MVA Expressing Modified HIV envelope, gag, and pol Genes

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.

Anti-Vaccinia Monoclonal Antibody

The current technology describes a monoclonal antibody that reacts with a vaccinia virus protein abundantly expressed under an early viral promoter after infection of cells. The antibody is useful for quantitating vaccinia virus infected cells and for studying the function of the protein to which it binds, which is known to be a double stranded RNA binding protein involved in resistance of the virus to interferons. This antibody is available for licensing through a biological materials license agreement.

Recombinant MVA Viruses Expressing Clade A/G and Clade B Modified HIV Env, Gag and Pol Genes Useful for HIV Vaccine Development

The current technology relates to the construction, characterization and immunogenicity of modified vaccinia Ankara (MVA) recombinant viruses. The MVA double recombinant viruses express modified/truncated HIV-1 Env and mutated HIV Gag Pol under the control of vaccinia virus early/late promoters. This technology describes the MVA double recombinant viruses made by homologous recombination of single MVA recombinants, one expressing Env and one expressing Gag Pol. These single MVA recombinants are made using a transiently expressed GFP marker that is deleted in the final viruses.

Transmission-Blocking Vaccine Against Malaria (1)

A transmission blocking vaccine developed against malaria contains a recombinant virus, which encodes a unique portion of the sexual stage surface antigen of Plasmodium falciparum (referred to as Pfs25), or the Pfs25 protein purified from infected host cells. Mice inoculated with the recombinant virus developed antibodies capable of blocking transmission of the virus. None of the monoclonal antibodies known to block transmission recognize the reduced Pfs25 antigen. This vaccine, which induces high, long-lasting titers at low cost, can be useful for controlling malaria.

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.

HIV Monoclonal Antibodies

This technology describes several hybridomas that produce monoclonal antibodies (mAbs) useful in HIV research applications. The mAbs are specific for either gp41 or gp120. In particular, the hybridomas producing mAbs designated D19, D56, M12, T8 and T24 (all anti-gp120), and T32 and T33 (gp41 specific) were found to be of particular utility. Additional hybridomas expressing mAbs disclosed in the publications may also be available.

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.