Nav: Home

Tiny antibody component highly effective against SARS-COV-2 in animal studies

September 14, 2020

PITTSBURGH, Sept. 14, 2020 - University of Pittsburgh School of Medicine scientists have isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19. This antibody component, which is 10 times smaller than a full-sized antibody, has been used to construct a drug--known as Ab8--for potential use as a therapeutic and prophylactic against SARS-CoV-2.

The researchers report today in the journal Cell that Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases its potential for diffusion in tissues to better neutralize the virus, but also makes it possible to administer the drug by alternative routes, including inhalation. Importantly, it does not bind to human cells--a good sign that it won't have negative side-effects in people.

Ab8 was evaluated in conjunction with scientists from the University of North Carolina at Chapel Hill (UNC) and University of Texas Medical Branch (UTMB) at Galveston, as well as the University of British Columbia and University of Saskatchewan.

"Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections," said co-author John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Pitt. "Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune."

The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by "fishing" in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.

Abound Bio, a newly formed UPMC-backed company, has licensed Ab8 for worldwide development.

Dimiter Dimitrov, Ph.D., senior author of the Cell publication and director of Pitt's Center for Antibody Therapeutics, was one of the first to discover neutralizing antibodies for the original SARS coronavirus in 2003. In the ensuing years, his team discovered potent antibodies against many other infectious diseases, including those caused by MERS-CoV, dengue, Hendra and Nipah viruses. The antibody against Hendra and Nipah viruses has been evaluated in humans and approved for clinical use on a compassionate basis in Australia.

Clinical trials are testing convalescent plasma--which contains antibodies from people who already had COVID-19--as a treatment for those battling the infection, but there isn't enough plasma for those who might need it, and it isn't proven to work.

That's why Dimitrov and his team set out to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, which would allow for mass production. In February, Wei Li, Ph.D., assistant director of Pitt's Center for Therapeutic Antibodies and co-lead author of the research, began sifting through large libraries of antibody components made using human blood samples and found multiple therapeutic antibody candidates, including Ab8, in record time.

Then a team at UTMB's Center for Biodefense and Emerging Diseases and Galveston National Laboratory, led by Chien-Te Kent Tseng, Ph.D., tested Ab8 using live SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the virus from entering cells. With those results in hand, Ralph Baric, Ph.D., and his UNC colleagues tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2 . Even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to their untreated counterparts. Ab8 also was effective in treating and preventing SARS-CoV-2 infection in hamsters, as evaluated by Darryl Falzarano, Ph.D., and colleagues at the University of Saskatchewan. Sriram Subramaniam, Ph.D., and his colleagues at the University of British Columbia uncovered the unique way Ab8 neutralizes the virus so effectively by using sophisticated electron microscopic techniques.

"The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to overcome it," said Mellors, also Distinguished Professor of Medicine, who holds the Endowed Chair for Global Elimination of HIV and AIDS at Pitt. "We hope that the antibodies we have discovered will contribute to that triumph."
-end-
Additional co-lead authors of this research are Xianglei Liu, M.D., Ph.D., of Pitt; Alexandra Schäfer, Ph.D., and David R. Martinez, Ph.D., both of the University of North Carolina at Chapel Hill; and Swarali S. Kulkarni, M.Sc., of the University of Saskatchewan. Additional authors are Chuan Chen, Ph.D., Zehua Sun, Ph.D., Liyoung Zhang, Ph.D., all of Pitt; Sarah R. Leist, Ph.D., of the University of North Carolina at Chapel Hill; Aleksandra Drelich, Ph.D., of the University of Texas Medical Branch; Marcin L. Ura, Ph.D., and Eric Peterson, M.S., both of Abound Bio; and Alison Berezuk, Ph.D., Sagar Chittori, Ph.D., Karoline Leopold, Ph.D., Dhiraj Mannar, B.Sc., Shanti S. Srivastava, Ph.D., and Xing Zhu, Ph.D., all of the University of British Columbia.

