The initial research response to the COVID-19 pandemic enabled the rapid identification of the human cellular receptor for SARS-CoV-2 (angiotensin converting enzyme 2, known as ACE-2) and the characterization of the structure of the SARS-CoV-2 spike protein, which sits on the surface of the virus and facilitates entry to human cells. NIAID-supported research helped quickly identify targets for potential treatments and vaccines, leading to numerous effective countermeasures.
NIAID continues to conduct research to understand the basic characteristics of SARS-CoV-2 to find better ways to detect, prevent and treat COVID-19. This includes studies to understand further the host immune response to the virus, such as natural history studies to identify biomarkers or characteristics of infection that lead to severe disease. Observational studies underway can help advance understanding of how the virus spreads and causes disease. NIAID investigators and NIAID-supported researchers are also using small and large animal models to evaluate COVID-19 interventions.
NIAID also is investigating virus genetic diversity and how SARS-CoV-2 variants emerge. Researchers are evaluating the impact of variants on transmission and disease severity, and their potential to escape immunity elicited by natural infection or vaccination.
Rocky Mountain Laboratories
Investigators at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana, study how viral pathogens like SARS-CoV-2 and MERS cause disease and how the immune system responds to infection or vaccination. For example, RML researchers rapidly developed an animal model of COVID-19 and demonstrated that SARS-CoV-2 causes disease in the lungs, and that virus is shed similarly to virus shedding in COVID-19 patients. Investigators also published pivotal studies on SARS-CoV-2 transmission and how the route of transmission correlates with disease severity, as well as virus stability studies showing how long the virus can persist in certain conditions.
RML investigators are using animal models to evaluate SARS-CoV-2 antivirals and vaccines. Prior to the COVID-19 pandemic, RML scientists collaborated with Oxford University investigators to conduct preclinical studies of Oxford’s chimpanzee adenovirus-vectored vaccine candidate against MERS-CoV. They quickly transitioned research to preclinical studies of Oxford’s SARS-CoV-2 vaccine, now developed by AstraZeneca. The vaccine (known as AZD1222 or Vaxzevria) was evaluated in a federally funded Phase 3 clinical trial, which showed the vaccine protects against COVID-19.
Vaccine Research Center
Stabilized Spike Protein Technology/Prototype Pathogen approach
NIAID Vaccine Research Center (VRC) scientists spent years prior to the COVID-19 pandemic researching the structure and function of coronaviruses to make highly targeted vaccines. The VRC’s pandemic preparedness approach involves selecting “prototype pathogens” from viral families with pandemic potential, and then using those prototypes as a model for vaccine development with the intention that the selected vaccine approach could be generalized to other similar viruses within the same family or related viruses that share certain characteristics.
In 2016, VRC scientists and their academic collaborators invented a molecular engineering approach for stabilizing the spike protein of any coronavirus. (The spike protein enables coronavirus particles to infect human cells.) The strategy, based on previous related research on HIV and respiratory syncytial virus (RSV), involves locking the spike protein into a prefusion conformation, or shape. Stabilizing coronavirus’ spike proteins makes them potent and precise immunogens for use in vaccines. The SARS-CoV-2 spike protein was stabilized using this patented molecular engineering approach. NIH has licensed worldwide this pivotal technology to various companies for use in their COVID-19 vaccine products.
The VRC established the PREMISE (Pandemic REsponse REpository through Microbial/Immunological Surveillance & Epidemiology) program to support the COVID-19 response and pandemic preparedness more broadly. Through a network of investigators and collaborators, PREMISE will conduct virologic and immunologic screening of targeted and broad cohorts to detect reactivity against viruses of pandemic potential. PREMISE will also identify viruses by sequencing samples from animals capable of transmitting disease to humans (zoonotic reservoirs) and people. The resulting analyses will be shared to preemptively generate resources for early detection and diagnosis and to identify monoclonal antibodies and immunogens for vaccine discovery and development. Ultimately, PREMISE will integrate serologic and cellular immune discovery, targeting a broad array of pathogens, into product development. Read more about the PREMISE program.
