Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy

The objective of this study is to assess the safety, tolerability, and immunogenicity of a vaccination with stabilized CH505 TF chTrimer admixed with 3M-052-AF + Aluminum hydroxide (Alum), to assess the effect of CH505 TF chTrimer vaccine as a therapeutic vaccine in adults living with HIV-1 on suppressive antiretroviral therapy (ART) with the aim of inducing new HIV-1 Envelope (Env) B-cell neutralizing immune responses.

Contact Information

Office/Contact: Aleen Khodabakhshian
Phone: 310-557-3798
Email: akhodabakhshian@mednet.ucla.edu
 

First-in-Human PfSPZ-LARC2 Vaccination/CHMI

The primary objective of this study is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Phase 1 Study on Bioavailability, Food Effect, and Drug-Drug Interaction of ALG-097558 Tablets in Healthy Volunteers

The aim of this multi-part Phase 1 study is to evaluate the drug-drug interaction (DDI) potential of ALG-097558 via co-administration with a P-gp substrate (dabigatran) and a CYP3A4 inhibitor/P-gp inhibitor (itraconazole).

Master Protocol for Evaluating Multiple Infection Diagnostics for Ciprofloxacin-Resistant Neisseria Gonorrhoeae

The goal of this study is to learn if a few investigational tests can correctly find the gene mutation (mutant allele gyrA 91F) that predicts ciprofloxacin resistance in clinical specimens that harbor Neisseria gonorrhoeae.

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Office/Contact: Lina Castro, PHM, MPH, M(ASCP)CM, TS (ABB)
Phone: 415-554-2800
Email: lina.castro@sfdph.org
 

Using the NIAID Data Ecosystem Discovery Portal to Search Across Data Repositories

Data Science Dispatch |

NIAID has developed a platform to help researchers find data related to infectious and immune-mediated disease (IID) across multiple data repositories. The NIAID Data Ecosystem Discovery Portal is a centralized hub cataloging millions of datasets from over 50 sources.

Researchers can use the Discovery Portal to find data, resources, and computational tools from different repositories. This can save them time otherwise spent combing through multiple sources and help them find datasets they weren’t aware of previously.

The Discovery Portal includes resources from IID and generalist repositories. Representative resources include NIAID-sponsored repositories such as AccessClinicalData@NIAID, ImmPort, and VDJServer, as well as repositories funded outside of NIAID but relevant to IID research. Resources in the Discovery Portal include a diverse array of data types spanning multiple domains of IID research, including -omics data, clinical data, epidemiological data, pathogen-host interaction data, flow cytometry, imaging, and other experimental data.

The Discovery Portal supports NIAID objectives of maximizing the impact of scientific data, reducing duplication of efforts in research, and promoting data reuse, data transparency and compliance with data-sharing policies. The portal aligns with many of the principles of findable, accessible, interoperable, and reusable (FAIR) data practices by making data easier to find and access.

Using metadata to drive discovery

The NIAID Data Ecosystem Discovery Portal does not contain data itself. Instead, it contains detailed information about IID datasets and resources drawn from metadata. Users can then access the resources through external links.

The portal uses metadata to support several key features:

  • Search and Discovery: Users can rapidly search millions of datasets across both IID and generalist repositories using the Search or Advanced Search options. Metadata categories such as funding source, repository, and conditions of access help filter search results and identify relevant research data.
  • Metadata Compatibility: Each individual dataset in the Discovery Portal has a “metadata compatibility score,” which displays specific metadata elements collected for a given resource.  Additionally, the Discovery Portal has metadata compatibility visualizations which capture the breadth of metadata at the repository level. This information can help researchers and data contributors quickly understand a repository’s metadata structure, aiding in decisions about where to deposit or retrieve resources.
  • Downloadable Metadata: The portal has buttons that allow users to download metadata to perform meta-analyses.

The Discovery Portal is working to fill missing or incomplete metadata fields (such as Pathogen Species, Health Condition, and Host Species) by augmenting and standardizing metadata fields to provide more of this necessary information for users.

New Program Collection tool and other features

One of the new features of the NIAID Data Ecosystem Discovery Portal is the “Program Collection” filter. These are groups of datasets contributed by specialized NIAID research programs and initiatives. The Discovery Portal displays the Program Collection filter on the search page, and current efforts are focused on expanding Program Collection data.

The Program Collection filter allows researchers to discover high-quality, program-specific data relevant to their area of interest and find collections that align with the broader objectives of NIAID’s strategic research efforts. The feature also amplifies the scientific contributions of participating networks and increases the likelihood of researchers using these datasets. 

