Holistic Immune Response Against Covid-19

Researchers say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers the immune system sends out to destroy infected cells. Until now, COVID vaccines have focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

As reported in the journal Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body.

Companies should reevaluate their vaccine designs,” says Mohsan Saeed, a virologist at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and co-corresponding author of the paper.

Saeed, an assistant professor of biochemistry at the School of Medicine, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs.

This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved when computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay contacted him. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.

The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology.

We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

Source:  https://www.futurity.org/

Hunting for the Coronavirus’s Origin

More than a year after Covid-19 touched off the worst pandemic in more than a century, scientists have yet to determine its origins. The closest related viruses to SARS-CoV-2 were found in bats over 1,000 miles from the central Chinese city of Wuhan, where the disease erupted in late 2019. Initially, cases were tied to a fresh food market and possibly the wildlife sold there. An investigation in early 2021 has highlighted the possibility that they acted as a vector, transferring the virus from bats to humans. More politically charged theories allege the virus accidentally escaped from a nearby research laboratory, or entered China from another country via imported frozen food. Amid all the posturing, governments and scientists agree that deciphering the creation story.

Three closely related viruses to SARS-CoV-2 that had been collected during the previous 15 years. The closest, about 96% identical, was isolated from a species of horseshoe bat, Rhinolophus affinis, in the southern Chinese province of Yunnan in 2013. Some researchers have linked that particular virus to a mineshaft in Mojiang county there, where six men contracted a pneumonia-like disease in 2012 that killed three of them. Although they may share a common ancestor, the two are not similar enough to indicate SARS-CoV-2 was derived from the Yunnan virus. Sampling of bats in Hubei province, which includes Wuhan, haven’t found any positive for the pandemic strain. Coronaviruses sharing genetic features with SARS-CoV-2 have been found in other bat species and pangolins, a scaly, ant-eating mammal, elsewhere in Asia, highlighting the broad distribution that may have contributed to its evolution.

https://www.bloomberg.com/

COVID-19 Can Cause Antibodies that Mistakenly Target your Own Tissues

An increasing body of research is pointing toward the possibility that COVID-19 causes the development of autoantibodies linked to other autoimmune diseases — and may be tied to the long-hauler symptoms associated with coronavirus.

In the latest preprint study (which means it has not yet undergone peer review) researchers analyzed the levels of 18 different autoantibodies between four groups:

  • 29 unexposed pre-pandemic individuals from the general population
  • 20 individuals hospitalized with moderate-to-severe COVID-19
  • 9 recovering COVID-19-infected individuals with asymptomatic to mild viral symptoms during the acute phase, with samples collected between 1.8 and 7.3 months after infection
  • 6 unexposed pre-pandemic subjects with lupus (an autoimmune disease that involves different kinds of autoantibodies)
  • Autoantibodies are antibodies that mistakenly target your own tissues or organs and are associated with diseases such as rheumatoid arthritis and lupus. Unsurprisingly, the researchers found that autoantibodies were detected in five out of the six lupus subjects, compared to just 11 of 29 non-lupus, pre-pandemic controls.

However, the researchers also found that autoantibodies were detected in seven out of nine patients recovering from SARS-CoV-2 and in 12 out of the 20 hospitalized individuals with moderate to severe COVID-19. In the first group, autoantibodies were detected in all patients with reported persistent symptoms and two of the four without any long-term symptoms.

The autoantibodies that set SARS-CoV-2  infected patients apart from the pre-pandemic subjects are widely associated with myopathies (neuromuscular disorders), vasculitis (inflammation of the blood vessels), and antiphospholipid syndromes (when your body creates antibodies that make your blood much more likely to clot), all of which are conditions that share some similarities with COVID-19. The researchers note that these results underscore the importance of further investigating autoimmunity during a COVID-19 infection, and the role of autoimmunity in lingering symptoms. That said, they do urge caution in interpreting the results, which still need to undergo peer review.

It’s a signal; it is not definitive,” lead researcher Nahid Bhadelia, MD, told the New York Times. We don’t know how prevalent it is, and whether or not it can be linked to long COVID.” (Long COVID is sometimes used to describe the syndrome that causes long-hauler symptoms in those who have recovered from COVID-19.)