The VRC PrePARE (Predictive Polyclonal Antibody Response Evaluation) program analyzes serologic samples from symptomatic, recovered, and vaccinated nonhuman primates and people to define detailed serum antibody responses to emerging pathogens. The program identifies variants that are generated under host immune selection pressure and facilitates prediction of vaccine efficacy against new virus variants. When combined with whole virus genome sequencing, investigators can define how pathogens evolve to escape immune responses, providing data needed to respond to new coronavirus variants and other emerging pathogens relevant for pandemic preparedness.
SARS-CoV-2 Assessment of Viral Evolution (SAVE) Program
The SARS-CoV-2 Interagency Group (SIG), established by the U.S. Department of Health and Human Services (HHS), works to rapidly characterize emerging variants and actively monitors their potential impact on SARS-CoV-2 vaccines, therapeutics and diagnostics. NIAID is a member of the SIG and supports research and surveillance activities to help inform decisions made by the SIG. NIAID created the SARS-CoV-2 Assessment of Viral Evolution (SAVE) to perform rapid and collaborative risk assessment of SARS-CoV-2 variant viruses. The NIAID SAVE program is composed of an international team of scientists with expertise in virology, immunology, vaccinology, structural biology, bioinformatics, viral genetics, and evolution. SAVE performs comprehensive real-time risk assessments of emerging mutations in SARS-CoV-2 to determine their impact on transmissibility, virulence, and susceptibility to infection- or vaccine-induced immunity. Read more about the NIAID SAVE program.
Centers for Research in Emerging Infectious Diseases (CREID)
In August 2020, NIAID established a global, multidisciplinary network called the Centers for Research in Emerging Infectious Diseases (CREID) to conduct investigations into how and where viruses and other pathogens emerge from wildlife and spillover to cause disease in people and to conduct timely outbreak research. Research projects include surveillance studies, developing reagents and diagnostic assays and studies aimed at detailing human immune responses to new or emerging infectious agents. The breadth of research projects in the CREID network will allow for study of disease spillover in multiple phases of the process: where pathogens first emerge from an animal host; at the borders between wild and more populated areas, where human-to-human transmission occurs; and, finally, in urban areas, where epidemic spread can occur. Read more about the Centers for Research in Emerging Infectious Diseases (CREID).
BEI Resources Repository
The BEI Resources Repository is a central repository that supplies organisms and reagents, including SARS-CoV-2 isolates and clinical specimens, to the broad community of microbiology and infectious diseases researchers. Read more about the BEI Resources Repository.
World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)
The WRCEVA program maintains the Emerging Viruses and Arboviruses Reference Collection and provides reagents and support for investigations of virus outbreaks throughout the world. Read more about the WRCEVA.
Centers of Excellence for Influenza Research and Response (CEIRR)
CEIRR is a multidisciplinary and collaborative research network that studies the natural history, transmission, and pathogenesis of influenza. While the Centers are primarily focused on influenza, the network also studies SARS-CoV-2 and has led efforts to develop diagnostics as well as animal models for evaluating vaccines and therapeutics. The Centers have also conducted studies on the virulence, pathogenicity and transmission of SARS-CoV-2. Read more about the CEIRR network.
Collaborative Influenza Vaccine Innovation Centers (CIVICs)
The Collaborative Influenza Vaccine and Innovation Centers (CIVICs) is a NIAID-funded network of research centers working to develop more durable, broadly protective and longer-lasting influenza vaccines. CIVICs investigators also conduct research on SARS-CoV-2. Their efforts have included longitudinal studies on the duration of responses to COVID-19 vaccination and infection and the analysis of variants to support surveillance and pandemic response efforts. Read more about the CIVICs network.
Genomics, Bioinformatics, and Systems Biology Programs
NIAID’s Genomic Centers for Infectious Diseases, Bioinformatics and Systems Biology programs have provided critical information the virus’s spread and evolution, and the cellular signatures associated with severe or resolving COVID-19 disease. These programs have also supported the development of high-throughput laboratory and computational methods for processing large numbers of SARS-CoV-2 samples to model and predict the genomic epidemiology of the pandemic.
NIAID’s Structural Genomics Centers for Infectious Diseases have provided critical support for protein production, structure determination and functional characterization of SARS-CoV-2 proteins. The centers have made profound contributions to drug discovery, vaccine development and diagnostics yielding vital structural information to support global efforts to develop new technologies for monitoring and treating patients against SARS-CoV-2. Read more about the NIAID Structural Genomics Centers.