Using the Sources page of the Discovery Portal can also help researchers and data providers make informed decisions about different repositories where they can deposit their data.

The Discovery Portal is now connected to National Center for Biotechnology Information (NCBI) databases through NCBI LinkOut. When NCBI database content is linked to data described in the Portal, a link to the related Portal entry can be found on the NCBI page.

Learn more by visiting the Discovery Portal, reviewing the Getting Started page, and exploring the Knowledge Center

Preclinical Models of Infectious Disease Microphysiological Systems (MPS)

NIAID provides preclinical services using human cell-based MPS and organoids to test promising therapeutic candidates that combat viruses of biodefense (pandemic) concern.

Understanding Metadata: A Key to Data Sharing and Reuse

Data Science Dispatch |

Metadata plays a crucial role in sharing and reusing scientific data. Understanding what metadata is and how it is used can accelerate your research and increase the visibility of your work. It can also help to advance the field of infectious and immune-mediated disease (IID) research.

What is metadata?

Metadata is data about data. It provides additional information to help people understand the data, such as its origin, structure, and context. 

For example, for a genome sequence, the data is the actual sequence of nucleotides. The metadata is the author of the data, the date the data was collected, the measurement techniques used, the health condition at the focus of dataset (like asthma or autoimmune diseases), and more. You can see another example of data versus metadata in the video on the right (data management and sharing webinar from the National Institute of Diabetes and Digestive and Kidney Diseases, 4:22-6:28).

Examples of common metadata elements that describe IID research data are available at the NIAID Data Ecosystem’s list of common fundamental and recommended metadata elements

Why is metadata important? When you share scientific data, metadata provides the context that allows others to understand, trust, reproduce, or reuse data. This is particularly important in studies or secondary analyses where data is integrated from multiple sources; comprehensive metadata enables a scientist to combine data from different sources.

Using metadata effectively can also help your data get discovered, reused, and cited—thereby maximizing the value and impact of your research.

Collecting rich metadata during research

Effective metadata use starts with collecting rich metadata throughout the research process. “Rich” metadata is detailed and structured, making it easier for people to quickly learn about your data. 

Including standardized formats and schemas makes it clear which metadata components are present and where they can be found. Using common terminologies, ontologies, and data formats takes this a step further by defining specific metadata elements for both people and computers. Machine-readable metadata allows users to learn about and use data using code, helping them quickly learn about many data files.

Some common examples of collecting metadata in a structured way include defining standardized date and time formats and using ORCID IDs for authors to ensure precise identification.

Biomedical researchers can follow some basic steps to ensure that they are collecting comprehensive and standardized metadata. 

1. Determine necessary metadata content and formats

Collecting data in the format you intend to share it in is more efficient than reformatting everything at the end. Here are some questions to help you determine data and metadata formats:

  • Who will use these data and how will they use it? What information do they need to understand the data?
  • Many research areas have standardized metadata formats that researchers can follow. What metadata standards or schemas do other researchers in your field use? Would using these standards and schemas help researchers understand and reuse these data?
  • Does the target repository or scientific journal have any specific metadata or formatting requirements? If the repository where you plan to share your data has specific guidance, follow that guidance from the start of your research.

2. Create metadata throughout the data lifecycle

Before data collection, collect protocol documentation and set up systems for data and metadata collection. These systems can collect information using the standards, formats, vocabularies, and ontologies selected, and will save you time when preparing data and metadata for publication.

During the data collection phase, document anything that fits into the target metadata fields. These may include the dates data was collected, variables measured, the units of measurement, the instruments used, and the conditions under which the data was collected.

After data collection, add any remaining metadata elements from your plan. These elements may focus more on describing data processing steps, versioning, authors, or related topics. 

3. Prepare to share data and metadata 

Verify that metadata meets requirements for where you would like to share your data, and add any elements that you may finalize late in the data lifecycle, like associated publications, license for reuse, or a data author list prior to sharing.

Throughout the process, you can seek guidance from your program officer or the repositories where you intend to share data to ensure that metadata is collected and shared effectively.

Sharing data and metadata

The NIH Data Management and Sharing Policy encourages sharing metadata that describes or supports your scientific data. NIH recommends data management and sharing practices consistent with the FAIR (Findable, Accessible, Interoperable, and Reusable) data principles, and it strongly encourages the use of established data repositories for preserving and sharing data

In some instances, the full scientific data cannot be shared easily. This may be due to large file sizes — particularly with imaging-related research — or data privacy regulations. However, even if the actual scientific data cannot be shared, sharing metadata is still valuable. This practice ensures that there is a public record of the data's existence and provides important background information that can be used by other researchers.