Still, as many as one-third of COVID-19 survivors say they still experience symptoms — and determining the role autoimmunity may play after coronavirus infection is critical.

This is a real phenomenon,” Dr. Bhadelia said. “We’re looking at a second pandemic of people with ongoing potential disability who may not be able to return to work, and that’s a huge impact on the health symptoms.”

Source: https://creakyjoints.org/
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https://www.medrxiv.org/

Summer Sunlight Could Inactivate 90% of Coronavirus Particles in 30 minutes

A team of scientists is calling for greater research into how sunlight inactivates SARS-CoV-2 after realizing there’s a glaring discrepancy between the most recent theory and experimental results. UC Santa Barbara mechanical engineer Paolo Luzzatto-Fegiz and colleagues noticed the virus was inactivated as much as eight times faster in experiments than the most recent theoretical model predicted.

The theory assumes that inactivation works by having UVB hit the RNA of the virus, damaging it,” explained Luzzatto-Fegiz.

But the discrepancy suggests there’s something more going on than that, and figuring out what this is may be helpful for managing the virus.

UV light, or the ultraviolet part of the spectrum, is easily absorbed by certain nucleic acid bases in DNA and RNA, which can cause them to bond in ways that are hard to fix.

But not all UV light is the sameLonger UV waves, called UVA, don’t have quite enough energy to cause problems. It’s the mid-range UVB waves in sunlight that are primarily responsible for killing microbes and putting our own cells at risk of Sun damage.

Short-wave UVC radiation has been shown to be effective against viruses such as SARS-CoV-2, even while it’s still safely enveloped in human fluids.

But this type of UV doesn’t usually come into contact with Earth’s surface, thanks to the ozone layer.

UVC is great for hospitals,” said co-author and Oregon State University toxicologist Julie McMurry. “But in other environments – for instance, kitchens or subways – UVC would interact with the particulates to produce harmful ozone.”

In July 2020, an experimental study tested the effects of UV light on SARS-CoV-2 in simulated saliva. They recorded the virus was inactivated when exposed to simulated sunlight for between 10-20 minutes.

Natural sunlight may be effective as a disinfectant for contaminated nonporous materials,” Wood and colleagues concluded in the paper.

Luzzatto-Feigiz and team compared those results with a theory about how sunlight achieved this, which was published just a month later, and saw the math didn’t add up. his study found the SARS-CoV-2 virus was three times more sensitive to the UV in sunlight than influenza A, with 90 percent of the coronavirus‘s particles being inactivated after just half an hour of exposure to midday sunlight in summer.

By comparison, in winter light infectious particles could remain intact for days.

Source: https://www.news.ucsb.edu/
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https://www.sciencealert.com/

New Nanoparticle-delivered COVID-19 Vaccine

Researchers from Cleveland Clinic’s Global Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that utilizes nanotechnology and has shown strong efficacy in preclinical disease models.

According to new findings published in mBio, the vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the vaccine candidate’s early appeal is that it may be thermostable, which would make it easier to transport and store than currently authorized COVID-19 vaccines.

Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin–a protein found in almost all living organisms,” said Jae Jung, PhD, director of the Global Center for Human Health & Pathogen Research and co-senior author on the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”

Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and co-first author on the study, “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”

Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza.

The team’s vaccine uses the ferritin nanoparticles to deliver tiny, weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human entry point for the virus (this fragment is called the receptor-binding domain, or RBD). When the SARS-CoV-2 RBD binds with the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.

The researchers tested their vaccine candidate on a ferret model of COVID-19, which reflects the human immune response and disease development better than other preclinical models. Dr. Jung, a foremost authority in virology and virus-induced cancers, previously developed the world’s first COVID-19 ferret model–a discovery that has significantly advanced research into SARS-CoV-2 infection and transmission.

