Multi-epitope Vaccines against TARP (ME-TARP) for Treating Prostate and Breast Cancer

The development of more targeted means of treating cancer is vital. One option for a targeted treatment is the creation of a vaccine that induces an immune response only against cancer cells. In this sense, vaccination involves the introduction of a peptide into a patient that causes the formation of antibodies or T cells that recognize the peptide. If the peptide is from a protein found selectively on/in cancer cells, those antibodies or T cells can trigger the death of those cancer cells without harming non-cancer cells. This can result in fewer side effects for the patient.

Vaccines for HIV

The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity.  This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. 

Novel Regulatory B cells for Treatment of Cancer and Autoimmune Disease

The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4+ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.

Monoclonal Antibodies That Bind to the Underside of Influenza Viral Neuraminidase

Current influenza vaccines mainly induce antibodies against the surface glycoprotein hemagglutinin (HA) that block viral attachment to its host receptors and viral membrane fusion to the host cell. The immunodominant head region of HA undergoes antigenic drift and antibodies directed to the head confer little cross-protections between strains or subtypes.

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.

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.

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.

Henipavirus Vaccine

Henipaviruses are RNA viruses containing two high consequence human pathogens: Nipah virus (NiV) and Hendra virus (HeV). Both NiV and HeV infection in humans can result in severe respiratory disease and/or severe neurological manifestations, with mortality rates as high as 80%. There are currently no FDA-approved vaccines or therapeutics, and both NiV and HeV are considered dangerous emerging human pathogens with pandemic potential.

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