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.

Targeted Gene Mutation Technology for Studying Specific Cell Functions in Mice

This technology includes the development of transgenic mice with a targeted gene mutation that flanks exon 8 of the Ikzf2 (Helios) gene using loxP sites. These Ikzf2 fl/fl (floxed) mice allow researchers to selectively delete the Ikzf2 gene in specific tissues or cells by crossing them with mice that express Cre recombinase under tissue-specific promoters.

Immunotherapy for Treating HER2-Positive Breast Cancer

This technology includes a novel immunotherapy approach designed to target HER2-positive breast cancer cells. It leverages a specific mechanism to enhance the immune system's ability to identify and destroy these cancer cells. The technology demonstrated significant potential in pre-clinical in vivo studies, suggesting it could improve treatment outcomes for patients with HER2-positive breast cancer

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.

Nanobodies Neutralizing Lassa Virus

Lassa Hemorrhagic Fever (LHF) is a serious disease caused by infection with Lassa virus (LASV) – highly prevalent in West Africa and spreading globally. LASV is associated with high morbidity and mortality rates, annually infecting 100,000 to 300,000 individuals and causing 5,000 deaths. Developing prophylactics and treatment for LASV is difficult due to challenges in inducing neutralizing antibodies and producing their target, the LASV glycoprotein trimer (GPC).

Enhanced S10-3 Cell Line for Advanced Hepatitis E Virus Research and Therapeutic Development

The Huh-7 cell line underwent a detailed sub-cloning process to enhance its effectiveness for Hepatitis E Virus (HEV) infection studies. This involved diluting and culturing cells in 96-well plates until confluent monolayers formed, followed by selection and expansion of the most suitable cells. The sub-clone S10-3, derived from this process, was identified as the most efficient for transfection and infection by HEV.

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.

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