Source: https://www.lerner.ccf.org/
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https://www.eurekalert.org/

Janssen Vaccine could be Rolled Out in Europe by March 15

The European Medicines Agency (EMA) has received an application for conditional marketing authorisation (CMA) for a COVID-19 vaccine developed by Janssen-Cilag International N.V. Janssen is a subsidiary of the giant pharma-company Johnson & Johnson.

EMA’s human medicines committee (CHMP) will assess the vaccine, known as COVID-19 Vaccine Janssen, under an accelerated timetable. The Committee could issue an opinion by the middle of March 2021, provided the company’s data on the vaccine’s efficacy, safety and quality are sufficiently comprehensive and robust.

Such a short time for evaluation is only possible because EMA has already reviewed some data during a rolling review. During this phase, EMA assessed quality data and data from laboratory studies which looked at how well the vaccine triggers the production of antibodies and immune cells that target SARS-CoV-2 (the virus that causes COVID-19). The Agency also looked at clinical safety data on the viral vector used in the vaccine.

EMA is now assessing additional data on the efficacy and safety of the vaccine as well as its quality. If EMA concludes that the benefits of the vaccine outweigh its risks, it will recommend granting a CMA. The European Commission will then issue a decision on whether to grant a CMA valid in all EU and EEA Member States within days.

This is the fourth CMA application for a COVID-19 vaccine since the start of the current pandemic. It comes after EMA’s evaluation of vaccines from BioNTech/Pfizer, Moderna and AstraZeneca. These vaccines are now authorised in the EU and are among the tools Member States are using to combat COVID-19.

Source: https://www.ema.europa.eu/

The Vaccination against Covid-19 Prevents the Transmission of the Virus

A growing body of evidence suggests that the Covid-19 vaccine can slow the spread of the coronavirus, Dr. Anthony Fauci said Wednesday. Whether vaccination can prevent transmission of the virus is “the looming question,” Fauci, director of the National Institute of Allergy and Infectious Diseases, said during a White House coronavirus response team briefing.

If a person gets infected despite being vaccinated — we refer to that as a ‘breakthrough’ infection — does that person have the capability of transmitting to another person?” “There have been some studies that are pointing in a very favorable direction,” he said, adding that these studies will have to be corroborated by additional research.

Fauci highlighted two recent studies that looked at a person’s viral load — that is, how much virus he or she has in the body — and transmissibility. One study from Spain, published Feb. 2 in The Lancet, found a direct correlation between viral load and transmissibility. The higher the viral load, the greater the transmissibility of the virus.

That’s in line with what years of research on HIV have shown: there’s a direct link between the viral load in someone’s blood and the likelihood that individual will transmit HIV to a sexual partner, Fauci said.

For SARS-CoV-2, the virus that causes Covid-19, researchers are focused on how much virus is found the nasopharynx, the upper part of the throat behind the nose that’s reached with a long, skinny swab.

https://www.nbcnews.com/

How Does an mRNA Vaccine Work?

The COVID-19 pandemic has brought unusual attention to everything from handwashing to polymerase chain reaction (PCR) tests. As we move into the later stages of this pandemic, though, a different scientific concept has dominated the national conversation: vaccines. The study of the human immune system and how vaccines influence it is complex and sometimes counterintuitive, and the deployment of a new method for immunization based on mRNA has made it all the more confusing.

The two vaccines that have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration are both mRNA vaccines. And since they’re our only hope for ending this pandemic, it’s crucial to understand how they work—and why you should get one.

Vaccines come in a few main forms, but they share the same central goal: equip our immune systems with the tools to handily defeat a pathogen we might encounter in the future. Think of it like a practice round before your body sees the real thing.

The exact way our bodies develop this preemptive immunity depends on the kind of vaccine we’re given. Live-attenuated vaccines provide our cells with a weakened version of a pathogen; protein subunit vaccines give just one part of a bad guy, so immune cells know how to recognize that part of a virus or bacterium. But mRNA (short for messenger RNA) vaccines actually provide our cells with the instructions for making a protein from the pathogen, in essence creating their own practice dummy. Our own cells produce the viral protein specific to, say, SARS-CoV-2, and then our immune system learns to recognize the proteins.

