Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

For the past few months, there has been a global spread and toll of COVID-19. So far, humanity has been able to eradicate only one other human infectious disease- smallpox. The novel infectious disease- COVID-19 has had its devastating share of lives globally and currently there is no cure or licensed vaccine. 

Many studies lately have been discussing in-depth about neutralizing antibodies. They represent therapeutic and prophylactic options that could help guide potential vaccine designs. Neutralizing antibodies (nAbs) in terms of another respiratory virus- respiratory syncytial virus (RSV) is widely used clinically, usually to protect vulnerable infants prophylactically. Generally, nAbs with good potency also known as super antibodies can supersize antiviral therapeutic efficiency. Along with the help of bioengineering, the nAbs half-life can be prolonged bringing down the cost considerably. 

In this study, the authors try to present potent nAbs to the COVID-19 virus and further demonstrate their efficacy in-vivo using small animal models. The researchers of this paper, isolated and characterized the required monoclonal antibodies from recovering convalescent donors and developed neutralizing assays to investigate the antibody responses. In parallel, the researchers also developed both live attenuated and pseudovirus neutralization assays using HeLa- ACE2 (Angiotensin-converting enzyme) cell line. The collected convalescent plasma was evaluated against COVID-19 by using 8 donors. The antigen-specific B cells were sorted and corresponding genes were identified and cloned to enable antibody expression and characterization. The promising monoclonal antibodies were progressed for further testing in-vivo using a small animal model. 

The study further isolated the potent neutralizing antibodies to two epitopes- the receptor-binding domain (RBD) and the non RBD- Spike (S) protein. The data showed that the passive transfer of neutralizing antibodies provides distinct protection against the novel- COVID-19 virus as seen in Syrian hamsters. The animal model throughout the infection maintained the same weight and showed low lung abnormalities. Nevertheless, as for any animal model, there were a few limitations, including the difference in receptor cells between the hamster and humans.

The results from the study suggest a focus on the RBD and a string neutralizing antibody responses were seen by immunizing mice with a multivalent RBD. The few weak preponderances of neutralizing antibody to S protein may be due to the result of the study using recombinant S protein. In conclusion, the data from the study potentially open up to the idea of the very rapid generation of neutralizing antibodies to a newly emerged novel virus. The antibodies can open up to the possibilities of finding a clinical application and will aid in vaccine manufacturing or design.

Scientists Help Immune System Find Hidden Cancer Cells

Scientists Help Immune System Find Hidden Cancer Cells

Cancer is a widely studied topic in bioscience research but yet remains to be mostly unknown and difficult to treat. However, the recent developments in cancer research over the past decade have helped the scientific community to come up with effective treatment methods. But still, one of the most common problems faced in treating cancer cells is difficulty in locating them for efficient targeting. Recently, scientists from Yale University have developed a new system that can help our immune system find the hidden cancer cells and kill them. The research has been published in Journal Nature Immunology.

Why this study holds importance?

It is a known fact that there exists a number of immunotherapies for treating cancers. But these therapies have certain shortcomings as they either don’t work on all patients or are inefficient in different cancer types. The major reason behind this is the failure of these therapies in identifying the cancer cells which reduces their effectiveness. This highlights an urgent need for a more targeted approach that can help curb the menace of cancer.

The development of a new system by scientists in the present study is considered to overcome the drawbacks of the earlier immune therapies. Researchers report that upon testing the new system in mice it has shown positive response against the melanoma, triple-negative breast, and pancreatic tumors, even for those tumors which are situated at a distant location from the primary tumor.

“This is an entirely new form of immunotherapy,” said Sidi Chen, senior author.

How the new system – MAEGI works?

The researchers developed a new system to target the cancer cells which combines the viral gene therapy and CRISPR based gene-editing technology. Unlike the traditional method of searching and making edits at the DNA level by incorporation of new genes, the present system uses a much more targeted approach.

The new system named as MAEGI stands for Multiplexed Activation of Endogenous Gene as Immunotherapy. This system works by searching numerous cancer-causing genes, marking their location by mimicking GPS and subsequently intensifying the signal of these locations for precise targeting.

For instance, you can consider that the new system dresses up the tumor cells in a unique manner that can be easily identified by the immune system of our body and eventually eliminate them. For this, the cold tumors cells lacking any immune cells are converted into hot tumors cells which are packed with tons of immune cells.

“And once those cells are identified, the immune system immediately recognizes them if they show up in the future,” Chen said. The new system, in theory, should be effective against many cancer types, including those currently resistant to immunotherapy, he said.

The researchers will be further optimizing this system to make the manufacturing process easier. Once optimization is done it will be subjected to clinical trials in potential cancer patients.

No wonder that cancer is a rising menace in the present world. Though many therapies are available we still need highly effective methods to treat cancer. The development of the immunotherapy-based system has given rise to a ray of hope for a more effective and proficient treatment that not only treats primary tumor cells but also the distant ones. Let’s look forward to this new development and hope for the best outcomes in subsequent clinical trials.