This research was funded by National Institutes of Health grants F32 AI152296, T32 AI007151, AI132178, AI108197 and P30CA016086, as well as UPMC; the Burroughs Wellcome Fund; a Canada Excellence Research Chair Award; Genome BC, Canada; Canadian Institutes for Health Research; and Canadian Foundation for Innovation.

To read this release online or share it, visit https://www.upmc.com/media/news/091420-mellors-dimitrov-covid-ab8.

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.

About UPMC

A $21 billion health care provider and insurer, Pittsburgh-based UPMC is inventing new models of patient-centered, cost-effective, accountable care. The largest nongovernmental employer in Pennsylvania, UPMC integrates more than 90,000 employees, 40 hospitals, 700 doctors' offices and outpatient sites, and a 3.9 million-member Insurance Services Division, the largest medical insurer in western Pennsylvania. In the most recent fiscal year, UPMC contributed $1.4 billion in benefits to its communities, including more care to the region's most vulnerable citizens than any other health care institution, and paid more than $800 million in federal, state, and local taxes. Working in close collaboration with the University of Pittsburgh Schools of the Health Sciences, UPMC shares its clinical, managerial, and technological skills worldwide through its innovation and commercialization arm, UPMC Enterprises, and through UPMC International. U.S. News & World Report consistently ranks UPMC Presbyterian Shadyside among the nation's best hospitals in many specialties and ranks UPMC Children's Hospital of Pittsburgh on its Honor Roll of America's Best Children's Hospitals. For more information, go to UPMC.com.

http://www.upmc.com/media

University of Pittsburgh

Related Infectious Diseases Articles:

COVID-19 a reminder of the challenge of emerging infectious diseases
The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC).
Certain antidepressants could provide treatment for multiple infectious diseases
Some antidepressants could potentially be used to treat a wide range of diseases caused by bacteria living within cells, according to work by researchers in the Virginia Commonwealth University School of Medicine and collaborators at other institutions.
Opioid epidemic is increasing rates of some infectious diseases
The US faces a public health crisis as the opioid epidemic fuels growing rates of certain infectious diseases, including HIV/AIDS, hepatitis, heart infections, and skin and soft tissue infections.
Infectious diseases could be diagnosed with smartphones in sub-Saharan Africa
A new Imperial-led review has outlined how health workers could use existing phones to predict and curb the spread of infectious diseases.
The Lancet Infectious Diseases: Experts warn of a surge in vector-borne diseases as humanitarian crisis in Venezuela worsens
The ongoing humanitarian crisis in Venezuela is accelerating the re-emergence of vector-borne diseases such as malaria, Chagas disease, dengue, and Zika virus, and threatens to jeopardize public health gains in the country over the past two decades, warn leading public health experts.
Glow-in-the-dark paper as a rapid test for infectious diseases
Researchers from Eindhoven University of Technology (The Netherlands) and Keio University (Japan) present a practicable and reliable way to test for infectious diseases.
Math shows how human behavior spreads infectious diseases
Mathematics can help public health workers better understand and influence human behaviors that lead to the spread of infectious disease, according to a study from the University of Waterloo.
Many Americans say infectious and emerging diseases in other countries will threaten the US
An overwhelming majority of Americans (95%) think infectious and emerging diseases facing other countries will pose a 'major' or 'minor' threat to the U.S. in the next few years, but more than half (61%) say they are confident the federal government can prevent a major infectious disease outbreak in the US, according to a new national public opinion survey commissioned by Research!America and the American Society for Microbiology.
Decline in deaths from most infectious diseases in US, large differences among counties
Deaths due to most infectious diseases decreased in the United States from 1980 to 2014, although there were large differences among counties.
AI to fight the spread of infectious diseases
Public outreach campaigns can prevent the spread of devastating yet treatable diseases such as tuberculosis (TB), malaria and gonorrhea.
More Infectious Diseases News and Infectious Diseases Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.