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.

Enhanced Stability and Efficacy of Pfs48/45 Domain III Protein Variants for Malaria Vaccine Development Using SPEEDesign Technology

The technology includes modifying the Plasmodium falciparum Pfs48/45 Domain III protein sequence to enhance its stability and efficacy to aid in malaria vaccine development. This approach successfully overcomes previous production challenges by increasing the thermostability of the antigen and eliminating the need for additional modifications that could impair vaccine effectiveness. Crucially, the technology maintains the essential neutralizing epitope of Pfs48/45, ensuring its effectiveness in preventing malaria transmission as a transmission-blocking vaccine.

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.

 

Human Monoclonal Antibodies That Target Plasmodium Falciparum Sporozoites

Malaria is one of the worlds deadliest infectious diseases, causing an estimated 249 million cases and 608,000 deaths annually, with children in the regions of Africa and South Asia being most vulnerable. Approx 2,000 cases of malaria are reported in the United States each year, by travelers from malaria-risk countries. Malaria is a mosquito-borne parasitic disease transmitted through the bite of infected female mosquitoes, which introduces Plasmodium sporozoites into the bloodstream of the human host.

Subscribe to NIAID