Mouse IL-12p40 Expressing Cell Line

The subject invention is a recombinant human 293T cell line that expresses mouse IL-12p40 protein to high levels. IL-12p40 is a subunit of both Interleukin-12 (IL-12) and IL-23; however, it can also be expressed as a monomer (IL-12p40) and as a homodimer (IL-12p80). IL-12p40 is produced mainly by antigen presenting cells such as macrophages, neutrophils, microglia, and dendritic cells in response to pathogens or inflammatory agents. It is an immunostimulatory messenger molecule that can disseminate in the body and signal the presence of a pathogen.

Mouse Model for Cerebral Cavernous Malformation, an Inherited Brain Disorder

Cerebral Cavernous Malformation (CCM) is a brain disease affecting up to 0.5% of the worldwide population. CCM is characterized by grossly dilated vessels prone to leaking and hemorrhage which result in severe headaches, seizures, and strokes. Inherited forms of the disease are due to mutations in one of three loci, CCM1, CCM2, and CCM3. Prior efforts to develop mice with targeted null mutations in Ccm1, Ccm2, or Ccm3 have been unsuccessful, as such mutations result in embryonic death.

Multivalent Vaccines for Rabies Virus and Filoviruses

No vaccine candidates against Ebola virus (EBOV) or Marburg virus (MARV) are nearing licensure and the need to develop a safe and efficacious vaccine against filoviruses continues. Whereas several preclinical vaccine candidates against EBOV or MARV exist, their further development is a major challenge based on safety concerns, pre-existing vector immunity, and issues such as manufacturing, dosage, and marketability. The inventors have developed a new platform based on live or chemically inactivated (killed) rabies virus (RABV) virions containing EBOV glycoprotein (GP) in their envelope.

Monoclonal Antibodies Against Poliovirus

Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.

Humanized Monoclonal Antibodies Efficient for Neutralization of Tick-Borne Encephalitis Virus (TBEV)

TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae.

Diagnostic Assays and Methods of Use for Detection of Filarial Infection

The effort targeting the mosquito borne neglected tropical disease lymphatic filariasis for elimination through mass drug administration by 2020 will require accurate, cost effective methods for detecting early infections. The World Health Organization-recommended immunochromatographic test detects adult Wuchereria bancrofti (Wb) antigen in blood, but shows variable efficacy due to the complex life cycle of the parasites and cross reactivity with other organisms. This variability may hinder effective lymphatic filariasis elimination efforts.

Protease Deficient Bacillus anthracis with Improved Recombinant Protein Yield Capabilities

Species of Bacillus, such as Bacillus anthracis, Bacillus cereus, and Bacillus subtilis, are attractive microorganisms for recombinant protein production in view of their fast growth rate, high yield, and ability to secrete produced products directly into the medium. Bacillus anthracis is also attractive in view of its ability to produce anthrax toxin and ability to fold proteins correctly. This application claims a B. anthracis strain in which more than one secreted protease is inactivated by genetic modification.

Broadly Neutralizing Human Anti-HIV Monoclonal Antibody 10E8 and Related Antibodies Capable of Neutralizing Most HIV-1 Strains

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.

Salen-Manganese Compounds for Therapy of Viral Infections

Salen-manganese compounds are synthetic, stable, low toxicity, low cost agents that may provide protection from immune reaction-related oxidative cell damage associated with many illnesses. In particular, oxidative cell damage has been associated with many viral infections including influenza. This invention demonstrates that treating mice with salen-manganese compounds, after lethal pandemic influenza virus infection, significantly enhances survival. Salen-manganese treatment also reduces lung pathology and also improved cellular recovery and repair.

Self-Assembled Ferritin Nanoparticles Expressing Hemagglutinin as an Influenza Vaccine

NIH inventors at the Vaccine Research Center have developed a novel influenza virus hemagglutinin (HA)-ferritin nanoparticle influenza vaccine that is easily manufactured, potent, and elicits broadly neutralizing influenza antibodies against multiple strains of influenza. This novel influenza nanoparticle vaccine elicited two types of broadly neutralizing, cross-protective antibodies, one directed to the highly conserved HA stem and a second proximal to the conserved receptor binding site (RBS) of the viral HA, providing a new platform for universal and seasonal influenza.