Christopher Barnes, a postdoctoral student at Caltech, is one of those studies. In the lab of Pamela Bjorkman, professor of Biology and Biological Engineering David Baltimore, Barnes studies how the human body produces immune cells and specialized proteins called antibodies that can fight the countless other strains of HIV. However, for the past few months, he has been leading the lab’s COVID-19 study team and refocusing the techniques used to examine HIV in the new coronavirus, severe Acute Respiratory Syndrome 2 coronavirus (SARS-CoV-2).
Now Barnes and his team have captured the first photographs of antibodies, purified of the blood plasma of others who have recovered from COVID-19, attached to a key protein in the SARS-CoV-2 virus. In addition, the visualization of an exemplary antibody that interacts with this protein allowed the team to identify sites on the surface of the virus that are vulnerable to attacks through the immune system. An article describing these studies will be published in Cell magazine and will now be available online.
A detailed portrait of antibodies and viruses
The human framework can produce countless antibodies, specialized proteins that attack and neutralize viruses or other pathogens. Just as a football player can use many tactics to protect himself against an opposing player, an anti-frame can try to block a virus in other ways. Some, however, are more effective than others. When an anti-frame well causes a virus to fail to infect cells, it is called “neutralization”.
Barnes and Bjorkman are for antibody variants that can be “broadly neutralizing”. In other words, they are for effective antibodies that oppose many variants of a type of virus, or in the case of SARS-CoV-2, which does not vary as much as HIV, very resistant neutralizing antibodies.
The team worked with long-standing collaborators at Rockefeller University in New York, which is a major site of the COVID-19 epidemic in the United States. Michel Nussenzweig’s laboratory, led by study associate Davide Robbiani, took blood samples from others who had recovered from COVID-19. Upon receiving these plasmas, Barnes and his colleagues sought to isolate the unique aggregate of antibodies in each person’s samples to locate which antibodies were most productive in combating SARS-CoV-2.
To see where the coronavirus might be vulnerable, it’s helpful to see what the virus looks like and how it triggers infections. Each SARS-CoV-2 virus has giant structures of spiny proteins on its surface that give it a crown appearance, hence the so-called “coronavirus” (“crown” is the Latin word for crown). A virus uses its so-called complex protein (S) as a prey to cling to a human mobile and begin its invasion of that mobile. An antibody capable of blocking protein S would be very effective in preventing the virus from infecting mobiles.
Antibodies can bind to many other regions, or epitopes, of the S protein, leading to more or less significant neutralization of the virus. By analogy, if you need to prevent a venomous snake from biting it, you can hold it by the tail, which would allow the snake to hit it, or you can simply catch it near the head, thus reducing your chances of being bitten. .
To find out which epitopes were the main targets of antibody reactions, Barnes and his team took detailed photographs of patients’ purified antibodies when interacting with the SARS-CoV-2 S protein. The researchers found that the patient’s antibodies were connected to two distinct regions of the S protein, adding one region, the receptor binding domain (RBD), which is the protein’s ability to bind to the host cell.
“As far as we know, this is the first time a team has designed an aggregate of purified human blood antibodies after a viral infection to visualize the targets of those antibodies circulating in the recovered individual,” Barnes explains.
Barnes then targeted a specific type of antibody that showed great ability to neutralize the virus. First he purified a complex composed of viral protein S and similar antibody, then used a strategy called single particle cryoelectronic microscopy to take photographs of tangled entities, a procedure similar to imaging a complete diversity while being able to get the precise locations of each grain of sand.
The RBD S protein can adopt two other orientations, called “high” and “low” conformations. Barnes and his colleagues received the first high-resolution photographs of an antibody neutralizing SARS-CoV-2 connected to RBD in its “upstream” shaping.
Barnes discovered that the neutralizing antibody adheres to the RBD S protein in a position that extends to both sides of the RBD component that would be fixed to a host cell; In this way, the antibody prevents the protein S from infecting cells and neutralizes the virus.
