Tag: antibodies

Categories : COVIDTags :

Scientists Pry Open Secrets of a Potent Antibody against COVID

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Even as the structure of SARS-CoV-2 changes with different variants of the virus (grey), the J08 antibody (blue) can still bind it, Scripps researchers showed. Credit: Scripps Research

Scientists have revealed the secrets of a potent antibody against SARS-CoV-2 that was discovered in COVID survivors. The antibody has a broadly neutralising effect, and is able to retain its efficacy against a wide range of variants – though not Omicron.

In 2021, Scripps Research and Toscana Life Sciences scientists screened the blood of 14 COVID-19 survivors to find the most potent antibodies against the SARS-CoV-2 virus. One of the most promising finds, now in stage II/III trials, was an antibody dubbed J08, which seemed to be capable of both preventing and treating COVID. 

Now, the same group has visualised exactly how J08 binds to different SARS-CoV-2 variants in different conformations, explaining what makes the monoclonal antibody so potent. The research, published in Proceedings of the National Academy of Sciences, suggests that the J08 antibody’s flexibility will likely keep it effective against future COVID variants.

“Even though we can’t predict what variants of COVID will emerge next, understanding the details of J08 reveals what works against the virus, and perhaps how we can engineer antibodies to be even more potent,” explained senior author Andrew Ward, PhD at Scripps Research.

On exposure to a virus like SARS-CoV-2, the body creates a variety of antibodies that bind to different sections of the virus to clear it from the body. There is considerable interest in why certain naturally produced antibodies such as J08 more effective than others. In the months after Ward and his collaborators first identified J08, it became clear that the antibody, unlike many others, was potent against a variety of COVID variants.

The researcher mapped the three-dimensional structure of J08 as it bound to the spike protein of SARS-CoV-2. J08 was confirmed to successfully attach to the Alpha, Beta, Gamma and Delta variants, preventing replication. However, J08 attached to the Omicron variant about 7 times more slowly, and then quickly detached. About 4000 times more J08 was needed to fully neutralise Omicron SARS-CoV-2 compared to the other variants.

“With variants other than Omicron, this antibody binds quickly and doesn’t come off for hours and hours,” says co-first author Gabriel Ozorowski, a senior staff scientist in the Ward lab at Scripps Research. “With Omicron, we were initially happy to find that it still binds, but it falls off very quickly. We identified the two structural changes that cause this.”

The team showed that, for all the variants, J08 binds to a very small section of the virus – a section that generally stays the same even as the virus mutates. Moreover, J08 could attach in two completely different orientations, like a key that manages to unlock a door whether it is right side up or upside down. 

“This small, flexible footprint is part of why J08 is able to withstand so many mutations – they don’t impact the antibody binding unless they happen to be in this one very small part of the virus,” said co-first author Jonathan Torres, lab manager of the Ward lab at Scripps Research.

The Omicron variant of SARS-CoV-2, however, had two mutations (known as E484A and Q493H) that changed the small area of the virus that directly interfaces with J08, anchoring it in place. Ward and his collaborators found that if just one of these mutations is present, J08 can still bind and neutralise the virus strongly, but mutations in both are what make it less effective against the Omicron variant.

The researchers said the new results support the continued clinical trials of the monoclonal antibody based on J08.

“I think we’re pretty confident that future variants won’t necessarily have both of these two critical mutations at the same time like Omicron,” remarked Ozorowski, “so that makes us hopeful that J08 will continue being very effective.”

Source: Scripps Research

Categories : HIVTags :

Anti-HIV Antibodies Achieve Viral Suppression

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HIV Infecting a T9 Cell. Credit: NIH

A trial has successfully used a novel treatment of anti-HIV antibodies to achieve viral suppression in several HIV patients. The results published in Nature, would enable a treatment not reliant on vigilant daily dosing and which could potentially reduce the body’s reservoir of HIV, something antiretroviral drugs cannot do. The antibody treatment could be used in combination with long-acting antiretrovirals, or alone after such medications have sufficiently brought down viral levels.

“The idea is that you would still be on HIV treatment, but instead of having to take a pill every day, with the long-acting versions of the antibodies, patients would be able to take infusions every six months,” said Professor Marina Caskey, who co-led the study.

