Skin side effects stymie advance of HIV vaccine.

Strategy of using multiple mRNA shots to hone powerful antibodies hits a pothole.

Advanced Technologies in Radiation Research.

The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research. This meeting report provides a comprehensive overview of the research presented at the workshop, which included an assembly of subject matter experts from government, industry, and academia. Topics discussed during the workshop included assessments of acute and delayed effects of radiation exposure using modalities such as clustered regularly interspaced short palindromic repeats (CRISPR) - based gene editing, tissue chips, advanced computing, artificial intelligence, and immersive imaging techniques. These approaches are being applied to develop products to diagnose and treat radiation injury to the bone marrow, skin, lung, and gastrointestinal tract, among other tissues. The overarching goal of the workshop was to provide an opportunity for the radiation research community to come together to assess the technological landscape through sharing of data, methodologies, and challenges, followed by a guided discussion with all participants. Ultimately, the organizers hope that the radiation research community will benefit from the workshop and seek solutions to scientific questions that remain unaddressed. Understanding existing research gaps and harnessing new or re-imagined tools and methods will allow for the design of studies to advance medical products along the critical path to U.S. Food and Drug Administration approval.

NIAID/SMB Workshop on Multiscale Modeling of Infectious and Immune-Mediated Diseases.

On July 19th, 2023, the National Institute of Allergy and Infectious Diseases co-organized a workshop with the Society of Mathematical Biology, with the authors of this paper as the organizing committee. The workshop, "Bridging multiscale modeling and practical clinical applications in infectious diseases" sought to create an environment for mathematical modelers, statisticians, and infectious disease researchers and clinicians to exchange ideas and perspectives.

'I'm not Tony': Anthony Fauci's heir vows new direction at NIAID.

Jeanne Marrazzo, an HIV prevention researcher, sees need for more "holistic" approach to community health problems.

Highlighting the NIAID Radiation and Nuclear Countermeasures Program's Commitment to Training and Diversifying the Radiation Workforce.

Developing and maintaining a robust and diverse scientific workforce is crucial to advance knowledge, drive innovation, and tackle societal issues that impact the economy and human health. The shortage of trained professionals in radiation and nuclear sciences derives from many factors, such as scarcity of specialized coursework, programming, professional development, and experiential learning at educational institutions, which significantly disrupt the training pipeline. Other challenges include small numbers of faculty and educators with specialized radiation/nuclear expertise that are continually overextended professionally and scientifically, with the burden of training falling on this subset of individuals. Even more alarming is the recent loss of radiobiologists due to increased retirements and deaths, leaving the radiobiology community with a void of mentors and knowledge. Lastly, inconsistency in acquiring stable grant funding to recruit and retain scientists is a major hurdle to training the next generation of radiation and nuclear scientists. Recommendations from the scientific community and the National Academies of Sciences, Engineering, and Medicine describe the need to bolster educational resources and provide more hands-on training experiences. Of equal importance was the suggestion that funding agencies provide more opportunities for training and tracking the radiation workforce. The Radiation and Nuclear Countermeasures Program (RNCP), and the Office of Research Training and Special Programs (ORTSP), both within the National Institute of Allergy and Infectious Diseases (NIAID) are committed to helping to develop and sustain the radiation research workforce. This commentary illustrates the importance of addressing radiation workforce development and outlines steps that the RNCP is taking to help mitigate the issue. In addition, the role for Diversity, Equity, Inclusion, and Accessibility (DEIA) in helping to increase the number of students trained in the radiation sciences is discussed, and the NIH's DEIA priorities and RNCP efforts to improve DEIA in the research community are highlighted. One of the main goals of this commentary is to provide awareness of available educational (i.e., development of a radiation biologist eBook) and funding resources. A summary of available awards targeting early- to mid-stage investigators and diversity candidates is given, and it is hoped that this list, although not exhaustive and not specific for all focus areas in radiation (e.g., cancer research), will encourage more radiation biologists to explore and apply to these under-utilized opportunities.

Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.

Radiation-induced multi-organ injury.

