirus lytic infection.

Recombinant Vaccines Based on Poxvirus Vectors

The technology offered for licensing is foundational in the area of recombinant DNA vaccines. In the last several years, facilitated through a licensing program of the NIH, the technology has been broadly applied in the development and commercialization of several novel human and veterinary vaccines in the areas of infectious disease as well as cancer therapeutics. The NIH wishes to expand its licensing program of the subject technology in a variety of applications that will benefit public health.

Biological/Research Material for H1N1 Influenza Virus Vaccine Research

Offered for licensing is a recombinant attenuated vaccinia virus, MVA, that expresses the haemagglutinin (HA) and nucleoprotein (NP) of influenza virus A/PR/8/34 (H1N1). The virus has been shown to stimulate protective immunity to influenza virus in mice.

The materials can be used for research purposes and in particular in the area of influenza virus vaccines.

The related publications listed below demonstrate the usefulness of this biological material in influenza virus vaccine research.

Methods to Increase Stability of Recombinant Vaccinia-Vectored Vaccines and Increase Expression of a Foreign Gene Inserted in Such Vaccines

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.

Prevention and Treatment of Herpes Virus Infection by Inhibition of the JMJD2 Family of Histone Demethylases

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.

Prevention or Treatment of Viral Infections by Inhibition of the Histone Methyltransferases EZH1/2

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.