In this interview, News-Medical talks to Dr. Natalia Freund about her latest research on COVID-19, and how most people are able to make neutral antibodies against the virus .
What prompted your research on the COVID-19 pandemic?
When the pandemic hit Israel, all aspects of our lives have changed, so like many other laboratories we had to put forward ongoing projects and focus on the new virus. .
In fact, we have been developing tools and platforms for antibody detection and isolation for a long time, while focusing on other infectious diseases such as HIV-1 and tuberculosis, and we were so prepared and we can put our devices into the new COVID-19 problem.
So, at the beginning of March, we started collaborating with two hospitals in Israel, the Ichilov Center and the Kaplan Centers where COVID-19 patients were listed and began studying natural antibody responses in humans. were infected with SARS-CoV-2 while dealing with questions such as what antibodies are excreted in infected people, what is the interaction between disease depth and the immune response, and what level of immunity prevents re-infection.
SARS-CoV-2. Image credit: Cristian Moga / Shutterstock.com
What is the neutralization of antibodies and how do these differ from other types of antibodies?
Protein antibodies are made by cells of our immune system called B cells. They are released when they are infected or vaccinated, and are particularly specific to the disease. in which they do.
Neutral antibodies are a specific subtype of antibodies that can physically prevent the virus from entering the cell and reproducing. This is done by attaching an antibody to “weak spots” within the virus, and it is the binding itself that stops the virus from progressing through its life cycle.
Levels of these antibodies vary from person to person, but once they are secreted, even when their levels decay, immunological memory is maintained and can be these antibodies are easily reabsorbed when they appear the latter.
Can you tell me how you did your most recent research? What did you find?
Our main goal was to understand whether people infected with SARS CoV-2 develop neutral antibodies and against what targets the virus. In addition, we asked what the relationship is between the antibody responses and the severity of the disease.
Initially, we thought that higher levels of neutralizing antibodies are associated with a lack of severe infection, but we found the opposite: it turns out that people with neutralizing antibodies have fewer neutralizing antibodies. very mild disease compared with those with severe symptoms.
We now understand that, during a very severe infection, the patient has many viruses and this stimulates his immune response to produce more neutral antibodies, as opposed to an asymptomatic disease where the infection can be being a little “invisible” to the immune system.
Antibodies attack SARS-CoV-2 virus. Image credit: Kateryna Kon / Shutterstock.com
What is antibody antibody therapy and how do your results also support the use of this for the prevention and treatment of COVID-19?
Combination antibody therapy combines monoclonal antibodies that bind various “weak spots” on the virus so they can block the virus in several places. The idea of cocktail drugs was first used in HIV-1 treatment when clinicians realized that only one drug led to a rapid viral escape when the virus mutated in the specific area where the drug at hits.
On the other hand, attacking several sites simultaneously reduces the chances of “escape mutants” to near zero, making treatment very effective. Antibody combination therapy relies on a similar concept; using just one antibody allows the virus to escape by making just one mutation, and when using two or even three monoclonal antibodies together the virus needs about two or three different sites damaged at the same time, which is impossible. However, in order to neutralize such compounds of antibodies one must find antibodies that target different sites of the virus.
Fortunately, using our tools and with the help of our colleagues in Israel and the US who tested the antibodies we set aside for neutralization, we were able to find many different types of neutralizing antibodies. in our patients. Finally, we focused on three main families of antibody-neutralizing. When we mixed these antibodies together we found a very effective inhibition of the virus in culture over several days.
In addition to vaccines, why is it important for clinicians to have specific anti – SARS-CoV-2 medications?
An antibody cocktail is what we call a tolerant vaccine. Although active vaccines are given to healthy people and their purpose is to induce the body to produce neutral antibodies and a protective memory to protect against future exposures, it is a tolerant vaccine when we provide the immune response from the outside, as a drug.
Even now with the incredible vaccination efforts around the world, we still have diseases and hospitals caused by hard COVID-19. Also, some people have immunodeficiencies or immune suppression and it is unclear whether they can make specific antibodies after receiving the vaccine.
Therefore, it is important to equip clinicians with weapons against this virus. Monoclonal antibodies have proven highly effective biological drugs with minimal side effects, and can be used to treat a person with high viral loads to prevent serious infection.
How was bioinformatics used in your research?
Our lab is called a “wet lab” so we were very lucky to have strong computational partners to do this part. As soon as we identified neutral antibodies in our group of convalescent donors, and were able to identify their genetic footprints, we detected these footprints in healthy, unprotected donor samples. was collected before COVID-19 broke into our consciousness.
Using bioinformatics tools we were able to identify the precursors for neutralizing anti-COVID-19 antibodies in almost all healthy donors. This is very good news because when they receive a vaccine or an infection almost everyone means to produce these neutral antibodies, which will protect the vaccinated / infected person in the future.
The concept of bioinformatics. Image credit: CI Photos / Shutterstock.com
Do you believe your research will help us understand SARS-CoV-2 and our body’s immune responses to this virus?
I have to admit that, in the past year, I was skeptical about SARS-CoV-2; on the one hand this year there have been major economic, personal and social challenges. On the other hand, we have all seen science unique in its glory.
A year ago, we knew so little about this virus, and look, we now have four approved vaccines that are given to millions, and several tens of drugs in clinical trials. Many laboratories around the world, including my former consultant Michel Nussenzweig, have done amazing work on antibodies and vaccines.
In this context, I feel that our work responds well to this broad movement of discovery that will help to end this pandemic and prepare more. best for future ones.
What are the next steps for your research?
Well, first we are still looking for pharma partners to take our antibodies to the next clinical stage, for testing in humans. We will also continue to collaborate with vaccine centers in Israel to try to understand the longevity of antibody responses after infection and vaccination, and we will seek to understand how the neutralizing antibodies found in it. the vaccines and infectious people perform against the new versions of SARS-CoV-2.
We need to remember that this is an ongoing race, and while we will make progress in the prevention and treatment of COVID-19, the growing virus will try to overcome our efforts. To win this race we need to keep a close eye on the new versions as we continue to develop new anti – virus strategies.
Where can readers find out more?
Labs website: http://www3.tau.ac.il/nfreund/
About Dr. Natalia Freund
Dr. Natalia Freund specializes in antibody responses to infectious diseases. Natalia has completed a Ph.D. from the Faculty of Life Sciences at Tel Aviv University’s Department of Cell Research and Immunology with a focus on the first SARS Coronavirus. She then moved to Rockefeller University in New York City as part of her postdoc, where she studied antibody responses to HIV-1 in infected people.
In 2017, she entered Tel Aviv University’s Sackler School of Medicine as an Associate Professor and faculty member. In TAU she continues to use single-cell methods to study human antibody response during infection. She has presented a number of donations and awards, such as the Clore Doctoral Fellowship, the TAU Breaking Award, and Israeli Science Foundation grants.