In this trial, 18 participants received seven infusions of a pair of broadly neutralising antibodies over five months, while discontinuing their antiretroviral medications. Thirteen of these participants maintained viral suppression for at least five months, and in a few cases over a year, suggesting the antibodies are able to control viruses that are sensitive to the antibodies and prevent viral levels from rising to dangerous levels.

Besides suppressing the virus, antibody therapy may also have an effect on cells infected with HIV that cannot be eliminated by antiretroviral drugs. “Ultimately, with any treatment, we’d like to see a decline in the reservoir of infected T-cells, which fuel rebound when therapy is discontinued,” says Christian Gaebler, an assistant professor of clinical investigation in Nussenzweig’s lab and the study’s first author. After therapy, the team detected a decrease in the infected T-cells, specifically those that harbor intact viruses capable of replication. “It’s a promising finding that we hope to follow up on in future, larger studies,” Gaebler says.

The new study built on a previous, shorter trial in which participants had received three antibody infusions over six weeks. The researchers found that administering additional infusions was generally safe and well-tolerated, and the longer treatment period did not result in the emergence of new resistant variants.

Source: Rockefeller University

Categories : COVIDTags :

Prior COVID Infection Results in Robust Immunity after Vaccination

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Vaccine injection
Image source: NCI on Unsplash

New research published in the journal JCI Insight shows that immune responses to the Pfizer-BioNTech mRNA vaccine differ significantly in individuals depending on whether or not they had a prior COVID infection. Notably, those who had COVID before vaccination produced a surge of antibodies after the first dose, with little or no increase seen after the second dose. The opposite pattern was observed in infection-naïve individuals.

“Our study shows that the presence of immune memory induced by prior infection alters the way in which individuals respond to SARS-CoV-2 mRNA vaccination,” explained first author Professor Steven G. Kelsen. “The lack of response after the second vaccine dose in previously infected individuals is especially relevant, because it could mean that some people may require only one dose or could potentially skip the booster shot.”

Prof Kelsen and colleagues carried out the study in health care workers, some having previously tested positive for SARS-CoV-2 infection and others never having been infected. The researchers measured levels of neutralising antibodies in blood samples taken at three different time points, including before vaccination and after each vaccine dose. They also performed qualitative assessment for local reactions and systemic symptoms, such as fever, headache, and fatigue, associated with vaccination.

While levels of neutralising antibodies hit their maximum in some people with prior COVID after the first vaccine dose, individuals with no history of infection showed massive responses after the second dose. Those high levels also plummeted quickly, while the COVID group retained longer lasting immunity, despite the lack of response to a second dose. However, prior infection was also linked to more frequent and longer-lasting adverse reactions to the vaccine.

“Previous studies had similarly reported long-lasting immunity and strong immune reactions in COVID patients,” Prof Kelsen said. “We now provide new information on how prior infection interacts with vaccination in terms of measurable immune response and how individuals react to mRNA vaccines based on infection history.”

The next steps for Prof Kelsen and collaborators are to modify their neutralising antibody assay to detect Omicron and other SARS-CoV-2 variants. “We also are interested in understanding how long protection from a booster dose of the vaccine lasts,” he said.

Source: EurekAlert!

Categories : AgeingTags :

Fewer Types of Antibodies Produced with Age

On By ModernMedia
old man walking with canes
Source: Miika Luotio on Unsplash

Using short-lived killifish to study how the immune system weakens with ageing, scientists have found that fewer types of antibodies are produced as organisms age. Published in eLife, the findings could lead to ways to rejuvenate the immune systems of older people.

The immune system has to constantly respond to new attacks from pathogens and remember them in order to be protected during the next infection. For this purpose, B cells build a library of information that can produce a variety of antibodies to recognise the pathogens.

“We wanted to know about the antibody repertoire in old age,” explained lead researcher Dario Riccardo Valenzano. “It is difficult to study a human being’s immune system over his or her entire life, because humans live a very long time. Moreover, in humans you can only study the antibodies in peripheral blood, as it is problematic to get samples from other tissues. For this reason, we used the killifish. It is very short-lived and we can get probes from different tissues.”

