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Finding Antibodies that Neutralize SARS-CoV-2

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Neutralizing Antibodies
Caption: Model of three neutralizing antibodies (blue, purple and orange) bound to the spike protein, which allows SARS-CoV-2 attach to our cells. Credit: Christopher Barnes and Pamela Bjorkman, California Institute of Technology, Pasadena.

It’s now clear that nearly everyone who recovers from coronavirus disease 2019 (COVID-19) produces antibodies that specifically target SARS-CoV-2, the novel coronavirus that causes the infection. Yet many critical questions remain. A major one is: just how well do those particular antibodies neutralize the virus to fight off the infection and help someone recover from COVID-19? Fortunately, most people get better—but should the typical antibody response take the credit?

A new NIH-funded study of nearly 150 people who recovered from COVID-19 offers some essential insight. The study, published in the journal Nature, shows that most people, in fact, do produce antibodies that can effectively neutralize SARS-CoV-2. But there is a catch: 99 percent of the study’s participants didn’t make enough neutralizing antibodies to mount an ideal immune response.

The good news is that when researchers looked at individuals who mounted a strong immune response, they were able to identify three antibodies (depicted above) that were extremely effective at neutralizing SARS-CoV-2. By mass-producing copies of these antibodies as so-called monoclonal antibodies, the researchers can now better evaluate their potential as treatments to help people who don’t make strongly neutralizing antibodies, or not enough of them.

These findings come from a team led by Michel Nussenzweig, Paul Bieniasz, and Charles Rice at The Rockefeller University, New York, and Pamela Bjorkman at the California Institute of Technology, Pasadena. In the Nussenzweig lab, the team has spent years searching for broadly neutralizing antibodies against the human immunodeficiency virus (HIV). In response to the COVID-19 pandemic and its great urgency, Nussenzweig and team shifted their focus recently to look for promising antibodies against SARS-CoV-2.

Antibodies are blood proteins that the immune system makes to neutralize viruses or other foreign invaders. The immune system doesn’t make just one antibody to thwart an invader; it makes a whole family of antibodies. But not all antibodies in that family are created equal. They can vary widely in where they latch onto a virus like SARS-CoV-2, and that determines how effective each will be at blocking it from infecting human cells. That’s one reason why people respond differently to infections such as COVID-19.

In early April, Nussenzweig’s team began analyzing samples from volunteer survivors who visited The Rockefeller Hospital to donate plasma, which contains the antibodies. The volunteers had all recovered from mild-to-severe cases of COVID-19, showing their first signs of illness about 40 days prior to their first plasma collection.

Not surprisingly, all volunteers had produced antibodies in response to the virus. To test the strength of the antibodies, the researchers used a special assay that shows how effective each one is at blocking the virus from infecting human cells in lab dishes.

Overall, most of the plasma samples—118 of 149—showed at best poor to modest neutralizing activity. In about one-third of individuals, their plasma samples had below detectable levels of neutralizing activity. It’s possible those individuals just resolved the infection quickly, before more potent antibodies were produced.

More intriguing to the researchers were the results from two individuals that showed an unusually strong ability to neutralize SARS-CoV-2. Among these two “elite responders” and four other individuals, the researchers identified 40 different antibodies that could neutralize SARS-CoV-2. But again, not all antibodies are created equal. Three neutralized the virus even when present at extremely low levels, and they now will be studied further as possible monoclonal antibodies.

The team determined that those strongly neutralizing antibodies bind three distinct sites on the receptor-binding domain (RBD) of the coronavirus spike protein. This portion of the virus is important because it allows SARS-CoV-2 to bind and infect human cells. Importantly, when the researchers looked more closely at plasma samples with poor neutralizing ability, they found that they also contained those RBD-binding antibodies, just not in very large numbers.

These findings help not only to understand the immune response to COVID-19, they are also critical for vaccine design, revealing what a strong neutralizing antibody for SARS-CoV-2 should look like to help the immune system win. If a candidate vaccine can generate such strongly neutralizing antibodies, researchers will know that they are on the right track.

