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.

Dual-Germline Antibody Engager Chimeric HIV–1 Immunogens

Despite four decades of intensive research, a safe and effective HIV-1 vaccine remains elusive due to the extreme difficulty in eliciting broadly neutralizing antibodies (bNAbs), which recognize and block HIV-1 from entering healthy cells. Only rare natural HIV-1 envelopes (Envs) promote the activation and expansion of naive B cells expressing unmutated germline antibodies of various bNAb lineages, but they typically do so for a single lineage for the same neutralization site.

Stable Human Cell Lines Expressing Flavivirus Virus-Like Particles (VLPs) for Vaccine, Biologics, and Diagnostic Development

Flaviviruses such as Zika virus, dengue virus, West Nile virus, yellow fever virus, and Japanese encephalitis virus cause widespread illness and death throughout the world. Typically, flaviviruses get transmitted through the bite of infected mosquitoes and ticks.

Simian T-Cell Lymphotropic Virus Strain Type 3 (STLV-3) Subtype D Variant, a Highly Divergent STLV-3, for Development of Diagnostics, Therapeutics, Vaccines and Research Tools

Simian T-cell lymphotropic viruses (STLV) are nonhuman primate retroviruses closely related to the human T-lymphotropic virus (HTLV). Types I, II, and III of HTLV have been found in humans and are believed to have originated from cross-species transmission of STLV from infected nonhuman primates. The HTLV viruses are known to cause leukemia, lymphoma, and neurological disorders.

Fluorescent Primer(s) Creation for Nucleic Acid Detection and Amplification

CDC researchers have developed technology that consists of a simple and inexpensive technique for creating fluorescent labeled primers for nucleic acid amplification. Fluorescent chemical-labeled probes and primers are extensively used in clinical and research laboratories for rapid, real-time detection and identification of microbes and genetic sequences. During nucleic acid amplification, the "UniFluor" primer is incorporated into newly synthesized double stranded DNA.
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