Nearly three years into the pandemic, many of us now carry antibodies against the virus—due to an infection or two, a few doses of mRNA vaccine, or a round of monoclonal-antibody treatment. But not all immune responses are created equal, and how we first developed our antibodies may influence the character of our body’s response to SARS-CoV-2.
“Depending on the virus, feedback inhibition can either enhance immunity or inhibit it,” says Michel C. Nussenzweig, who co-led the study with colleagues Theodora Hatziioannou, Paul Bieniasz, and Marina Caskey. “Our results suggest that pre-existing SARS-CoV-2 antibodies can diversify the antibody response, which may increase the breadth of mRNA vaccines.”
Of guinea pigs and antibodies
Antibody feedback inhibition was first discovered at the turn of the century by pioneering epidemiologist Theobald Smith, who demonstrated that excess antibodies could inhibit the immune response to diphtheria in guinea pigs. It seemed like a curious twist—why would the same molecule that supposedly protects the animal from disease occasionally shut the immune system down?
We now know that viruses have multiple epitopes—stand-out bits of antigen that antibodies use to identify the virus and latch on to it. Once the body has produced strong antibodies for one epitope, the immune system moves on and diversifies, instead making antibodies that attach to other parts of the virus. Ideally, this increases the breadth of the immune response—if a virus mutates so that one epitope can no longer be recognized, for example, it might still be vulnerable to antibodies targeting other epitopes.
“Antibody feedback can be a very good thing,” Nussenzweig says. “You end up with a collection of neutralizing antibodies to many different parts of the virus, all of which are helpful.”
But in other cases, antibody feedback can be more harmful than helpful. HIV and influenza both have a limited number of epitopes—and if one epitope doesn’t yield very effective antibodies, a perfect storm may ensue. Upon detecting a surplus of minimally effective antibodies, the body will shut down its production of that line, inadvertently blocking the production of similar antibodies that could potentially have worked better.
Antibody feedback in COVID
To better understand how antibody feedback impacts COVID immunity, Nussenzweig and colleagues followed volunteers who received a single dose of monoclonal antibody treatment and, later, two doses of an mRNA vaccine. They found that these volunteers had markedly different immune responses than individuals who had received the mRNA vaccines alone.
Two doses of an mRNA COVID vaccine usually gives rise to a preponderance of memory B cells, which express antibodies that target one of three key parts of the receptor-binding domain of the spike protein, without which the coronavirus cannot infect a cell. As expected, Nussenzweig and colleagues found that about half of the antibodies obtained from individuals who received only the vaccines targeted so-called Class 1, 2, or 3 epitopes.
But in other cases, antibody feedback can be more harmful than helpful. HIV and influenza both have a limited number of epitopes—and if one epitope doesn’t yield very effective antibodies, a perfect storm may ensue. Upon detecting a surplus of minimally effective antibodies, the body will shut down its production of that line, inadvertently blocking the production of similar antibodies that could potentially have worked better.
“There are only a couple of places on the HIV virus that are worth targeting, and if the initial response blocks those epitopes, we won’t get a broadly neutralizing response,” Nussenzweig says.
The findings suggest that monoclonal antibodies received before vaccination may help diversify the immune response to COVID by increasing the breadth of mRNA vaccines. There may also be important lessons for boosting. “Because there are many targets on the receptor-binding domain that can neutralize the virus, antibody feedback is very helpful,” Nussenzweig says.
And whether the antibody surplus driving that feedback comes from monoclonal antibodies or additional vaccine booster, he says, “antibody feedback is very good for COVID.”
News
Ethics in Nanomedicine: Key Issues and Principles
Nanomedicine, a branch of nanotechnology, is revolutionizing healthcare by enabling the manipulation of materials at the nanoscale to diagnose, treat, and prevent diseases. Unlike traditional treatments, nanoparticles (NPs) are highly precise in targeting diseased [...]
A call for robust H5N1 influenza preparedness and response
As the global threat of H5N1 influenza looms with outbreaks across species and continents including the U.S., three international vaccine and public health experts say it is time to fully resource and support a [...]
Mucosal COVID-19 boosters outperform mRNA shots in preventing upper airway infections
In a recent study published in Nature Immunology, a team of researchers from the United States used non-human primate models to compare the protection conferred by an intramuscular booster dose of the bivalent messenger ribonucleic acid [...]
How Space Travel Really Changes Astronauts – From the Inside Out
International team reveals previously unknown effects on physiology that could shape the future of long-duration space missions. Researchers have discovered significant changes in the gut microbiome due to spaceflight, which affects host physiology and [...]
Breakthrough in blood stem cell development offers hope for leukemia and bone marrow failure
Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalized treatments for children with leukemia [...]
Scientists Develop Game-Changing Needle-Free COVID-19 Intranasal Vaccine
A new mucosal COVID-19 vaccine poised to revolutionize the delivery process is especially beneficial for those with a fear of needles. A next-generation COVID-19 mucosal vaccine is set to be a game-changer not only when delivering [...]
Scientists Develop All-in-One Solution To Catch and Destroy “Forever Chemicals”
A new water treatment system developed by UBC researchers efficiently removes and destroys PFAS pollutants using a dual-action catalyst, offering a sustainable and cost-effective solution for water purification challenges. Chemical engineers at the University of [...]
New method accelerates drug discovery from years to months
Researchers from the University of Cincinnati College of Medicine and Cincinnati Children's Hospital have found a new method to increase both speed and success rates in drug discovery. The study, published Aug. 30 in [...]
A new smart mask analyzes your breath to monitor your health
Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health. [...]
Study reveals the role of blood clotting in COVID-19
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks [...]
A Novel Cancer Vaccine Combining Nano-11 and ADU-S100
In a recent article published in npj Vaccines, researchers detailed the development of a novel cancer vaccine that combines a plant-derived nanoparticle adjuvant, Nano-11, with a clinically tested STING agonist, ADU-S100. The primary objective was [...]
AI spots cancer and viral infections with nanoscale precision
Researchers have developed an artificial intelligence which can differentiate cancer cells from normal cells, as well as detect the very early stages of viral infection inside cells. The findings, published today in a study [...]
Tiny shards of plastic are increasingly infiltrating our brains, study says
Human brain samples collected at autopsy in early 2024 contained more tiny shards of plastic than samples collected eight years prior, according to a preprint posted online in May. A preprint is a study which has not yet [...]
Scientists Have Discovered Strange DNA in Our Brains – and It Could Be Shortening Our Lives
According to the research, these mitochondrial DNA insertions could be linked to early death. Mitochondria in brain cells frequently insert their DNA into the nucleus, potentially impacting lifespan, as those with more insertions were found to [...]
Watch Out After a Hospital Stay: You Could Be Exposing Your Family to Superbugs
Research indicates hospitals contribute to the local spread of antibiotic-resistant infections. A recent study published in the journal Infection Control & Hospital Epidemiology by the Society for Healthcare Epidemiology of America suggests that family members of [...]
Molecular Trickery: How COVID-19 Silently Sabotages the Human Immune System
Researchers have discovered that SARS-CoV-2 manipulates the human immune system by forcing cells to produce non-functional proteins, hindering the body’s antiviral defenses. This groundbreaking study by teams from prestigious Brazilian universities highlights potential targets for new COVID-19 treatments, [...]