LA JOLLA—The National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health, has awarded more than $6.4 million to Erica Ollmann Saphire, Ph.D., professor at La Jolla Institute for Immunology (LJI), to support research toward COVID-19 antibody therapeutics. The Coronavirus Immunotherapeutic Consortium (CoVIC) is now partnered with NIAID to provide independent evaluation of antibody therapeutics as part of the federal government’s Operation Warp Speed. The funding to LJI will fuel ongoing efforts by CoVIC, led by Saphire, to analyze virus-fighting antibodies and track how the novel coronavirus may attempt to escape those antibodies.
“Most COVID-19 antibody discovery efforts focus on one half of antibody molecules—the part that anchors to SARS-CoV-2, the virus that causes COVID-19. This funding allows us to collect information about the other half of the antibody—the part that signals to the rest of the immune system the presence of the virus,” says Saphire. “New data suggest that the ability of that half to signal for immune help separates survivable cases from fatal cases of viral infection. By considering both halves of the antibody, we can gain a more complete picture of how antibodies against SARS-CoV-2 work best, and we can better choose the ones that will be most effective as therapeutics.”
CoVIC was established in March 2020 through funding from the COVID-19 Therapeutics Accelerator, a partnership between the Bill & Melinda Gates Foundation, Wellcome and the Mastercard Impact Fund. Through CoVIC, Saphire’s lab is fielding promising therapeutic antibody candidates against COVID-19—contributed by dozens of laboratories around the world—for side-by-side, apples-to-apples comparisons of antibody function. As part of CoVIC analyses, her team uses LJI’s powerful pair of Titan electron microscopes for high-resolution analysis of how the antibodies interact with proteins of SARS-CoV-2.
“CoVIC research provides a framework by which therapeutics can be compared on an even playing field,” says Sharon Schendel, Ph.D., program manager for the CoVIC in the Saphire Lab at LJI.
The CoVIC has received additional funding from NIAID as a supplement to Saphire’s U19 program, a Center of Excellence in Translational Research, and will support five key CoVIC projects:
- LJI Professor Sujan Shresta, Ph.D., will use novel models to evaluate interactions of therapeutic antibodies against SARS-CoV-2 with human receptors to understand a phenomenon called antibody-dependent enhancement (ADE), which could make some COVID-19 cases worse. Her work could reveal whether ADE is a risk at all.
- LJI Professor Bjoern Peters, Ph.D., will double the size of the CoVIC Database, a searchable catalog of antibodies that provides interactive analysis tools to compare CoVIC antibodies.
- Bette Korber, PhD., of Los Alamos National Laboratory, will continue to track SARS-CoV-2 mutations as they arise to determine if any can escape neutralization by antibody therapeutics.
- Researchers at the Ragon Institute, led by Galit Alter, Ph.D., and the University of Texas Medical Branch at Galveston, led by Alex Burkreyev, Ph.D., will analyze how the Fc region of antibodies can protect against the virus, and LJI’s Shresta will also evaluate protection in a mouse model that better mimics a key human Fc receptor.
- At the University of Wisconsin, researchers Yoshihiro Kawaoka, Ph.D., and Peter Halfmann, Ph.D., will study which sites on the virus are vulnerable to mutation and which therapeutics are more resistant.
For each study, researchers will analyze a group of “blinded” antibodies, meaning the scientists will not know which labs supplied the antibodies. Blind testing allows for objective analysis of which antibodies hold promise against SARS-CoV-2. This approach is modeled after the success of the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC), a groundbreaking initiative launched by Saphire to pursue therapies and vaccines for hemorrhagic fever viruses such as Ebola.
Saphire explains that the CoVIC is an effective way for U.S. government scientists to seek independent and standardized analysis of promising clinical candidates.
“The CoVIC provides an even platform for nonprofits, small biotechs and multinational corporations alike to accelerate their therapeutic candidates with complete and independent evaluation,” says Saphire. “CoVIC will also identify and mobilize antibody therapies to impoverished people around the world. The virus will return here again and again unless we can achieve global immune protection. No one is safe until everyone is safe.”
The funding is a supplement to NIAID grant U19AI142790-02.
