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In this interview, News-Medical talks with Dr. Natalia Freund about her latest research on COVID-19 and how most people are capable of producing neutralizing antibodies against the virus.
What prompted your investigation into the ongoing COVID-19 pandemic?
When the pandemic hit Israel, all aspects of our lives changed and therefore, like many other labs, we had to suspend some ongoing projects and focus on the new virus.
In fact, we have been developing tools and platforms for antibody discovery and isolation for a long time, while focusing on other infectious diseases such as HIV-1 and tuberculosis, and were as prepared as possible to apply our tools to the new. COVID-19 problem.
So in early March, we started collaborating with two hospitals in Israel, the Ichilov Center and the Kaplan Centers, where COVID-19 patients were enrolled and we began investigating natural antibody responses in people who were infected with SARS-CoV. -2 while answering questions. such as what antibodies are produced in infected individuals, what is the interaction between the severity of the disease and the immune response, and what is the level of immunity that will prevent reinfection.
SARS-CoV-2. Image Credit: Cristian Moga / Shutterstock.com
What are neutralizing antibodies and how are they different from other types of antibodies?
Antibodies are proteins produced by cells of our immune system called B cells. They are produced by infection or vaccination, and are very specific to the disease against which they are produced.
Neutralizing antibodies are a specific subtype of antibodies that can physically block the virus from entering the cell and replicating. This is done by binding the antibody to “weak spots” within the virus, and it is the binding itself that prevents the virus from continuing its life cycle.
The levels of these antibodies vary from person to person, but once produced, even when their levels decrease, there is immune memory that is retained and these antibodies can easily be produced again after a second exposure.
Can you describe how you carried out your latest investigation? What did you discover?
Our main goal was to understand whether people who were infected with SARS CoV-2 develop neutralizing antibodies and against what targets of the virus. In addition, we asked what is the correlation between antibody responses and disease severity.
At first, we thought that higher levels of neutralizing antibodies are related to a lack of severe disease, but actually we found the opposite: It turns out that people with very mild disease have fewer neutralizing antibodies compared to those with severe symptoms.
We now understand that during severe illness, the patient has many viruses and this stimulates their immune response to produce more neutralizing antibodies, compared to an asymptomatic infection where the infection may be something “invisible” to the immune system.
Antibodies that attack the SARS-CoV-2 virus. Image Credit: Kateryna Kon / Shutterstock.com
What is antibody combination therapy and how do its results also support its use to prevent and treat COVID-19?
Antibody combination therapy consists of mixing monoclonal antibodies that bind to different “weak points” of the virus and thus can simultaneously block the virus in several places. The idea of a drug cocktail was first used in HIV-1 therapy when doctors realized that the use of a single drug resulted in rapid viral escape when the virus produced mutations in the specific place it was targeted. the drug was targeting.
On the other hand, attacking several sites at once reduces the chances of such “escape mutants” to almost zero, making the therapy very effective. Antibody combination therapy is based on a similar concept; the use of a single antibody allows the virus to escape by sometimes making only one mutation, whereas using two or even three monoclonal antibodies together requires the virus to simultaneously mutate two or three different sites at once, which is practically no it’s possible. However, to use such neutralizing antibody combinations, it is necessary to discover antibodies directed to different sites on the virus.
Fortunately, using our tools and with the help of our collaborators in Israel and the US who tested the antibodies we isolated for neutralization, we were able to find many different types of neutralizing antibodies in our patients. Finally, we focus on three main families of neutralizing antibodies. When we mixed these antibodies, we obtained extremely effective blocking of the virus in culture for several days.
Besides vaccines, why is it important for doctors to have specific treatments against SARS-CoV-2?
A cocktail of antibodies is what we call a passive vaccine. While an active vaccine is given to healthy people and its purpose is to induce the body to produce neutralizing antibodies and immune memory to protect itself from future exposures, a passive vaccine is when we provide the protective immune response from the outside, like a drug.
Even now, with the incredible vaccination efforts around the world, we still have infections and hospitalizations due to severe COVID-19. Also, some people have immunodeficiencies or immunosuppression and it is not clear if they can produce specific antibodies after vaccination.
Therefore, it is important to arm doctors with weapons against this virus. Monoclonal antibodies have proven to be extremely effective biological drugs with minimal side effects and can be used to treat a person with high viral loads to prevent severe manifestations of the disease.
How was bioinformatics used in your research?
Our lab is what is called a “wet lab,” so we were very lucky to have strong computational partners to do this part. Once we identified neutralizing antibodies in our convalescent donor cohort, and were able to recognize their genetic fingerprints, we went to look for these fingerprints in healthy and uninfected donor samples that were collected before COVID-19 broke into our consciousness.
Using bioinformatics tools we were able to identify the precursors of the neutralizing anti-COVID-19 antibodies in almost all healthy donors. This is very good news, as it means that after vaccination or infection almost everyone can produce these neutralizing antibodies, which will protect the vaccinated / infected person in the future.
Bioinformatics concept. Image Credit: CI Photos / Shutterstock.com
Do you think your research will help us better understand SARS-CoV-2 and our body’s immune responses to this virus?
I must admit that for the past year I have felt ambivalent about SARS-CoV-2; On the one hand, this year has posed enormous economic, personal and social challenges. On the other hand, we all witnessed outstanding science in all its splendor.
A year ago, we knew so little about this virus, and look, we now have four approved vaccines that are being administered to millions and several dozen drugs in clinical trials. Many labs around the world, including my former mentor Michel Nussenzweig, did incredible work on antibodies and vaccines.
In this context, I believe that our work fits perfectly into this general trend of discoveries that can help end this pandemic and better prepare for future ones.
What are the next steps for your research?
Well first we are still looking for pharmaceutical partners to take our antibodies to the next clinical stage, to test them in people. We are also continuing to collaborate with vaccine centers in Israel to try to understand the longevity of antibody responses after infection and vaccination, and we are trying to understand how neutralizing antibodies elicited in vaccinated and infected individuals behave against them. new variants of SARS-CoV-2.
We must remember that this is an ongoing race, and as we advance COVID-19 prevention and therapy, the virus evolves trying to outpace our efforts. To win this race we have to keep an eye out for new variants while we continue to develop new antiviral strategies.
Where can readers find more information?
Labs website: http://www3.tau.ac.il/nfreund/
About Dr. Amiga natalia
Dr. Natalia Freund specializes in antibody responses to infectious diseases. Natalia has completed her Ph.D. from the Faculty of Life Sciences at Tel Aviv University’s Department of Cell Research and Immunology, focusing on the first SARS coronavirus. He then moved to Rockefeller University in New York City as part of his postdoctoral fellowship, where he investigated antibody responses to HIV-1 in infected individuals.
In 2017, she joined Tel Aviv University’s Sackler School of Medicine as an assistant professor and faculty member. At TAU, he continues to apply single-celled methods to investigate the human antibody response during illness. She is the recipient of several scholarships and awards, such as the Clore Doctoral Fellowship, the TAU Breakthrough Prize, and the Israel Science Foundation Fellowships.