The shortest-lived vertebrates that can be kept in the laboratory, killifishes quickly age over their three to four month lifespan and have become the focus of ageing research in recent years due to these characteristics.

The researchers were able to accurately characterise all the antibodies that killifish produce. They found that older killifish have different types of antibodies in their blood than younger fish. They also had a lower diversity of antibodies throughout their bodies.

The discovery could lead to ways to rejuvenate the immune system. “If we have fewer different antibodies as we age, this could lead to a reduced ability to respond to infections. We now want to further investigate why the B cells lose their ability to produce diverse antibodies and whether they can possibly be rejuvenated in the killifish and thus regain this ability,” Valenzano said.

Source: Max Planck Institute for Biology of Ageing

Categories : VaccinesTags :

Exercise After Vaccination Boosts Antibodies

On By ModernMedia
Photo by Barbra Olsen on Pexels

Researchers have found that a 90 minute bout of mild- to moderate-intensity exercise directly after a receiving a flu or COVID vaccine may provide an extra immune boost.

In the paper, published in Brain, Behavior, and Immunity, participants who cycled on a stationary bike or took a brisk walk for an hour-and-a-half after receiving a vaccine injection produced more antibodies in the following four weeks compared to participants who sat or continued with their daily routine post-immunisation. When the researchers ran the experiment with mice and treadmills, similar results were observed.

“Our preliminary results are the first to demonstrate a specific amount of time can enhance the body’s antibody response to the Pfizer-BioNtech COVID vaccine and two vaccines for influenza,” said Kinesiology Professor Marian Kohut, lead author of the study.

The vaccine recipients would be able to benefit people who could not cope with such exercise. Nearly half of the participants in the experiment had a BMI in the overweight or obese category. During 90 minutes of exercise, they focused on maintaining a pace that kept their heart rate around 120–140 beats per minute rather than distance.

However, the exercise duration appeared to be important: the researchers also ran the experiment with just 45-minutes of exercising. The shorter workout did not increase the participants’ antibody levels. Prof Kohut said a follow-up study might test whether 60 minutes is sufficient.

As to why prolonged, mild- to moderate-intensity exercise could improve the body’s immune response, Prof Kohut said there may be multiple reasons. Exercise increases blood and lymph flow, which helps circulate immune cells. As these cells move around the body, they’re more likely to detect antigens. The mouse experiment data also suggested that interferon alpha produced during exercise helps generate virus-specific antibodies and T- cells.

“A lot more research is needed to answer the why and how,” said Prof Kohut. “There are so many changes that take place when we exercise – metabolic, biochemical, neuroendocrine, circulatory. So, there’s probably a combination of factors that contribute to the antibody response we found in our study.”

The researchers are continuing to track the antibody response in the participants six months post-immunisation and have launched another study that focuses on exercise’s effects on people who receive booster shots.

Source: Iowa State University

Categories : Ageing COVIDTags :

Previously Infected Older People Have More COVID Antibodies

On By ModernMedia
Photo by Adam Birkett on Unsplash

In a recent study published in Scientific Reports, researchers found that older people previously infected with COVID, when vaccinated, had higher antibody levels than previously infected individuals. These antibodies were also effective against the Delta variant, which wasn’t present in Canada when the samples were taken  in 2020.

Joelle Pelletier and Jean-François Masson, both professors in Université de Montréal’s Department of Chemistry, wanted to find out whether natural infection or vaccination led to more protective antibodies being generated. The focussed on an understudied group: people who have been infected but not hospitalised by SARS-CoV-2.

Consequently, 32 non-hospitalised COVID positive adults were recruited 14 to 21 days after being diagnosed through PCR testing. This was in 2020, before the Beta, Delta and Gamma variants emerged.

“Everyone who had been infected produced antibodies, but older people produced more than adults under 50 years of age,” said Prof Masson. “In addition, antibodies were still present in their bloodstream 16 weeks after their diagnosis.”

Antibodies produced after an infection by the original, “native” strain of the virus also reacted to SARS-CoV-2 variants that emerged in subsequent waves, namely Beta (South Africa), Delta (India) and Gamma (Brazil), but to a lesser extent: a reduction of 30 to 50%.

