• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
Friday, September 22, 2023
BIOENGINEER.ORG
No Result
View All Result
  • Login
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Cancer

Demonstration of a potent, universal coronavirus monoclonal antibody therapy for all COVID-19 variants

Bioengineer by Bioengineer
July 21, 2022
in Cancer
Reading Time: 6 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

BIRMINGHAM, Ala. – The SARS-CoV-2 that causes COVID-19 has killed 6.3 million people worldwide since 2019, painfully highlighting the vulnerability of humanity to novel coronaviruses.

James Kobie

Credit: UAB

BIRMINGHAM, Ala. – The SARS-CoV-2 that causes COVID-19 has killed 6.3 million people worldwide since 2019, painfully highlighting the vulnerability of humanity to novel coronaviruses.

Researchers discovered a neutralizing monoclonal antibody that potentially acts as a potent universal coronavirus therapy against SARS-CoV-2 and all its variants of concern, including Beta, Gamma, Delta, Epsilon and Omicron. It also shows effectiveness against the deadly previous coronaviruses SARS-CoV, the Severe Acute Respiratory Syndrome that emerged in China in 2002, and MERS-CoV, the Middle East Respiratory Syndrome that appeared in Saudi Arabia in 2012. It even shows effectiveness against several common cold coronaviruses.

This universal activity against all beta-coronaviruses results from a monoclonal antibody targeting the S2 stalk region of the viral spike (S) protein that is highly conserved among beta-coronaviruses, yet is also essential for the virus to attach and enter cells, leading to infection.

In animal experiments, the monoclonal antibody protected against infections when given as an intraperitoneal injection or a nasal dose. The study is published in the journal PLOS Pathogens by co-senior authors James J. Kobie, Ph.D., and Mark R. Walter, Ph.D., of the University of Alabama at Birmingham, and Luis Martinez-Sobrido, Ph.D., of the Texas Biomedical Research Institute, San Antonio, Texas.

The monoclonal antibody, and another monoclonal antibody discovered earlier by the researchers, are being developed as a therapeutic cocktail for COVID-19 under license to Aridis Pharmaceuticals, a California biopharmaceutical company.

The overall goal of researchers at UAB, Texas Biomedical Research Institute and Aridis is to find antibodies that do not permit immune escape by mutated variants of SARS-CoV-2, the virus that causes COVID-19. This includes Omicron and any future variants of concern. It is hoped that identifying and studying such antibodies can lead to the development of vaccines that protect from all coronaviruses.

“SARS-CoV-2 marks the third time in the last two decades a beta-coronavirus has caused significant mortality in humans,” Kobie said. “SARS-CoV-2 has caused the most infections and deaths worldwide. New variants pose the risk of evading the immune system — even in vaccinated and previously infected individuals — and there remains the potential for other genetically distinct coronaviruses to emerge as new pandemic strains in the future.”

“For these reasons, finding new therapeutic and prophylactic drugs and vaccine strategies that have universal activity against the coronavirus is essential for protecting humanity against the current and future beta-coronavirus outbreaks or pandemics.”

Vaccines and other monoclonal antibodies against SARS-CoV-2 have largely focused on the receptor-binding domain, or the RBD, located at the heads of the S viral protein spike that projects from the surface of the virus. Each virus has 24 to 40 spikes. The RBD is very good at eliciting an immune response, but that portion of the S permits many mutations that can let the virus escape antibodies.

One key in the present research was finding an antibody target on a part of the spike called the S2, or the stalk region. This region is highly conserved and only rarely mutates because that would disrupt its essential function. After the RBD at the head of the S attaches the coronavirus to a receptor molecule on the surface of a target cell, the S2 stalk acts to bring the virus inside the target cell. There the virus replicates, killing the cell and releasing a hoard of new, infectious virions.

The hunt for useful antibodies began with screening blood samples from adult convalescent patients at UAB Hospital through the UAB COVID Enterprise Biorepository led by Paul Goepfert, M.D., and Nathaniel Erdmann, M.D., Ph.D., UAB Division of Infectious Diseases. Memory B cells in the blood that bound to custom S2 protein baits, developed by Walter to mimic the natural state of the S2 domain of spike, were used to create a panel of unique cells able to produce human monoclonal antibodies, or hmAbs, which then could be screened for effectiveness against the virus. Memory cells targeting S2 are scarce because the RBD is immunodominant; its several antigenic sites account for 90 percent of the neutralizing activity of convalescent plasma.

Seventeen hmAbs showed binding to the S2 protein. Only four of these were able to neutralize a SARS-CoV-2 pseudovirus and a live SARS-CoV-2, including the Beta and Omicron variants.

The top performer, the 1249A8 hmAb, had the broadest and most potent neutralizing activity, against strains that included the original Wuhan, China, SARS-CoV-2; the Beta, Gamma, Delta, Epsilon and Omicron variants; the SARS-CoV and MERS-CoV; and two common cold viruses.

The hmAb protected mice from SARS-CoV-2 illness, as measured by maintenance of body weight and clearance of virus from mouse lungs four days after infection. Furthermore, the 1249A8 hmAb showed synergism when used in combination with 1213H7, another hmAb discovered by the researchers. 1213H7 is active against the RBD of the viral S glycoprotein.

