Improvement of Broadly HIV-Neutralizing Antibodies; Anti-HIV-1 Antibody VRC01.23 for Prevention or Treatment of HIV Infection

Scientists at NIAID have developed broadly neutralizing antibodies (bNAbs) with enhanced neutralizing activity against HIV-1. Specifically, previously unknown gp120 interactions with a newly elucidated quaternary receptor (CD4)-binding site in the HIV-1 envelope have been discovered by engrafting the extended heavy-chain framework region 3 (FR3) loop of VRC03 onto several potent bNAbs (including VRC01, VRC07 and N6).

Replication-Competent Adenovirus Type 4 SARS-CoV-2 Vaccines and Their Use

NIAID has produced recombinant adenovirus type 4 (Ad4), SARS-CoV-2 spike, vectors for administration to humans. These recombinant vaccines permit rapid development of high levels of neutralizing antibodies to SARS-CoV-2 in experimental animals. This vaccine is designed to improve the durability of the immune response by inducing mucosal and systemic immunity. Further, this system should be incredibly simple and efficient when producing vaccine at scale. This technology is available for licensing for commercial development in accordance with 35 U.S.C.

Humanized Murine Monoclonal Antibodies That Neutralize Type-1 Interferon (IFN) Activity

Interferons (IFNs) are a family of cytokines that function in response to an immune challenge such as a viral or bacterial infection. Type I IFNs are produced by immune cells (predominantly monocytes and dendritic cells) as well as fibroblasts and signal through a specific cell surface receptor complex (IFNAR) that consist of IFNAR1 and IFNAR2 chains. Type-I IFNs exert several common effects including antiviral, antiproliferative, and immunomodulatory activities. However, Type I IFNs also have pro-inflammatory effects, especially in the presence of TNF-a.

Replication-Competent Adenovirus Type-4 HIV Env Vaccines and Their Use

NIAID, IAVI, Emergent, and Scripps have developed two recombinant adenovirus type 4 (Ad4) vector-based vaccine candidates. These replicating Ad4 vector-based candidates have shown improved activity against tier 2 HIV-1 isolates in experimental animals. Tier 2 isolates are among the most prevalent in infected populations. The two candidates, Ad4-Env150KN and Ad4-Env145NFL, incorporate novel design features based on Ad4-EnvC150 (1086c). Specifically, the truncation of the cytoplasmic tail of Env increases cell surface expression and has resulted in improved antigenicity from both candidates.

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.

Human Monoclonal Antibodies that Broadly Target Coronaviruses

An abstract for this invention was published in the Federal Register on June 10, 2022. The family of coronaviruses cause upper respiratory tract disease in humans and have caused three major disease outbreaks in recent history: the 2003 SARS outbreak, the 2012 MERS outbreak, and the current SARS-CoV-2 pandemic. There is an urgent need for strategies that broadly target coronaviruses, both to deal with new SARS-CoV-2 variants and future coronavirus outbreaks.

Human Monoclonal Antibodies That Target the RH5 Complex of Blood-Stage Plasmodium Falciparum

249 million people were afflicted with malaria in 2022. There are five Plasmodium parasite species that cause malaria in humans. Of the five, Plasmodium falciparum causes most of the incidence of human disease. Most advanced malaria vaccine candidates can confer only partial, short-term protection in malaria-endemic areas. The pathogenesis of malaria is associated with blood-stage infection and antibodies specific to the parasite blood-stage antigens may be able to control parasitemia.

TACSTD2 in HCV Infection and Hepatocellular Carcinoma: Transcriptomics Insights

This technology involves studying the role of the Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) gene in Hepatitis C Virus (HCV) infection and hepatocellular carcinoma. Researchers perform transcriptomics analysis on liver specimens from HCV-infected patients, identify TACSTD2 as a key gene, and create a stable cell line that overexpresses TACSTD2 to investigate its impact on HCV infection and replication. This technology aims to provide insights into the molecular mechanisms of HCV infection and its association with liver cancer.

 

Novel System for HIV-1 Vaccine Development

The available technologies describe specific immunogenic peptides, peptide modifications and methods for identifying additional immunogens against HIV-1 surface proteins, gp120 and gp41. Additionally, detailed methods for use of the described immunogenic peptides in the development of vaccines and diagnostics for HIV-1 are disclosed. The current technologies further include a comprehensive system for immunogen design, comprising in silico design coupled to feedback from X-ray crystallography, antigenic analysis, and immunization.

EV-D68 Monoclonal Antibodies Isolated from Immunized Rhesus Macaques

Enterovirus D68 (EV-D68) has been linked to the widespread outbreaks of respiratory illness and acute flaccid myelitis (AFM) in the United States and Europe in 2014, 2016, and 2018. Although EV-D68 is now the most frequently encountered enterovirus (41.1% of cases), with an estimated global prevalence of 4%, there are no specific, FDA-approved therapeutic interventions targeting this virus.

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