“But the result that surprised us the most was that antibodies produced by naturally infected individuals 50 and older provided a greater degree of protection than adults below 50, ” said Prof Pelletier.

“This was determined by measuring the antibodies’ capacity to inhibit the interaction of the Delta variant’s spike protein with the ACE-2 receptor in human cells, which is how we become infected,” he added. “We didn’t observe the same phenomenon with the other variants.”

When someone who has had a mild case of COVID is vaccinated, the antibody level in their blood doubles compared to an unvaccinated person who has been infected by the virus. Their antibodies are also better able to prevent spike-ACE-2 interaction.

“But what’s even more interesting,” said Prof Masson, “is that we have samples from an individual younger than 49 whose infection didn’t produce antibodies inhibiting spike-ACE-2 interaction, unlike vaccination. This suggests that vaccination increases protection against the Delta variant among people previously infected by the native strain.”

Both scientists believe more research should be conducted to determine the best combination for maintaining the most effective level of antibodies reactive to all variants of the virus.

Source: University of Montreal

Categories : Diseases, Syndromes and ConditionsTags :

How Antibody Treatment for MIS-C Works

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Source: NCI on Unsplash

The depletion of neutrophils could be how intravenous immune globulin (IVIG) is able to treat multisystem inflammatory syndrome in children (MIS-C).

MIS-C is a rare condition that usually affects school-age children who initially had only mild COVID symptoms or no symptoms at all. The researchers also found that IVIG works in a similar manner for treating Kawasaki disease, another rare inflammatory condition that affects children and shares symptoms with MIS-C. 

MIS-C is marked by severe inflammation of two or more parts of the body, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal organs. Its symptoms overlap with Kawasaki disease, and treatments for MIS-C are partly guided by what is known about the treatment of Kawasaki disease. IVIG, which is made up of antibodies purified from blood products, is a common and effective treatment for heart complications caused by Kawasaki disease. For MIS-C patients, however, IVIG alone does not always resolve symptoms, and healthcare providers may need to prescribe additional anti-inflammatory drugs.

In order to better understand how IVIG works and to improve treatments for children with MIS-C, researchers profiled immune cells from patients with MIS-C or Kawasaki disease. The team sampled cells before treatment began as well as 2 to 6 weeks after patients received IVIG, and found that neutrophils from these patients were highly activated and a major source of interleukin 1 beta (IL-1β), a driver of inflammation. After IVIG treatment, these activated neutrophils were significantly depleted in patients with MIS-C or Kawasaki disease.

The study authors believe their findings are the first to explain why IVIG is effective for both conditions. More work is needed however to understand how IVIG causes cell death in these activated neutrophils and why certain patients with MIS-C require additional anti-inflammatory treatments.

The findings appear in the Journal of Clinical Investigation.

Source: National Institutes of Health

Categories : COVIDTags :

Anti-Spike Antibodies Key for Surviving Severe COVID

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SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

In a study of patients with COVID being treated in intensive care units, people mounting only a low antibody response against the SARS-CoV-2 virus had a greater risk of dying. 

Previous studies by the researchers had indicated that levels of SARS-CoV2 viral RNA and antigens in the blood was related to COVID severity.

The study, which is published in the Journal of Internal Medicine, recruited 92 patients severely ill with COVID who were admitted to the ICU. The researchers found that patients with strong antibody responses against the virus had low levels of viral RNA in their blood, especially anti-S (Spike protein) antibodies. Those with poor antibody responses had high viral RNA levels and disseminated viral proteins in the blood, 2.5 times higher than those with strong antibody responses. 

Previous studies have shown that critical COVID patients develop higher titers of SARS-CoV-2 antibodies than those with milder disease, suggesting that antibody response alone is insufficient to avoid severe disease. The findings nonetheless support that critical COVID patients would need to mount a robust anti-S antibody response to survive.

The results could help establish the optimal antibody levels needed for an individual to overcome COVID when critically ill. The study also provided evidence of the importance of antibodies against the Spike protein of SARS-CoV-2 to block the virus’ replication, which are the antibodies induced by vaccination.  