Metadata is also a powerful tool for finding scientific data in repositories. Researchers can use metadata to search for data sets that match specific criteria. One tool that can help researchers find relevant data is the NIAID Data Ecosystem Discovery Portal, which uses metadata present in data stored in repositories to search across over 50 different IID repositories and data sources. 

Learn more about developing a data management and sharing plan and compliance with relevant NIH data sharing policies by reviewing the Data Policy and Guidance page

Tecovirimat Is Safe but Ineffective as Treatment for Clade II Mpox

Monotherapy with the antiviral drug tecovirimat was safe but ineffective as an mpox treatment in an international clinical trial.

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Epstein-Barr Virus’s Molecular Mimicry Reveals a Key Site of Vulnerability

NIAID Now |

Epstein-Barr virus (EBV) is a common virus that causes mononucleosis, or mono for short, and is associated with some types of cancer and autoimmune diseases. Despite EBV’s known effects and potential to cause disease, there are few therapeutic options and no licensed vaccines targeting the virus. Looking for ways to counter EBV, NIAID researchers are examining how the virus recognizes and interacts with cells at the molecular level. New research published in Immunity reveals the high-resolution crystal structure of a protein on the surface of EBV in complex with the receptor it binds to on the surface of human immune cells, called B cells. The researchers also discovered antibodies that potently neutralize EBV and found that they recognize the viral surface protein using interactions similar to those between EBV and its receptor on host cells. This research identifies a vulnerable site on EBV that could lead to the design of much-needed interventions against the virus.

EBV, also known as human herpesvirus 4, is one of the most common human viruses—nine out of ten people have or will have EBV in their lifetime. After being infected with EBV, many people experience no symptoms, but some experience symptoms of mononucleosis, such as fever, sore throat and fatigue. These symptoms are often mild but can be more severe in teens or adults. After the early stages of infection, the virus hides in the body and can emerge later in life or when the immune system is weakened. Recent studies have also found that EBV is linked to several types of cancer, autoimmune diseases including lupus, and other disorders.

A key step in EBV infection is for the virus to enter a cell in the body, which begins with the virus binding to a protein on the cell’s surface. The researchers, led by Dr. Masaru Kanekiyo, chief of the Molecular Immunoengineering Section at NIAID’s Vaccine Research Center, examined the atomic-level structure of an EBV surface protein called gp350 when bound to a protein on the surface of B cells called complement receptor type 2 (CR2). Usually, CR2 binds to a protein fragment, or ligand, called complement component C3d as a part of the immune response following a viral infection. The researchers found that the EBV protein precisely bound to the cell surface protein CR2 at the region where its natural ligand C3d binds, revealing that there is structural similarity between EBV and C3d in recognizing CR2 and how the virus exploits this interaction to enter and infect a cell.

The researchers also isolated neutralizing antibodies (nAbs)—immune proteins that neutralize EBV—from animals immunized against EBV and EBV-infected people. They found that the antibodies neutralized the virus in laboratory tests by binding to the EBV gp350 protein. They further determined the atomic-level structure of three of the nAbs when bound to EBV gp350. All three nAbs bound to gp350 at the same region of the protein—the region where it also binds to the cell protein CR2, demonstrating that this binding site is an important target on the virus for neutralization.

The way the CR2 cell surface protein binds its natural ligand C3d can be likened to a key fitting a lock. In this case, the key is a negatively charged pocket on the surface of C3d, while the lock is an arrangement of positively charged arginine residues on the surface of CR2. The researchers observed a remarkable molecular mimicry that occurred in duplicate. On one side, EBV gp350 mimics the characteristics of C3d, pretending to be the natural key that fits CR2 on the cell surface, unlocking the cell for the virus to infect it. On the other side, the anti-EBV nAbs mimic CR2, where they act as a lock to block the EBV gp350 protein from binding to a cell for the virus to infect. The mimicry existing on both sides of this lock-and-key set indicates that this interaction is an important step for EBV infection—and represents a major point of viral vulnerability, according to the researchers.

The findings define critical molecular interactions between EBV and its host cells. The researchers noted that more work is needed to apply these findings to the development of interventions, including examining whether the newly discovered nAbs can provide protection from EBV infection in animal models and people. This research may reveal new avenues to treat and prevent disease caused by this widespread pathogen.

Reference:

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Single Dose of Broadly Neutralizing Antibody Protects Macaques from H5N1 Influenza

A single dose of a broadly neutralizing antibody given prior to virus exposure protects macaques from severe H5N1 avian influenza, NIH scientists report.

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