Human clinical trials have begun on a new vaccine candidate that may protect against not only SARS-CoV-2, the virus that causes COVID-19, but against at least two of the variants emerging around the world. The development of this new vaccine was guided by structural information on the virus obtained at the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE's Argonne National Laboratory, and other light sources.
Trials are taking place at the Walter Reed Army Institute of Research (WRAIR), part of the U.S. Army Medical Research and Development Command, following up on early tests that showed promising results.
"The structural biology work is useful in terms of knowing that the vaccine design is able to bind to protective antibodies, and to see exactly where they bind on the virus. Those two pieces of information are the bread and butter that helped us create the vaccine design." -- Dr. Gordon Joyce, chief of the Structural Biology Section at the Henry M. Jackson Foundation for the Advancement of Military Medicine.
The new vaccine, called spike ferritin nanoparticle (SpFN), uses a multifaced sphere design, one that mimics the virus itself, with protruding spikes. In addition to generating a strong immune response, the design of the vaccine may help provide broader protection, shielding against the virus's mutations. Preclinical studies indicate that SpFN induces highly potent and broadly neutralizing antibody responses against the SARS-CoV-2 virus, as well as two major variants -- B.1.1.7, first seen in the U.K., and B.1.351, first seen in South Africa -- and the SARS-CoV-1 virus, which caused the severe acute respiratory syndrome outbreak in the early 2000s.
Since January of 2020, the APS has made its resources available to the worldwide scientific community for COVID-19 research, and the ultrabright X-rays it generates have helped scientists determine more than 160 structures of the proteins that make up SARS-CoV-2.
"We used the APS to generate high-resolution protein structures, and we used that information as a major component of the pipeline to develop our vaccine," said Dr. Gordon Joyce, chief of the Structural Biology Section at the Henry M. Jackson Foundation for the Advancement of Military Medicine (HFJ), supporting the WRAIR. Joyce developed this new vaccine with Dr. Kayvon Modjarrad, director of the Emerging Infectious Diseases Branch (EIDB) at WRAIR, who leads the Army's COVID-19 vaccine research efforts.
Joyce, Modjarrad and their colleagues used a technique called crystallography -- basically shining X-rays onto synthetic protein crystals grown with particular antibodies, to capture detailed pictures of the virus's spike protein -- to test whether their nanoparticles have the correct structure and function to elicit an immune response that can neutralize the virus.
"The structural biology work is useful in terms of knowing that the vaccine design is able to bind to protective antibodies, and to see exactly where they bind on the virus," Joyce said. "Those two pieces of information are the bread and butter that helped us create the vaccine design."
Joyce credited the work done at the APS and other light sources around the world with helping to speed up the development of COVID-19 vaccines. He said the long-term research goal involves using crystallography to search for a vaccine against all variants of SARS-CoV-2 and other coronaviruses, in order to get ahead of future outbreaks.
The APS also played a foundational role in the development of all three of the COVID-19 vaccines currently being distributed in the United States.
The phase 1 study of this new vaccine is being conducted at WRAIR's Clinical Trials Center and will enroll 72 healthy adult volunteers ages 18-55. Participants will be randomly placed in placebo or experimental groups. WRAIR is also providing expertise and support to the interagency U.S. Federal Government response aimed at accelerating the development of other COVID-19 vaccines, therapeutics and diagnostics.
"We are in this for the long haul," said Modjarrad. "We have designed and positioned this platform as the next generation vaccine, one that paves the way for a universal vaccine to protect against not only the current virus, but also to counter future variants, stopping them in their tracks before they can cause another pandemic."
The clinical trial of SpFN is sponsored by the U.S. Army Medical Research and Development Command (USAMRDC). The vaccine was developed by the Walter Reed Army Institute of Research (WRAIR) Emerging Infectious Diseases Program with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc (HJF). Funding was provided by the Defense Health Agency and was executed, in part, through a cooperative agreement between WRAIR and HJF (CA# W81XWH-18-2-0040).
The trial is registered on clinicaltrials.gov: https:/
The Advanced Photon Source is a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory. Additional funding for beamlines used for COVID-19 research at the APS is provided by the National Institutes of Health (NIH) and by DOE Office of Science Biological and Environmental Research. Supplemental support for COVID-19 research was provided by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19 with funding provided by the Coronavirus CARES Act.
About the Advanced Photon Source
The U. S. Department of Energy Office of Science's Advanced Photon Source (APS) at Argonne National Laboratory is one of the world's most productive X-ray light source facilities. The APS provides high-brightness X-ray beams to a diverse community of researchers in materials science, chemistry, condensed matter physics, the life and environmental sciences, and applied research. These X-rays are ideally suited for explorations of materials and biological structures; elemental distribution; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injector sprays, all of which are the foundations of our nation's economic, technological, and physical well-being. Each year, more than 5,000 researchers use the APS to produce over 2,000 publications detailing impactful discoveries, and solve more vital biological protein structures than users of any other X-ray light source research facility. APS scientists and engineers innovate technology that is at the heart of advancing accelerator and light-source operations. This includes the insertion devices that produce extreme-brightness X-rays prized by researchers, lenses that focus the X-rays down to a few nanometers, instrumentation that maximizes the way the X-rays interact with samples being studied, and software that gathers and manages the massive quantity of data resulting from discovery research at the APS.
This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.
The U.S. Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https:/