PURPOSE: Natural history studies have been informative in dissecting radiation injury, isolating its effects, and compartmentalizing injury based on the extent of exposure and the elapsed time post-irradiation. Although radiation injury models are useful for investigating the mechanism of action in isolated subsyndromes and development of medical countermeasures (MCMs), it is clear that ionizing radiation exposure leads to multi-organ injury (MOI). METHODS: The Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases partnered with the Biomedical Advanced Research and Development Authority to convene a virtual two-day meeting titled 'Radiation-Induced Multi-Organ Injury' on June 7-8, 2022. Invited subject matter experts presented their research findings in MOI, including study of mechanisms and possible MCMs to address complex radiation-induced injuries. RESULTS: This workshop report summarizes key information from each presentation and discussion by the speakers and audience participants. CONCLUSIONS: Understanding the mechanisms that lead to radiation-induced MOI is critical to advancing candidate MCMs that could mitigate the injury and reduce associated morbidity and mortality. The observation that some of these mechanisms associated with MOI include systemic injuries, such as inflammation and vascular damage, suggests that MCMs that address systemic pathways could be effective against multiple organ systems.

Prototype Pathogens for Vaccine and Monoclonal Antibody Countermeasure Development: NIAID Workshop Process and Outcomes for Viral Families of Pandemic Potential.

Given the increased risk of pandemics driven by emerging and reemerging infectious diseases, it is imperative that the United States and global scientific community be better prepared for future threats by prioritizing and launching key research programs and strategies. In December 2021, the National Institute of Allergy and Infectious Diseases (NIAID) published its pandemic preparedness plan, which focuses on the prototype pathogen approach for medical countermeasure development. The plan was introduced before its release at a NIAID-hosted workshop in November 2021 that featured scientific experts from the extramural community, government, and the private sector and focused on selection of prototype pathogens from 10 viral families with pandemic risk and moderate resources. This article will serve as an introduction to this special issue and will briefly define the prototype pathogen approach, describe the workshop goals and process for outcomes, and provide an outline of the viral working group articles to follow and future directions for NIAID.

Optimizing the Immunogenicity of HIV Vaccines by Adjuvants - NIAID Workshop Report.

This report summarizes the highlights of a workshop convened by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on April 4-5, 2022, to provide a discussion forum for sharing insights on the current status, key challenges, and next steps to advance the current landscape of promising adjuvants in preclinical and clinical human immunodeficiency virus (HIV) vaccine studies. A key goal was to solicit and share recommendations on scientific, regulatory, and operational guidelines for bridging the gaps in rational selection, access, and formulation of clinically relevant adjuvants for HIV vaccine candidates. The NIAID Vaccine Adjuvant Program working group remains committed to accentuate promising adjuvants and nurturing collaborations between adjuvant and HIV vaccine developers.

An evaluation of programs to support new investigators at the National Institute of Allergy and Infectious Diseases: Striking a balance with funding for established investigators.

As the largest funder of basic biomedical research in the US, the National Institutes of Health (NIH) has an interest in maintaining a sustainable, productive workforce of investigators. Over the years, NIH has implemented several programs to attract early-stage investigators and other applicants without prior NIH support. The latest of these is the Next Generation Researchers Initiative. These programs have been shown to be successful in meeting NIH-wide goals but their success for any particular NIH institute or center (IC), and in any particular year, is determined by a variety of factors, some extrinsic to an IC's funding decision process. Each IC must balance support for new investigators with funding for productive ongoing programs of research. We examine historical trends in support of new investigators at the National Institute of Allergy and Infectious Diseases (NIAID) over a 22-year period, as well as trends in some major extrinsic influences on that support. The results indicate that NIH's new investigator programs have succeeded in maintaining a balance between the support for new NIAID investigators while also continuing to support an expanded pool of established investigators. The programs have been particularly effective in providing support to early-stage investigators.

Prototype Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness.