While this research showed that there’s a lot of variability in immune responses to SARS-CoV-2, it appears that most of us are inherently capable of producing antibodies to neutralize this devastating virus. That brings more reason for hope that the many vaccines now under study to elicit such neutralizing antibodies in sufficient numbers may afford us with much-needed immune protection.

Reference:

[1] Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Robbiani DF, Gaebler C, Muecksch F, et al. Nature. 2020 Jun 18. [Published online ahead of print].

Links:

Coronavirus (COVID-19) (NIH)

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)

Nussenzweig Lab (The Rockefeller University, New York)

Bjorkman Lab (California Institute of Technology, Pasadena)

NIH Support: National Institute of Allergy and Infectious Diseases

23 Comments

  • Andrew Goldstein says:

    Since SARS-CoV-2 primarily attacks cells in the respiratory mucosa, shouldn’t mucosal immunity, i.e., IgA antibodies, play an important role in attacking the virus?

    • Sajjan Das Paul says:

      Yes, you are right. The following site contains information about the importance of Immunoglobulin-A in COVID-19.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245198/#:~:text=Secretory%20IgA%20plays%20a%20crucial,of%20SARS%2DCoV%2D2.

      • Andrew Goldstein says:

        Thank you for the informative reply. It appears that antibody testing should include IgA detection.

        • Sajjan Das Paul says:

          Here it is written many times that not all patients produce antibodies to defend the disease. My question is, for those patients what are the defense mechanisms against the disease? Can you answer it?

          • Andrew Goldstein says:

            The human immune system’s defense mechanisms are complex. They include immediate or innate immunity, and adaptive or humoral (antibodies) immunity and cell mediated immunity. After almost 40 years of research, we still lack a clear understanding of an effective immune response to mucosal transmission of HIV. Thus, no vaccine despite rare but documented cases of women who acquire immunity to HIV. Lastly, we need to understand one’s genetic predisposition to infectious disease.

          • Sajjan Das Paul, Student, says:

            Genetic predisposition is impossible as this a totally new strain of Coronavirus. But, innate immunity, cell-mediated immunity and humoral immunity are of course possible. We have to go a long way for its detailed study. But as a student of Class X, I am much low-experienced and so it has become difficult for me to understand whether a vaccine is significant and whether this disease will be a dangerous endemic, as an Oxford University Professor says “Covid-19 not something to worry about, most of us don’t need vaccine.” …

  • james l says:

    If you would simply begin a dosage of supplemental Vitamin D at 3X normal daily doseage at the time blood is first drawn there will be a remarkable improvement in antibody production when second samples are drawn in 40 days with the variable of blood type determining the range with type O being the best and AB the worst and the others in an intermediate position. You seem to want to spend someone else’s money to test and test and test when the answer is simple and cheap and easily provable.

  • Heidy says:

    Then, it proves that the only people who might be benefiting from a vaccine against this virus are people with low immune system but not even, as the virus and immune system has many variables in the responses and most people produces antibodies in response to this virus.

  • Shams U says:

    Which medicicine is best for caronavirus pls tel.me detail

  • lizziedw says:

    But if people can make the neutralising antibodies why do we need a vaccine to make neutralising antibodies? I am so sick of constantly hearing about vaccines.

    • Al says:

      “But if people can make the neutralising antibodies why do we need a vaccine to make neutralising antibodies?”

      The people in this study endured an infection to produce their neutralizing antibodies. That is a natural response to any infection that gets above a critical threshold and sets off the adaptive immune response. It is a race against time as the virus replicates in the body and the immune system mobilizes many cell types to fight it off. The disease caused by this virus infection can result in very serious damage to the body’s organs and possibly death, so there is a price to pay to being infected naturally, surviving the infection (hopefully), and in the process the body has made antibodies.

      The vaccine is meant to simulate the infection to these cells and mobilize them, but without having the ability to truly infect the person and replicate, and therefore risking none of the disease complications in generating antibodies against a suitable target that will then in the future act against the real virus. It is essentially a deception of the immune system that treats it as an infection when it really isn’t. The whole concept of vaccines and why we use them is to confer immunity to deadly pathogens without having to suffer through actual infection by those pathogens and the diseases they cause. And if the vaccine is good, then in the future it will prevent that pathogen from ever infecting the person. That is what vaccines are.

