This technology is directed towards a potential treatment for a new disease, CHAPLE (Complement Hyperactivation, Angiopathic thrombosis, and Protein-Losing Enteropathy), identified by NIAID researchers. CHAPLE is associated with GI symptoms and vascular thrombosis and is caused by loss-of-function variants in the gene encoding the complement regulatory protein CD55. The disease is caused by enhanced activation of the complement pathway and complement-mediated induction of intestinal lymphangiectasia and protein-losing enteropathy.

The VRC01-class of potent, broadly neutralizing antibodies (bnAbs) targets the conserved CD4-binding site (CD4bs) of HIV-1 Env which has been a major target of HIV-vaccine design. The current best priming immunogen to engage the VRC01-class germline precursors is the eOD-GT8 60mer, which elicits VRC01-class precursors in multiple transgenic mouse models. However, a large proportion of the antibodies elicited by eOD-GT8 60mer are non-CD4bs or “off-target” antibodies, undermining its effectiveness in eliciting the VRC01-class bnAb precursors.

Multiple sclerosis (MS) is an autoimmune disease caused by activated autoimmune T lymphocytes in patients resulting in inflammatory demyelination in the central nervous system. Current treatments are focused on functional control of these activated autoimmune T cells, but these treatments are non-specific T cell inhibitors and have serious, sometimes fatal side effects. A specific therapy aimed at eliminating these autoimmune T cells through restimulation-induced cell death (RICD) could cure the disease and overcome the fatal side effects of current therapies.

Ebola virus (EBOV) hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. EBOV is transmitted by contact with body fluids from infected individuals including droplets or aerosols. Aerosolized EBOV could also be exploited for intentional virus spread. Therefore, vaccines that protect against mucosal and systemic exposure are needed.

The inventors have created a reverse genetics system for RSV strain B1 of antigenic subgroup B encoding a replication-competent recombinant RSV that contains a codon-optimized G ORF and expresses enhanced green fluorescence protein (GFP). There are two antigenic subgroups of RSV, subgroups A and B, and most of the available information and reagents are for subgroup A. Immunity against either subgroup has reduced effectiveness in restricting the heterologous subgroup, suggesting that an effective RSV vaccine might need to contain both subgroups.

Millions of people are infected with HIV-1 worldwide, and 2.5 to 3 million new infections have been estimated to occur yearly. Although effective antiretroviral therapies are available, millions succumb to AIDS every year, especially in Sub-Saharan Africa, underscoring the need to develop measures to prevent the spread of this disease.

Antigens on the surface of virus particles are displayed in a regular, repetitive pattern which facilitates B cell activation. Presenting trimeric antigens on engineered particles that mimic the geometric patterns observed for native viral proteins can lead to an improved host antibody response.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is the primary target of neutralizing antibodies. The F glycoprotein exists in at least two conformations, a meta-stable prefusion state, and an extremely stable postfusion state. Both states share several epitopes targeted by neutralizing antibodies, but it has been demonstrated that the prefusion conformation of F contains at least one epitope not present in the postfusion conformation.

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.

In pursuit of an effective vaccine to end the global HIV-1/AIDS pandemic, researchers at the Vaccine Research Center (“VRC”) continue to study the structure of HIV-1. Recently, these researchers have determined the three-dimensional structure of the HIV-1 Envelope trimeric ectodomain (“Env”), comprised of three gp120 and three gp41 subunits, in its prefusion, mature, closed conformation.