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) emerged 20 years ago, presaging a series of subsequent infectious disease epidemics of international concern. The recent emergence of SARS-CoV-2 has underscored the importance of targeted preparedness research to enable rapid countermeasure development during a crisis. In December 2021 the National Institute of Allergy and Infectious Diseases (NIAID), building upon the successful strategies developed during the SARS-CoV-2 response and to prepare for future pandemics, published a pandemic preparedness plan that outlined a research strategy focused on priority pathogens, technology platforms, and prototype pathogens. To accelerate the discovery, development, and evaluation of medical countermeasures against new or previously unknown pathogens of pandemic potential, we present here a strategy of research directed at select prototype pathogens. In this manner, leveraging a prototype pathogen approach may serve as a powerful cornerstone in biomedical research preparedness to protect public health from newly emerging and reemerging infectious diseases.

Impact of extramural DAIT/NIAID pharmacy programs, research pharmacist scientist oversight on study performance, and lessons learned.

PURPOSE: Over the past two decades, the involvement of a Pharmacist Scientist in clinical settings has improved patient safety, decreased medication errors, and enabled successful conduct of clinical trials and faster product development [1-5]. The impact of an oversight by a Pharmacist Scientist on clinical trial performance and execution in terms of Pharmacy and Investigational Product (IP)-related deviations has not been evaluated by a sponsor. METHODS: This was a retrospective observational study conducted by the Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID). We assessed the association of the number of Pharmacy and Investigational Product (IP)-related deviations with Pharmacist oversight and use of DAIT Pharmacy/ Pharmaceutical services in two groups: Intervention Group (IG) and the Control Group (CG). RESULTS: We evaluated monitoring data from 116 studies conducted between 2006 through 2020. Forty-one eligible clinical trials were included and analyzed: 13 trials were in the IG with Pharmacist oversight and use of Pharmacy Services; 28 trials were in the CG with no Pharmacist oversight and zero to partial use DAIT Pharmacy/ Pharmaceutical Services. The evaluation revealed the expected risk of having a pharmacy and IP-related deviations were 2.94 times higher (95% CI 1.28, 6.67, = 0.01) in trials not having Pharmacist oversight and zero to partial use of Pharmaceutical/ Pharmacy Program services. This significant finding was associated with having Pharmacist oversight when adjusting for study size (# of sites and patients needed), anticipated study duration, design complexity, and whether recruitment was completed or not. CONCLUSION: We found a statistically significant association between Pharmacist Scientist involvement and oversight from protocol development to study execution and a reduction in Pharmacy and IP-related deviations.

Inter-agency perspective: Translating advances in biomarker discovery and medical countermeasures development between terrestrial and space radiation environments.

Over the past 20+ years, the U.S. Government has made significant strides in establishing research funding and initiating a portfolio consisting of subject matter experts on radiation-induced biological effects in normal tissues. Research supported by the National Cancer Institute (NCI) provided much of the early findings on identifying cellular pathways involved in radiation injuries, due to the need to push the boundaries to kill tumor cells while minimizing damage to intervening normal tissues. By protecting normal tissue surrounding the tumors, physicians can deliver a higher radiation dose to tumors and reduce adverse effects related to the treatment. Initially relying on this critical NCI research, the National Institute of Allergy and Infectious Diseases (NIAID), first tasked with developing radiation medical countermeasures in 2004, has provided bridge funding to move basic research toward advanced development and translation. The goal of the NIAID program is to fund approaches that can one day be employed to protect civilian populations during a radiological or nuclear incident. In addition, with the reality of long-term space flights and the possibility of radiation exposures to both acute, high-intensity, and chronic lower-dose levels, the National Aeronautics and Space Administration (NASA) has identified requirements to discover and develop radioprotectors and mitigators to protect their astronauts during space missions. In sustained partnership with sister agencies, these three organizations must continue to leverage funding and findings in their overlapping research areas to accelerate biomarker identification and product development to help safeguard these different and yet undeniably similar human populations - cancer patients, public citizens, and astronauts.

A Tribute to Dr. Fauci.

A nurse honors her husband's legacy.

The role of epigenetics in multi-generational transmission of asthma: An NIAID workshop report-based narrative review.