  • Bill Lutin, MD,PhD says:

    The best treatment of an infectious disease is to prevent it in the first place. Neutralizing monoclonal antibodies, while useful to treat patients who are already ill, still allow patients to transmit the disease before they have symptoms. It’s significantly better not to get the illness at all, and safer for the general population.

  • ED says:

    Nice post! Thanks.

  • Bonieta Southers says:

    Since there are a number of younger individuals who have no symptoms, yet can pass the virus, has anyone looked into the reason for that? For example, that particular age group received the Hib vaccine. Perhaps those individuals have the mechanisms which recognize the CO-Vid virus, and attacks it. If we plan on creating a vaccine, perhaps we ought to take a look at some we have already used.

  • greenshirtman says:

    Are blood type o- in a better shape for covid19?
    I tested negative and my wife tested positive the same day.
    I have no symptoms but she does and it sucks
    I take daily vitamins, protein, coffee… I’m just a normal guy. My wife is A+
    She is been isolated for 5 days and has a fever of 101 sometimes.
    Covid19 sucks. I need to take the antibodies test because if I do come positive then I dont have we dont have to be isolated anymore.

  • Sajjan Das Paul says:

    Here it is written many times that not all patients produce antibodies to defend the disease. My question is, for those patients what are the defence mechanisms against the disease?

  • Mo younus says:

    i keep asking for this but no one has answered yet. There is a higher relation with AAT def. and severe Covid-19 patients then what is known. Why, because it’s misdiagnosed or most people don’t have symptoms. Versions of AAT alleles, AAT as TMPRSS-2 inhibitor and therapies used for AAT be reviewed and tested. It is known that AAT protein is up-regulated for severe Covid patients. The similarities between severe covid-19 patients and AAT is striking. I wish someone would look into this and say yay or nay. Thoughts?

    • Sajjan Das Paul, Student, says:

      Yes, in the case of TMPRSS-2, you are right. Actually you know that I am only in Class X and all these seem very much interesting to me, as well as new and difficult. But as far as I have researched TMPRSS-2 inhibitors can be used as candidate drugs against COVID-19 to prevent the priming of S protein of the virus. But, about the AAT def. disease I am not actually sure that whether COVID-19 involves “the degradation especially of lung tissue and eventually leads to characteristic manifestations of pulmonary emphysema” (Source:Wikipedia) just as AAT def. These were my thoughts regarding your comment. Any further opinion regarding this, feel free to comment here.

      • Mo younus says:

        Thank you Sajjan! There’s a lot of relation with low AAT protein a.k.a AAT def. and severe Covid-19. Look at how this protein keeps Neutrophil Elastase in check, reducing the buildup in the alveoli sacs. The more your research, it is more evident that AAT protein plays a role. Again, it would be great if AAT existing treatments can be tested on Covid-19 patients, TMPRSS-2 inhibitor role and checking versions of AAT allelles on Covid-19 patients.

        • Sajjan Das Paul, Student, says:

          Thank you very much! I don’t know whether TMPRSS-2 inhibiting drugs are given to COVID patients. Lots of sources are saying that COVID patients are tested with drugs like hydroxichloroquine, Remdisivir, Arsenicum album etc. But, to date I haven’t found any sources telling about TMPRSS-2 inhibitors. Moreover, the recent study suggesting airborne transmission as a dominant way of transmitting this virus made the scientists thinking …

  • Roseline G. says:

    Thanks for the information, there is a lot of information about COVID 19 we still don’t know. Thank for sharing.

  • Mehrunissa Jawed says:

    Thank you for sharing such great information.
    It has helped me in finding more detail about covid-19.

  • ciro leonardo pierri says:

    Thanks for the nice work. Any idea about why we did not start to prepare massive synthetic antibodies starting from the neutralizing ones directed against the RBD of SARS-CoV-1 spike protein, sharing with SARS-CoV-2 spike RBD more than 75% of identical residues??Might be that starting from that ones we can build a more specific antibody as described here: https://rdcu.be/b5rLj? any comment on this point?

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