By: Lucas Buyon and Aaron Neal

Part of NIAID’s longstanding mission is to study the biology of pathogens with pandemic potential and support the development of medical countermeasures (MCMs) against them. MCMs broadly include any medicines, vaccines, protective equipment, or other medical supplies that can be used to diagnose, prevent, or treat diseases. The emergence and rapid spread of SARS-CoV-2 demonstrated the need for NIAID to develop a pandemic preparedness strategy to rapidly respond to out-breaks and develop MCMs. With approximately 120 viruses known to cause human disease, and a large number of those known to have pandemic potential, there is not enough time or resources available to develop the sophisticated research programs necessary to effectively address each potential pandemic threat. Given the need to prioritize research funding and maximize the impact it can have on future pandemic threats, NIAID developed a Pandemic Preparedness Plan in December 2021 with three broad goals [1]:

  • Characterize pathogens of concern through research and surveillance
  • Shorten timelines between pathogen emergence and development and authorization of MCMs
  • Bridge or eliminate gaps in research, testing and laboratory infrastructure, and technology

The plan will build upon years of advances in pathogen-specific research (called “priority pathogens”) and support research portfolios built around pathogens that are representative of a major viral family with pandemic potential (called “prototype pathogens”). Priority pathogens are pathogens that are established threats to human health. Ebolaviruses, Zika virus, Dengue virus, Lassa virus, and Influenza viruses are examples of priority pathogens. Prototype pathogens are pathogens that are representative of a broad viral family and can provide insight into the biology of the entire viral family. Viral families share significant similarities in their genetics, biological functions, and pathologies. Research on an ideal member of a viral family will lead to broad knowledge about other viruses from that same family. This knowledge can be applied to the development of MCMs for an emerging pathogen from that same family, and lead to faster MCM development timelines. For example, years of research into SARS-CoV-1 and MERS-CoV provided key insights into vaccine development for SARS-CoV-2, highlighting the power of this approach. Priority pathogens can be the prototype pathogen for their viral family (e.g., Lassa virus for the Arenaviridae family), but this is not always necessarily the case (e.g., Zika virus is a priority pathogen, but Dengue virus serves as a better prototype pathogen for Flaviviri-dae). NIAID’s research investment into these pathogens will lead to important knowledge about the immunology and biology of these viruses, supporting breakthroughs in MCM development. NIAID also supports research on broad technological platforms, such as mRNA technology, mucosal vaccines, and monoclonal antibodies, that can support the iterative and rapid development of MCMs. NIAID intramural investigators will support these efforts by studying the biology and epidemiology of pathogens, as well as help test mono-clonal antibodies and vaccine candidates through NIAID’s Vaccine Research Center (VRC).

NIAID supports several intramural research programs and extramural networks to implement its pandemic preparedness plan. Extramural networks include the Centers for Research in Emerging Infectious Diseases (CREID) [2], the Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern (AViDD) [3], and the recently announced Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) network [4]. NIAID intramural programs focused on pandemic preparedness include the Pandemic Response Repository through Microbial and immune Surveillance and Epidemiology (PREMISE) program [5], other vaccine programs at the VRC, and NIAID intramural research programs focused on pathogen biology and epidemiology. INA-RESPOND, though established long before the current NIAID Pandemic Preparedness Plan, also serves a critical role in preparing for future outbreaks and pandemics in the Southeast Asia and Pacific regions.

The CREID network, launched in 2020, is a competitive grant-funded global network of 10 research centers across 30 different countries that study the epidemiology, pathogenesis, and biology of emerging pathogens to inform surveillance for these diseases through assay development and knowledge generation. The program also supports capacity-building efforts through training scientists around the world in developing and conducting diagnostic testing, genomic surveillance, and scientific program management. The network is positioned to help rapidly support research response during an outbreak.

The AViDD network, launched in 2022, supports antiviral discovery and development, with a specific effort to develop antivirals that can be administered in an outpatient setting. AViDD supports nine research centers that conduct early-stage research into small molecules and other biotherapeutics that block viral targets. AViDD centers also have industry partners to help accelerate research and move promising candidates into drug development pipelines. The program focuses on drug development for several viral families including paramyxoviruses, bunyaviruses, togaviruses, filo-viruses, picornaviruses, and flaviviruses.

The future ReVAMPP network will support vaccine and monoclonal antibody development for pathogens with pandemic potential. ReVAMPP recently announced three notices of funding opportunities to fund centers to develop vaccines and monoclonal antibodies against Flaviviruses, Togaviruses, Bunyaviruses, Paramyxoviruses and Picornaviruses. The funding opportunities were recently announced in April 2023, and ReVAMPP centers will be important additions to the NIAID-supported pandemic preparedness ecosystem.

NIH intramural research programs also contribute to NIAID’s pandemic preparedness efforts. Several intramural labs have studied pathogens of pan-demic concern for decades, leading to insights into their biology and pathogenesis. The Vaccine Research Center (VRC) plays a key role in leading pandemic preparedness efforts, including helping co-develop the Moderna mRNA SARS-CoV-2 vaccine. The VRC has active vaccine and monoclonal antibody development programs focused on a range of priority and prototype pathogens. Ongoing projects at the VRC include efforts to develop a universal flu vaccine, Ebola therapeutic antibodies, Nipah virus vaccines [6], and other MCMs. The VRC also supports the PREMISE program as part of its pandemic preparedness efforts. PREMISE began in 2021 and combines research on human immune responses to pathogens with pathogen sequence data from humans and animal reservoirs to inform MCM development. The goal of PREM-ISE is to develop a stockpile of immunological countermeasures (monoclonal antibodies and vaccine candidates) that are ready for further development in the event of an emerging pathogen outbreak. Together, NIAID’s intramural programs form a critical part of its pandemic preparedness strategy.

NIAID has made significant investments in its pan-demic preparedness efforts since the beginning of the COVID-19 pandemic. NIAID’s pandemic preparedness plan will support global health security efforts against known microbial threats while also laying the scientific and technological groundwork to prevent and rapidly respond to emerging pathogen threats.


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