There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross-generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross-generational effects. Epigenetic transgenerational inheritance has been demonstrated in plants and animals, but the presence and extent of this process in humans are currently being investigated. Experimental data in animals support transmission of asthma risk across generations from a single exposure to the deleterious factor and suggest that the nature of this transmission is in part due to changes in DNA methylation, the most studied epigenetic process. The association of father's prepuberty exposure with offspring risk of asthma and lung function deficit may also be mediated by epigenetic processes. Multi-generational birth cohorts are ideal to investigate the presence and impact of transfer of disease susceptibility across generations and underlying mechanisms. However, multi-generational studies require recruitment and assessment of participants over several decades. Investigation of adult multi-generation cohorts is less resource intensive but run the risk of recall bias. Statistical analysis is challenging given varying degrees of longitudinal and hierarchical data but path analyses, structural equation modelling and multilevel modelling can be employed, and directed networks addressing longitudinal effects deserve exploration as an effort to study causal pathways.

Fauci looks back-and ahead.

Loved and hated, NIAID's chief plots life after government.

Microbiome, Metabolism, and Immunoregulation of Asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report.

This report presents the proceedings from a workshop titled "Microbiome, Metabolism and Immunoregulation of Asthma" that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome-metabolite links, and 6) potential confounders of microbiome-disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.

Animal Care in Radiation Medical Countermeasures Studies.

Animal models are necessary to demonstrate the efficacy of medical countermeasures (MCM) to mitigate/treat acute radiation syndrome and the delayed effects of acute radiation exposure and develop biodosimetry signatures for use in triage and to guide medical management. The use of animal models in radiation research allows for the simulation of the biological effects of exposure in humans. Robust and well-controlled animal studies provide a platform to address basic mechanistic and safety questions that cannot be conducted in humans. The U.S. Department of Health and Human Services has tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- through advanced-stage MCM development for radiation-induced injuries; and advancement of biodosimetry platforms and exploration of biomarkers for triage, definitive dose, and predictive purposes. Some of these NIAID-funded projects may transition to the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, which is tasked with the advanced development of MCMs to include pharmacokinetic, exposure, and safety assessments in humans. Guided by the U.S. Food and Drug Administration's (FDA) Animal Rule, both NIAID and BARDA work closely with researchers to advance product and device development, setting them on a course for eventual licensure/approval/clearance of their approaches by the FDA. In August 2020, NIAID partnered with BARDA to conduct a workshop to discuss currently accepted animal care protocols and examine aspects of animal models that can influence outcomes of studies to explore MCM efficacy for potential harmonization. This report provides an overview of the two-day workshop, which includes a series of special topic presentations followed by panel discussions with subject-matter experts from academia, industry partners, and select governmental agencies.

Prepared to Act: Lessons Learned by the Special Pathogens Research Network, Based on Collaborations with the NIAID-Led Adaptive COVID-19 Treatment Trial.

The need for well-controlled clinical trials is fundamental to advancing medicine. Care should be taken to maintain high standards in trial design and conduct even during emergency medical events such as an infectious disease outbreak. In 2020, SARS-CoV-2 emerged and rapidly impacted populations around the globe. The need for effective therapeutics was immediately evident, prompting the National Institutes of Health to initiate the Adaptive COVID-19 Treatment Trial. The Special Pathogens Research Network, made up of 10 Regional Emerging Special Pathogens Treatment Centers, was approached to participate in this trial and readily joined the trial on short notice. By trial closure, the Special Pathogens Research Network sites, making up 19% of all study sites, enrolled 26% of the total participants. The initial resources available and experience in running clinical trials at each treatment center varied from minimal experience and few staff to extensive experience and a large staff. Based on experiences during the first phase of this trial, the Special Pathogens Research Network members provided feedback regarding operational lessons learned and recommendations for conducting future studies during a pandemic. Communication, collaboration, information technology, regulatory processes, and access to resources were identified as important topics to address. Key stakeholders including institutions, institutional review boards, and study personnel must maintain routine communication to efficiently and effectively activate when future research needs arise. Regular and standardized training for new personnel will aid in transitions and project continuity, especially in a rapidly evolving environment. Trainings should include local just-in-time training for new staff and sponsor-designed modules to refresh current staff knowledge. We offer recommendations that can be used by institutions and sponsors to determine goals and needs when preparing to set up this type of trial for critical, short-notice needs.