“Painted vaccines giving the user a part of a pathogen and thus inducing the frame to produce antibodies opposed to this pathogen, so that no long-term infection can be established. Therefore, a vaccine will need to be designed in particular to inspire the human framework to produce the most effective types of antibodies possible,” Explains Barnes. “Knowing which regions of the SARS-CoV-2 virus are most vulnerable to antibodies is vital in vaccine design. And knowing which categories of antibodies are of maximum effectiveness can help us design better antiframe therapies.”
“One thing that is particularly appealing about Christopher’s design is that it shows that the antiframe, although highly neutralizing, has not evolved for optimal binding to the SARS-CoV-2 S protein,” Bjorkman explains. “This suggests that these types of antibodies may not be difficult to induce in a person’s body with a vaccine. In addition, this suggests that the use of protein engineering techniques to improve these antibodies for healing purposes deserves to be conceivable.”
The intersection of science and scientists
The COVID-19 pandemic has given urgency to this research, but work, like all clinical companies, is not positioned in the vacuum, away from other occasions occurring in the world; nor scientists can absolutely separate themselves from their experiments, intelligent and bad, internal and external from the lab. In fact, at the time the team article accepted for publication, there was another serious challenge in the minds of many researchers, adding Barnes and his colleagues. On May 25, George Floyd’s death at the hands of Minneapolis police sparked national protests against police brutality and systemic racism. For Barnes, it’s a misleading reminder of his own struggles opposed to the racism he faced in the world and in academia.
“Someday I’ll tweet about my paintings,” Barnes wrote on his Twitter account days after Floyd’s death. “But I chose to tweet about George Floyd, Ahmaud Arbery [a black guy shot dead in February] and all the other brothers we lost without explanation. #BlackLivesMatter.”
“I’m a scientist. I’m a black scientist. I’ve been on school campuses since 2004, and I’m the only African-American scientist in my entire building. Until I arrived at Caltech, I never had a Mentor I could pass to communicate about science, race and culture,” Barnes says. “It’s a difficult area to navigate when you have to compartmentalize your person as a person, compartmentalize your emotions. We can’t just rent other people of color and then tell them to leave their culture, reports and humanity at the door. These existing occasions are the best representation of this duality: to have to show joy and enthusiasm to my colleagues for the publication of our article, while I suffer from pain and sadness within the constant reminder of racist society in which other blacks we will have to exist. . “
“Academics, like the united States, are tainted by the racist scheme that underlies everything in our society. As black scientists, all our experiments are affected and we bring this burden and the daily jobs that are expected in our positions. This top point as a black scientist calls for exceptional work, exemplified through the work of Dr. Barnes,” says Bil Clemons, professor of biochemistry at Caltech and, like Barnes, also a structural biologist. Mentor Clemons Barnes when he arrived at Caltech. In addition to leading his own group, Clemons chairs the President’s Diversity Council at Caltech. “Dr. Barnes’ HIV studies are in a position to show that he is in a position for a professorship. His immediate progress in COVID-19 studies, in the face of all our social problems, shows that he will be a leader in the next generation of academics.”
A few days after Floyd’s death, Caltech’s Center for Inclusion – Diversity (CCID) organized a virtual panel in which members of Caltech’s African-American and black network (students, universities, and staff) shared some of their reports with an audience of approximately 1,000 members of the wider Caltech network. Clemons and Barnes didn’t participate either. This is the first in a series of systems and conversations through which the Caltech network will talk and evaluate the climate of inclusion.
“Sharing my story is a vital first step in starting conversations with my peers, complicated conversations that I hope will continue over the years,” Barnes says.
Cindy Weinstein, Director of Diversity at Caltech, says: “Membership is the foundation of happiness, creativity and productivity. On this basis, Americans and communities can succeed to their full potential; without it, they can’t. Caltech is committed to equity, inclusion and diversity and recognizes that these are the pillars on which the club is lived, built and sustained.”
In fact, in a note to the Caltech network on July 6, the President and the Academic Directorate of Caltech provided an update on the new steps the Institute will take “so that we continually believe and reaffirm a campus where it is clear, in everything we do, that black life is important, that black minds matter. Agreement “that includes greater investments and systems to build the flow of students, postdoctoral fellows and colored universities.
“We try to give an example of how a diverse and inclusive community, committed to equity, allows Americans to thrive in fulfilling the Institute’s leading curriculum and education project,” the memo says.