Neutralizing Antibodies to Influenza HA and Their Use and Identification

The effectiveness of current influenza vaccines varies by strain and season, in part because influenza viruses continuously evolve to evade human immune responses. While the majority of seasonal influenza infections cause relatively mild symptoms, each year influenza virus infections result in over 500,000 hospitalizations in the United States and Europe. Current standard of care for individuals hospitalized with uncomplicated influenza infection is administration of neuraminidase inhibitors.

Stabilized Group 2 Influenza Hemagglutinin Stem Region Trimers and Uses Thereof

Researchers at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID) have designed influenza vaccine candidates based on group 2 influenza hemagglutinin (HA) proteins. These group 2 HA proteins were engineered to remove the highly variable head region and stabilize the remaining stem region. The researchers then fused the engineered group 2 HA stabilized stem with a ferritin subunit. The resulting fusion protein can self-assemble into nanoparticles which display group 2 HA stem domain trimers on their surface.

Novel Multivalent Nanoparticle Vaccines

Current seasonal influenza vaccines are designed to elicit immunity to circulating strains of influenza each year. The targeted strains are selected based on predictions of which strains are likely to be predominant in the human population for a given year. This prediction must be made well ahead of the influenza season to allow time for vaccine production and can be inaccurate.

Chimeric SHIV Gag Proteins Optimize T-Cell Response Against HIV Gag

HIV Gag has been included in nearly all HIV vaccines entering clinical trials because of its importance in SIV models and its correlation with protection in HIV-infected long-term non-progressors. However, HIV Gag has proven less immunogenic than Env in phase I clinical trial studies. Through sequence comparison, two regions in HIV Gag have been identified as contributing to the decreased immunogenicity observed for HIV Gag. Replacement of these regions with corresponding SIV sequences significantly increased the resulting T-cell response to HIV Gag in mice.

Increased Protein Expression Vector for Vaccine Applications

An expression vector with a unique promoter that results in higher level of protein expression than vectors currently in use is available for licensing from the NIH. The elevated levels of expression are achieved through use of a specific promoter, known as CMV/R, in which the Human T-Lymphotrophic Virus (HTLV-1) Long Terminal Repeat (LTR) R-U5 region is substituted for a portion of the intron downstream of the CMV immediate early region 1 enhancer (Barouch et al., 2005). Sequences of 95% or better homology to CMV/R can be used as well.

Full-Length cDNA Clone Representing the Consensus Sequence of the RNA Genome of a Human Norovirus (strain MD145-12) That Encodes Biologically Active Proteins

The invention provides for a full-length cloned cDNA copy of the RNA genome of a predominant norovirus strain (Genogroup II.4) designated MD145-12 that was associated with human gastrointestinal illness. The noroviruses, which were formerly known as "Norwalk-like" viruses are estimated to cause 23 million cases of acute gastroenteritis in the USA each year. The virus has been designated into category B of the CDC biodefense-related priority pathogens because it can be used as an agent of bioterrorism.

The Use of Rabbits with Defined Immunoglobulin Light Chain Genes (C<sub>kappa</sub> b allotypes) to Optimize Production of Chimeric and Humanized Monoclonal Antibodies for Therapeutic, Imaging and Diagnostic Applications

Biological materials are important research tools that can be used for diagnostic as well as therapeutic purposes. Antibodies have become viable drugs in the market today and there is a general market need for systems that may facilitate production of efficient and effective antibodies. In recent years, monoclonal antibodies have gained significant importance in their use, both as diagnostics and therapeutics, to intervene and combat diseases such as cancer, cardiovascular diseases, and infections.

Human lgA Monoclonal Antibody that Targets a Conserved Site on the Plasmodium Falciparum Circumsporozoite Protein

Scientists at NIAID have isolated MAD2-6, an IgA antibody active against Plasmodium falciparum sporozoites, the infectious agent of malaria. In 2019, the majority of the 229 million cases resulted from P. falciparum infections. Because P. falciparum has a complex lifecycle during human infection, most advanced malaria vaccine candidates and current chemoprophylaxis drugs can confer only partial, short-term protection in malaria-endemic areas. Thus, the MAD2-6 antibody could be used alone or in combination with current technology.

SARS-CoV-2 Iinfection of Human Lung Epithelial Cells Triggers a Cell-Mediated Acute Fibrin Fibrosis

Scientists at NIAID have developed a method of treatment for virus-induced lung fibrosis using nebulized thrombin inhibitors. Since March 2020, the WHO estimates that 564 million people have been infected with SARS-CoV-2 world-wide. Lung fibrosis is a major factor associated with SARS-CoV-2 infections and can contribute to mortality. Additionally, severe SARS-CoV-2 cases can result in long-term pulmonary disease due to lung fibrosis. At present, attempts to treat lung fibrosis developed during a SARS-CoV-2 infection using intravenous heparin have been unsuccessful.