“Our findings support that treatment with exogenous antibodies in COVID should be personalised, reserving this therapy for those patients with absent or low endogenous antibodies levels,” said co–senior author Jesús F. Bermejo-Martin, MD, PhD, of the Instituto de Investigación Biomédica de Salamanca (IBSAL) & CIBERES, in Spain.

Source: Wiley

Categories : COVIDTags :

Antibody COVID Prophylactic Cocktail Performs Well in Trials

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Source: NCI on Unsplash

A COVID prophylactic cocktail of long-acting antibodies cut the risk of developing symptomatic disease in a high-risk unvaccinated patient population, AstraZeneca announced on Friday.

Initial phase III trial data showed that AZD7442 (tixagevimab and cilgavimab) as pre-exposure prophylaxis significantly reduced the risk of developing COVID symptoms by 77% versus placebo, meeting the trial’s primary endpoint.
AstraZeneca further noted there were no cases of severe COVID or COVID-related deaths in the intervention group, while there were three cases of severe COVID and two deaths in the placebo group.

No safety concerns were noted by the manufacturer, as the treatment was well-tolerated and adverse events were balanced between groups.

A key feature of the trial was that 75% of participants had comorbidities, including being “at risk of an inadequate response to active [immunisation],” such as older adults and those with immunosuppressive disease or on immunosuppressive medication.

“With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives,” the trial’s principal investigator, Myron Levin, MD, of the University of Colorado School of Medicine, said in a statement.

AZD7442 was derived from the B cells of convalescent patients. PROVENT was a phase III randomised trial conducted in the US and Europe. Participants were 5197 adults “who would benefit from prevention” with the long-acting antibody, were unvaccinated at the time of enrollment, and tested negative for SARS-CoV-2.
Participants were randomised 2:1 to receive a single 300 mg dose of AZD7442 or placebo. AstraZeneca noted that 43% of participants were ages 60 and older. The company noted that the drug is active in lab studies against emerging strains, including the Delta variant.

Patients were followed for 183 days, though subjects are slated to be followed for 15 months, AstraZeneca said. Data will be submitted for peer-reviewed publication while the company seeks approval for AZD7442.

Source: MedPage Today

Categories : Gender Obstetrics & GynaecologyTags :

A New Antibody-based Contraceptive for Women

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Photo by nine koepfer on Unsplash
Photo by nine koepfer on Unsplash

Researchers have developed a topical antibody-based contraceptive for use by women, which works like a glue, clumping and trapping sperm. 

Over 40 percent of pregnancies worldwide are unintended, even though multiple forms of contraception are available. As well as fuelling population growth, unintended pregnancies can negatively impact the physical, mental and economic wellbeing of mothers.

To address these problems, researchers from Boston University School of Medicine and ZabBio have developed an anti-sperm monoclonal antibody, the Human Contraception Antibody (HCA), which laboratory tests showed was safe and had potent sperm agglutination (clumping) and immobilisation activity.

“HCA appears to be suitable for contraceptive use and could be administered vaginally in a dissolvable film for a woman-controlled, on-demand birth control method,” explained senior author Deborah Anderson, PhD, professor of Medicine.

In order to assess its applicability as a topical contraceptive, the team tested HCA over a wide range of concentrations and under different physiologically relevant conditions in vitro. HCA was mixed with sperm from normal, healthy volunteers and then tested. Sperm became immobilised within 15 seconds, becoming stuck together. The researchers also found that HCA did not seem to cause vaginal inflammation in lab tissue culture tests.

Thanks to its safety and efficacy, HCA could fill current gaps in the contraception field. “HCA could be used by women who do not use currently available contraception methods and may have a significant impact on global health,” said Prof Anderson.  HCA is currently being tested in a Phase I Clinical Trial.

The researchers also believe that a combination of HCA with other antibodies such as anti-HIV and anti-HSV antibodies could make a multipurpose prevention technology, a product that would both serve as a contraceptive and prevent sexually transmitted infections.

These findings appear online in the journal EBioMedicine.

Source: Boston University School of Medicine

Journal information: Gabriela Baldeon-Vaca et al, Production and characterization of a human antisperm monoclonal antibody against CD52g for topical contraception in women, EBioMedicine (2021). DOI: 10.1016/j.ebiom.2021.103478