Pandemic Preparedness Translational and Clinical Research

Credit: NIAID


NIAID will leverage its expertise in infectious diseases, genomics, proteomics, bioinformatics, and access to clinical samples to develop rapid-response diagnostics for biological threats and emerging infectious diseases. In close collaboration with other NIH institutes and USG agencies, NIAID will support the development new and improved point-of-care and home-based tests as well as ultrahigh-throughput central reference laboratory testing that can accurately detect signatures of infectious pathogens that are of high public-health consequence. NIAID will develop readiness strategies in collaboration with other USG agencies to ensure immediate authorized deployment of the necessary diagnostic testing as a frontline medical countermeasure following acknowledgement of an imminent public-health threat.


NIAID will continue to support basic, translational, and clinical research efforts to identify promising targets for intervention and generate novel therapeutics that are both pathogen-specific and have broad-spectrum activity. Leveraging earlier successful partnerships (as for HIV drug development) and continuing the collaborative interactions that were established in response to the COVID-19 pandemic, NIAID will engage pharmaceutical companies to share libraries, medicinal chemistry, and drug development expertise to accelerate internal efforts to ensure the most promising drug candidates progress rapidly into clinical use.

Small Molecule/Antivirals

The Pandemic Preparedness Plan will respond to the pressing need for safe and effective therapeutics by building sustainable platforms for targeted drug discovery through the development of small molecules and antivirals that may be useful against a wide range or class of pathogens of concern. NIAID will evaluate and advance new drug candidates to the stage of being late Phase 2-ready. One existing program through which NIAID will develop safe and effective antivirals is the Antiviral Program for Pandemics (APP). The APP will focus on antivirals that directly act against viral targets, specifically for RNA viruses. Antivirals of interest will have broad use in the outpatient setting, reducing viral burden in the early stages of infection.

As part of the APP, NIAID will establish Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern. The centers will initially focus on novel, oral antivirals for SARS-CoV-2 and other coronaviruses and will expand to other pathogens of pandemic concern in future years.

These Centers will use the tools of structural biology, biochemistry, and systems biology to select essential virus-specific functions for targeting. Further, this platform will provide a means for identifying the conserved structures and functions shared between pathogens of concern that can be targeted for drug development.

Monoclonal Antibodies

Recent advances in mAb technologies have provided scientists with valuable tools to prevent and treat infectious disease. Innovation efforts in the selection and manufacture of mAbs reduced the time needed for their development. Their applicability in either prevention or treatment approaches make mAbs a powerful intervention against infectious disease, particularly essential in the case of an outbreak (as during the Ebola outbreak in central Africa and the COVID-19 pandemic). NIAID will support the development and characterization of panels of mAbs against prototype and priority pathogens. The mAbs that are identified as highly neutralizing or with broadly neutralizing capacity will be further characterized and developed into candidates for effective therapeutics and/or prevention approaches.

Broad-spectrum protection via immunomodulation, trained immunity, and related approaches

Recent advances in understanding host innate immunity highlight the potential value of non-antigen-specific protection as a bridge during development of antivirals and vaccines. NIAID will support the development and clinical evaluation of short-term, but broadly protective strategies including the use of inhaled or systemic immunomodulators. Research on vaccine-elicited, off-target protection has identified a molecular process termed trained innate immunity, by which certain live-attenuated or well-adjuvanted vaccines trigger long-lived epigenetic programs that enhance functions of innate immune cells, including monocytes and macrophages. NIAID will support basic and clinical research with the long-range objective of providing protection from severe disease early in a pandemic (prior to the availability of pathogen specific vaccines) through trained innate immunity.  


Successful vaccine design and development can significantly alter the course of a pandemic. To address the need for safe and highly effective vaccines against new and emerging pathogens, NIAID will support work to define the key antigenic targets through the use of the prototype and priority pathogen approaches, solve structures of surface proteins, characterize the immunological response (including epitope mapping), support structure guided vaccine design, identify and characterize novel adjuvants that boost immunity and increase the breadth of immune responses while decreasing vaccine reactogenicity, and identify cellular receptors and tropisms. In addition, comprehensive reagents leading to the development of antigen-specific and serological assays would also provide the necessary tools for vaccine development.

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