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Humans have salamander-like ability to regrow cartilage in joints

Humans have salamander-like ability to regrow cartilage in joints

Recently, scientists at Duke Health have discovered that unlike popular belief, human cartilage have a tendency to repair on its own through a process of limb regeneration similar in salamander and zebrafish. The research has been published in the journal of Science Advances on Oct 9.

Researchers found that the mechanism of the self repair was more robust in ankle joints in comparison to hips. These findings have paved a new path for developing effective treatment methods for osteoarthritis and other associated diseases across the globe.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” said Virginia Byers Kraus, M.D., Ph.D., (Senior author).

Taking a closer look

To understand the entire mechanism of limb regeneration the researchers focused on studying the age of certain proteins. For this, they analyzed the internal molecular clocks integral to amino acids, which convert one form to another. This conversion was quite predictable which helped scientists to establish further details.

They found that newly created protein had very less or no amino acid conversion while the old proteins had many. Using mass spectrometry they analyzed whether these proteins in human cartilage were young, middle-aged or old. Studies showed that the age of cartilage is mainly dependent on its location in the human body. For example, cartilages in the ankle area are found to be young, in kneed its middle age, wherein hips area it was quite old.  This correlation between the location and age of the cartilage indicates how limb regeneration and repair occur in some organisms, wherein the apex parts o the body such as tails or legs showed rapid regeneration. Additionally, it also explains why people with knee or hip injury take more time to recover in comparison to an ankle injury which recovers quicker.

To understand the process in detail, researchers tried to study molecules like microRNA involved in this process. They observed that the microRNA were more active among animal well known for their limb regeneration activity such as lizards, fish, salamanders and more.

These microRNA are also known to be present in humans, offering natural competence of tissue repairs. It is higher in the top layers of cartilage in comparison to the deeper layers.

“We were excited to learn that the regulators of regeneration in the salamander limb appear to also be the controllers of joint tissue repair in the human limb,” Hsueh said. “We call it our ‘inner salamander’ capacity.”

The researchers said microRNAs could be developed as medicines that might prevent, slow or reverse arthritis.

“We believe we could boost these regulators to fully regenerate degenerated cartilage of an arthritic joint. If we can figure out what regulators we are missing compared with salamanders, we might even be able to add the missing components back and develop a way someday to regenerate part or all of an injured human limb,” Kraus said. “We believe this is a fundamental mechanism of repair that could be applied to many tissues, not just cartilage.”

Scientists Help Immune System Find Hidden Cancer Cells

Scientists Help Immune System Find Hidden Cancer Cells

Cancer is a widely studied topic in bioscience research but yet remains to be mostly unknown and difficult to treat. However, the recent developments in cancer research over the past decade have helped the scientific community to come up with effective treatment methods. But still, one of the most common problems faced in treating cancer cells is difficulty in locating them for efficient targeting. Recently, scientists from Yale University have developed a new system that can help our immune system find the hidden cancer cells and kill them. The research has been published in Journal Nature Immunology.

Why this study holds importance?

It is a known fact that there exists a number of immunotherapies for treating cancers. But these therapies have certain shortcomings as they either don’t work on all patients or are inefficient in different cancer types. The major reason behind this is the failure of these therapies in identifying the cancer cells which reduces their effectiveness. This highlights an urgent need for a more targeted approach that can help curb the menace of cancer.

The development of a new system by scientists in the present study is considered to overcome the drawbacks of the earlier immune therapies. Researchers report that upon testing the new system in mice it has shown positive response against the melanoma, triple-negative breast, and pancreatic tumors, even for those tumors which are situated at a distant location from the primary tumor.

“This is an entirely new form of immunotherapy,” said Sidi Chen, senior author.

How the new system – MAEGI works?

The researchers developed a new system to target the cancer cells which combines the viral gene therapy and CRISPR based gene-editing technology. Unlike the traditional method of searching and making edits at the DNA level by incorporation of new genes, the present system uses a much more targeted approach.

The new system named as MAEGI stands for Multiplexed Activation of Endogenous Gene as Immunotherapy. This system works by searching numerous cancer-causing genes, marking their location by mimicking GPS and subsequently intensifying the signal of these locations for precise targeting.

For instance, you can consider that the new system dresses up the tumor cells in a unique manner that can be easily identified by the immune system of our body and eventually eliminate them. For this, the cold tumors cells lacking any immune cells are converted into hot tumors cells which are packed with tons of immune cells.

“And once those cells are identified, the immune system immediately recognizes them if they show up in the future,” Chen said. The new system, in theory, should be effective against many cancer types, including those currently resistant to immunotherapy, he said.

The researchers will be further optimizing this system to make the manufacturing process easier. Once optimization is done it will be subjected to clinical trials in potential cancer patients.

No wonder that cancer is a rising menace in the present world. Though many therapies are available we still need highly effective methods to treat cancer. The development of the immunotherapy-based system has given rise to a ray of hope for a more effective and proficient treatment that not only treats primary tumor cells but also the distant ones. Let’s look forward to this new development and hope for the best outcomes in subsequent clinical trials.

