News release
Tuesday December 22, 2020
Preliminary results suggest that anti-COVID19 nanobodies may be effective in preventing and diagnosing infections.
Researchers at the National Institutes of Health have isolated a series of promising tiny antibodies or “nanobodies” against SARS-CoV-2 produced by a llama named Cormac. Preliminary results published in scientific reports suggest that at least one of these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grasping SARS-CoV-2 spike proteins. In addition, the nanobody was found to work equally well in liquid or aerosol form, suggesting that it might remain effective after inhalation. SARS-CoV-2 is the virus that causes COVID-19.
The study was led by two neuroscientists, Thomas J. “TJ” Esparza, BS, and David L. Brody, MD, Ph.D., who work in a brain imaging lab at NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
“TJ and I had been testing how we could use nanobodies to improve brain imaging for years. When the pandemic broke out, we thought this was a once in a lifetime, all-hands-on-deck situation and joined the fight, ”said Dr. Brody, who is also a professor at Uniformed Services University for the Health Sciences and the study’s senior author. “We hope these anti-COVID-19 nanobodies can be highly effective and versatile in the fight against the coronavirus pandemic.”
A nanobody is a special type of antibody naturally produced by the immune system of camelids, a group of animals that includes camels, llamas and alpacas. These proteins weigh, on average, about one-tenth the weight of most human antibodies. This is because nanobodies isolated in the laboratory are essentially free-floating versions of the ends of the arms of heavy chain proteins, which form the backbone of a typical Y-shaped human IgG antibody. These tips play a critical role in the immune system’s defense by recognizing proteins on viruses, bacteria and other invaders, also known as antigens.
Because nanobodies are more stable, cheaper to produce, and easier to construct than typical antibodies, a growing number of researchers, including Mr. Esparza and Dr. Brody, are using them for medical research. For example, a few years ago, scientists showed that humanized nanobodies may be more effective in treating an autoimmune form of thrombotic thrombocytopenic purpura, a rare blood disease, than current therapies.
Since the outbreak of the pandemic, several researchers have produced llama nanobodies against the SARS-CoV-2 spike protein that may be effective in preventing infections. In the current study, the researchers used a slightly different strategy than others to find nanobodies that may work particularly well.
“The SARS-CoV-2 spike protein works like a key. It does this by opening the door to infections when it binds to a protein called the angiotensin converting enzyme 2 (ACE2) receptor, which is found on the surface of some cells, ”said Mr. Esparza, who is also a is an associate of the Henry M. Jackson Foundation for the Advancement of Military Medicine and the lead author of the study. “We have developed a method that would isolate nanobodies that block infection by covering the teeth of the spike protein that bind to and unlock the ACE2 receptor.”
To do this, the researchers immunized Cormac five times for 28 days with a purified version of the SARS-CoV-2 spike protein. After testing hundreds of nanobodies, they discovered that Cormac produced 13 nanobodies that are potentially strong candidates.
Initial experiments suggested that one candidate, named NIH-CoVnb-112, could work very well. Test-tube studies showed that this nanobody binds to the ACE2 receptor 2 to 10 times more strongly than nanobodies produced by other laboratories. Other experiments suggested that the NIH nanobody attached directly to the ACE2 receptor binding portion of the spike protein.
Next, the team showed that the NIH-CoVnB-112 nanobody could be effective in preventing coronavirus infections. To mimic the SARS-CoV-2 virus, the researchers genetically mutated a harmless “pseudovirus” so that it could use the spike protein to infect cells that have human ACE2 receptors. The researchers saw that relatively low levels of the NIH-CoVnb-112 nanobodies prevent the pseudovirus from infecting these cells in Petri dishes.
Importantly, the researchers showed that the nanobody was just as effective at preventing infections in Petri dishes when it was sprayed through the type of nebulizer or inhaler commonly used to treat patients with asthma.
“One of the exciting things about nanobodies is that, unlike most regular antibodies, they can be nebulized and inhaled to cover the lungs and airways,” said Dr. Brody.
The team has applied for a patent on the NIH-CoVnB-112 nanobody.
“While we still have a lot of work to do, these results are a very promising first step,” said Mr Esparza. “With the support of the NIH, we are moving fast to test whether these nanobodies can be safe and effective preventive treatments for COVID-19. Employees are also trying to find out if they can be used for inexpensive and accurate tests. “
This study was supported by NIH inpatient research programs of the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Environmental Health Sciences (NIEHS); Dr. Brody is an associate of the Uniformed Services University of the Health Sciences. The views expressed here do not agree with those of the Department of Defense.
NINDS is the country’s main funder of brain and nervous system research. NINDS ‘mission is to seek fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological disorders.
About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. To learn more about NIEHS or environmental health topics, visit https://www.niehs.nih.gov or subscribe to a news list.
About the National Institutes of Health (NIH):
NIH, the national medical research agency, includes 27 institutes and centers and is part of the United States Department of Health and Human Services. NIH is the premier federal agency that conducts and supports basic, clinical and translational medical research, investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Article
Esparza, TJ et al., High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme. Scientific Reports, December 22, 2020 DOI: 10.1038 / s41598-020-79036-0.