In collaboration with Aridis, which specializes in the respiratory delivery of monoclonal antibodies to treat infections, the researchers had previously demonstrated that direct respiratory delivery of a SARS-CoV-2 RBD-specific 1213H7 hmAb enables substantial dose-sparing therapeutic activity in hamsters. The researchers thus evaluated this delivery mechanism for the treatment of SARS-CoV-2 and SARS-CoV with the S2-specific 1249A8 hmAb and the 1213H7 hmAb.

The 1249A8, 1213H7 cocktail — given as a nasal dose, 12 hours after infections with SARS-CoV-2 Delta or the first SARS-CoV isolated in 2002 — had broad therapeutic activity in hamsters.

“These results indicate in vivo cooperativity between S1- and S2-specific neutralizing hmAbs and that potent universal coronavirus neutralizing mAbs with therapeutic potential can be induced in humans and can guide universal coronavirus vaccine development,” Kobie said. “Numerous SARS-CoV-2 RBD-specific hmAbs have been approved for clinical use. Unfortunately, several have become irrelevant with their inability to neutralize variants of concern, including the most recent Omicron, highlighting the perilous future of RBD-only based mAb therapeutics against coronaviruses.”

Aridis is using the two hmAbs in its AR-701 cocktail designed for inhaled delivery. AR-701 is engineered for long-acting effectiveness, potentially lasting a year or more when used in humans.

Kobie is an associate professor in the UAB Department of Medicine, Division of Infectious Diseases, and Walter is a professor in the UAB Department of Microbiology. Both departments are in the Marnix E. Heersink School of Medicine at UAB.

Co-first authors of the paper, “Potent universal-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody,” are Michael S. Piepenbrink, UAB Department of Medicine, Division of Infectious Diseases, and Jun-Gyu Park, Texas Biomedical Research Institute.

Co-authors besides Kobie, Walter, Martinez-Sobrido, Piepenbrink, Park, Erdmann and Goepfert are Madhubanti Basu and Sanghita Sarkar, UAB Department of Medicine, Division of Infectious Diseases; Chengjin Ye and Ahmed Magdy Khalil, Texas Biomedical Research Institute; Ashlesha Desphande, UAB Department of Microbiology; Andreas Loos, David Chauvin, Jennifer Woo, Philip Lovalenti and Vu L. Truong, Aridis Pharmaceuticals, Los Gatos, California; and Richard A. Bowen, Colorado State University, Fort Collins, Colorado.

Funding came from National Institutes of Health grant R01 AI161175, National Institute of Allergy and Infectious Diseases contract 75N93021C00014, UAB, the Texas Biomedical Research Institute, and Aridis Pharmaceuticals.

In declarations of interest, Michael S. Piepenbrink, Jun-Gyu Park, Ashlesha Desphande, Fatai S. Oladunni, Madhubanti Basu, Sanghita Sarkar, Nathaniel B. Erdmann, Paul A. Goepfert, Mark R. Walter, Luis Martinez-Sobrido and James J. Kobie are co-inventors on patents that include claims related to the hmAbs described. Andreas Loos, David Chauvin, Jennifer Woo, Philip Lovalenti and Vu L. Truong are employees of Aridis Pharmaceuticals.



Journal

PLoS Pathogens

DOI

10.1371/journal.ppat.1010691

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody

Article Publication Date

21-Jul-2022

COI Statement

In declarations of interest, Michael S. Piepenbrink, Jun-Gyu Park, Ashlesha Desphande, Fatai S. Oladunni, Madhubanti Basu, Sanghita Sarkar, Nathaniel B. Erdmann, Paul A. Goepfert, Mark R. Walter, Luis Martinez-Sobrido and James J. Kobie are co-inventors on patents that include claims related to the hmAbs described. Andreas Loos, David Chauvin, Jennifer Woo, Philip Lovalenti and Vu L. Truong are employees of Aridis Pharmaceuticals.

Share12Tweet8Share2ShareShareShare2

Related Posts

Immune Cells

Australian research leads to clinical trial for rare women’s cancers

September 22, 2023
Annika Wylie

Cancer Prevention and Research Institute of Texas awards $2 million grant to SMU

September 21, 2023

Rewiring tumor mitochondria enhances the immune system’s ability to recognize and fight cancer

September 21, 2023

Combination of cancer vaccine and T cell therapy benefits patients with advanced ovarian cancer

September 21, 2023

POPULAR NEWS

  • blank

    Microbe Computers

    58 shares
    Share 23 Tweet 15
  • University of South Florida scientist: Barnacles may help reveal location of lost Malaysia Airlines flight MH370

    46 shares
    Share 18 Tweet 12
  • Lithuanian invention at the forefront of solar technology breakthrough

    41 shares
    Share 16 Tweet 10
  • A pioneering study from Politecnico di Milano sheds light on one of the still poorly understood aspects of cancer

    34 shares
    Share 14 Tweet 9

About

We bring you the latest biotechnology news from best research centers and universities around the world. Check our website.

Follow us

Recent News

One-stop implementation from signal detection to processing

Australian research leads to clinical trial for rare women’s cancers

Ochsner offers tuition assistance to aspiring nurses and doctors

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 57 other subscribers
  • Contact Us

Bioengineer.org © Copyright 2023 All Rights Reserved.

No Result
View All Result
  • Homepages
    • Home Page 1
    • Home Page 2
  • News
  • National
  • Business
  • Health
  • Lifestyle
  • Science

Bioengineer.org © Copyright 2023 All Rights Reserved.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In