Source: https://www.popsci.com/

Single Dose Nanoparticle Vaccine Efficient To Produce Covid Antibodies

Across the world, health care workers and high-risk groups are beginning to receive COVID-19 vaccines, offering hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use in the U.S. require two doses to be effective, which can create problems with logistics and compliance. Now, researchers reporting in ACS Central Science have developed a nanoparticle vaccine that elicits a virus-neutralizing antibody response in mice after only a single dose.

The primary target for COVID-19 vaccines is the spike protein, which is necessary for SARS-CoV-2’s entry into cells. Both of the vaccines currently authorized in the U.S. are mRNA vaccines that cause human cells to temporarily produce the spike protein, triggering an immune response and antibody production.

Peter Kim and colleagues wanted to try a different approach: a vaccine consisting of multiple copies of the spike protein displayed on ferritin nanoparticles. Ferritin is an iron storage protein found in many organisms that self-assembles into a larger nanoparticle. Other proteins, such as viral antigens, can be fused to ferritin so that each nanoparticle displays several copies of the protein, which might cause a stronger immune response than a single copy.

The researchers spliced spike protein and ferritin DNA together and then expressed the hybrid protein in cultured mammalian cells. The ferritin self-assembled into nanoparticles, each bearing eight copies of the spike protein trimer. The team purified the spike/ferritin particles and injected them into mice. After a single immunization, mice produced neutralizing antibody titers that were at least two times higher than those in convalescent plasma from COVID-19 patients, and significantly higher than those in mice immunized with the spike protein alone. A second immunization 21 days later produced even higher antibody levels. Although these results must be confirmed in human clinical trials, they suggest that the spike/ferritin nanoparticles may be a viable strategy for single-dose vaccination against COVID-19, the researchers say.

Source: https://www.acs.org/

First Antibody Treatment For COVID-19

Scientists in the UK have just recruited the first participants in the world to be part of a new long-acting antibody study. If the treatment is effective, it could give those who have already been exposed to SARS-CoV-2 protection from developing COVID-19.

We know that this antibody combination can neutralise the virus,explains University College London Hospitals (UCLH) virologist Catherine Houlihan. So we hope to find that giving this treatment via injection can lead to immediate protection against the development of COVID-19 in people who have been exposed – when it would be too late to offer a vaccine.”

This might not be the first antibody treatment for COVID-19 you’ve heard of. Outgoing US President Donald Trump was given monoclonal antibodies when he came down with the disease, and in the US two different antibody treatmentscasirivimab and imdevimab – received emergency approval back in November. But those antibody treatments are given to patients with mild or moderate COVID-19, who risk progressing to a severe version of the disease.

In a clinical trial of patients with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalisation or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo,the FDA explained in a press statement when the drugs were approved. This new antibody therapy, called AZD7442 and developed by UCLH and AstraZeneca, is a little different. AZD7442 is a combination of two monoclonal antibodies AZD8895 and AZD1061, which both target the receptor binding domain of the SARS-CoV-2 spike protein.

By targeting this region of the virus’s spike protein, antibodies can block the virus’s attachment to human cells, and, therefore, is expected to block infection,” the team wrote on the US ClinicalTrials.gov website.  “Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector functionin order to decrease the potential risk of antibody-dependent enhancement of disease.”

Antibodies are little Y-shaped proteins that lock on to a particular section – called an antigen – of a virus, bacterium or other pathogen, and either ‘tag‘ it to be attacked by the immune system, or directly block the pathogen from invading our cells. Normal antibodies are produced by your body after an infection, while monoclonal antibodies are cloned in a lab and can be injected into a person already infected, to give the immune system a hand in the fight.

The researchers are hoping that AZD7442 – which is just starting the Storm Chaser study (the name for its phase 3 trial) – provides protection for those that have been exposed to the virus but do not yet have symptoms. Effectively, they’re trying to stop COVID-19 happening in the first place. “If you are dealing with outbreaks in settings such as care homes, or if you have got patients who are particularly at risk of getting severe COVID, such as the elderly, then this could well save a lot of lives,” said University of East Anglia infectious disease expert Paul Hunter.

Source: https://www.sciencealert.com/