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Mucus is more just than a physical barrier for microbes

Mucus is more just than a physical barrier for microbes

Do you know that the mucus in our body has a much greater role to play than just forming a physical barrier for microbes? Recent research by scientists at MIT reveals that the glycans in mucus can hinder communication between microbes rendering them harmless by forming an infectious biofilm.

The researcher Katharine Ribbeck has been studying the underlying biochemistry of mucus for over a decade. “Mucus piqued my interest because it is just this vastly understudied material that occupies a large surface area in our body,” – Ribbeck.

On average, a person produces a liter of mucus every day, which is used by our body to protect against harmful microbes. Mucus lines numerous organs in our body such as digestive tracts, urinary tracts, and lungs. It acts as a lubricant and physical barrier blocking the microbial invasion.

The study focuses on unwinding the role of mucins in mucus. Mucins are proteins densely packed with chains of sugar. Till date, very little research has been done in this area. This highlights the importance of the present study as it lays the foundation for further studies to understand the role of mucus in our body.

Unwinding the role of glycans

The scientists were very much interested in understanding the role of glycans in regulating microbial behavior. These glycans are known for attaching to proteins known as mucins, responsible for the characteristic gel-like nature of the mucus. To gain deeper insights scientists subjected the isolated glycans against Pseudomonas aeruginosa, which is a pathogen causing infection among people with compromised immune system. The findings showed that the mucin glycans rendered the microbes to become less harmful by altering their behavior. For example, the microbial cells didn’t show any toxin production, killing of host cells or attaching to the surface of host cells, and expression of genes playing a role in bacterial communication. Researchers further supported their finding by showing the role of mucin glycans in reducing the bacterial proliferation in Pseudomonas infected wounds.

Future prospects of the discovery

The present study has unraveled the important role of mucus in overcoming the bacterial infection. To take this ahead, researchers are now looking forward to developing artificial mucus which can provide new insights to treat diseases and infections stemming from mucus. The researcher (Ribbeck) said, “Harnessing the powers of mucus could also lead to new ways to treat antibiotic-resistant infections because it offers a complementary strategy to traditional antibiotics”.

“What we find here is that nature has evolved the ability to disarm difficult microbes, instead of killing them. This would not only help limit selective pressure for developing resistance because they are not under pressure to find ways to survive, but it should also help create and maintain a diverse microbiome,” – Ribbeck

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Aspirin can reduce air pollution effect on lungs

Aspirin can reduce air pollution effect on lungs

Aspirin is widely used for treating headaches but do you know it can also have functional value in relieving your lungs from pollution damage? Recent research by scientists from Columbia Mailman School of Public Health, Boston University School of Medicine and Harvard Chan School of Public Health has revealed the potential aspects of aspirin in reducing the impact of pollution on lungs. The research has been published in the American Journal of Respiratory and Critical Care Medicine.

Pollutants in the air can harm your body by causing severe damage to the lung cells. This mainly includes inflammation and irritation in the cells which can become more serious if not taken care of. It does make sense now why researchers choose aspirin as an agent to curb the menace of pollution. Aspirin is a non-steroidal anti-inflammatory drug (NSAIDs) which has a defensive effect in response to inflammatory reactions in the body.

In the present research, scientists collected the data of more than 2000 male veterans belonging to the Boston area with an average age of 73 years. The functionality of the lungs of this cohort was evaluated to gain better insights for further comparative analysis (since 1960). Moreover, the data for air pollution was also analyzed (since 1955) regularly.

Researchers compared the functionality of the lungs of volunteers under the influence of NSAIDs and those who are not. They observed that the group with exposure to NSAID showed the reduced impact of particulate matter and black carbon on the lungs in comparison to those without NSAID administration. The study also considered other factors such as the health of the volunteers and smoking habits to come up with precise result analysis. The results were found to be consistent throughout the study sessions for all weekly air pollution measurements from the initial day of inspection until the day of the lung function test.

Researchers found that most of the volunteers consuming NSAID mainly used aspirin. This highlights the improved response observed among volunteers can be contributed by aspirin. However, other non-aspirin NSAIDs can also be explored to understand the overall effectiveness and association with a lung condition.

“Our findings suggest that aspirin and other NSAIDs may protect the lungs from short-term spikes in air pollution,” says corresponding author Xu Gao, a scientist in the Department of Environmental Health Sciences at the Columbia Mailman School. He added, “Of course, it is still important to minimize our exposure to air pollution, which is linked to a host of adverse health effects, from cancer to cardiovascular disease.”

The findings support the use of aspirin in overcoming the harm caused by pollution to the human lungs. Though the exact mechanism of working is not yet known, the study paves the path for the researcher to speculate and evaluate the role of NSAIDs in overcoming the inflammatory responses due to severe pollution exposure. Further detailed studies are needed to evaluate the impact and understand the mechanism at a molecular level.

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