How to Use mRNA Technology in Vaccines to Fight Cancer

Until recently, most of the world had never heard of mRNA vaccines. To combat COVID-19, the United States Food and Drug Administration issued emergency use authorization in December 2020 for mRNA vaccines developed by Pfizer-BioNTech and Moderna. While the pandemic brought mRNA vaccines into the limelight, melanoma patient Bobby Fentress had experience with mRNA technology nearly a year prior. mRNA vaccines hold promise for fighting infectious diseases beyond the SARS-CoV-2 virus, including fighting cancer. At age 68, Bobby was an early participant in a clinical trial intended to see whether a vaccine made with mRNA could destroy his cancer cells and prevent recurrence.

Bobby’s story began in 2019. He found an odd bump on his middle finger and assumed it was a wart. After his wife urged him to be seen by a dermatologist, he received a call that he would need a biopsy – which ultimately revealed that he had stage 2c melanoma. Several months later, Bobby had most of his middle finger amputated and was told that there was a 50% possibility that the cancer would reoccur.  That’s when Bobby decided to enroll in a clinical trial with HCA Healthcare’s Sarah Cannon Research Institute in Nashville, Tennessee. He received his first shots of a personalized mRNA vaccine created by Moderna in April 2020. These vaccines are developed from a patient’s specific tumor DNA. The DNA of the tumor is analyzed to determine the differences between the tumor and a patient’s own cells and which proteins might elicit the best immune response. The mRNA vaccine is then developed to instruct the body to make these proteins and stimulate an immune response. Patients such as Bobby then receive a series of these vaccine treatments.

Bobby finished his year of treatment earlier this spring. While it is too early to know if the therapy will work, Bobby’s oncologist, Dr. Meredith McKean, is optimistic.  Immunotherapy has been a game changer for melanoma. With mRNA, the hope is that personalized therapy would offer additional treatment benefit above our standard treatments that we offer for patients broadly. Even for patients like Bobby that had surgery, ten years ago we wouldn’t be able to give him anything but highly toxic therapy options. It’s refreshing to offer a clinical trial like this. While the trial is not yet complete, we have enough data to be hopeful. It’s a very encouraging area that I’m excited about as a provider,” says Dr McKean, associate director of the melanoma and skin cancer research program at Sarah Cannon Research Institute.

https://hcahealthcaretoday.com/

How To Reverse Cell Aging

A team of scientists has found why elderly people are more susceptible to COVID-19 and are working to reverse the aging process of the body’s immune system.

Scientists from the Technion-Israel Institute of Technology say they have found a way to rejuvenate the aging process of the body’s immune system. Prof. Doron Melamed and doctoral student Reem Dowery sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. The results of their work were published this month in the peer-reviewed, online medical journal Blood.
The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and diseases.
B cells do not just disappear. They turn into “memoryB cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That is because the immune response will be fast and robust, and it will eliminate the pathogen, often without the individual knowing he or she had been exposed to it.


Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens, and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.
What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. But this year, they took the discovery another step and figured out a mechanism to override the system.
We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.”

It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells.

Source: http://www.jpost.com/

Simple Blood Test Detects Early Pancreatic Cancer

A test that spots pancreatic cancer from a single drop of blood could improve survival rates. The first blood test for early diagnosis of the hard-to-spot disease, it could be available within monthsPancreatic cancer has the lowest survival rate of the common cancers, with 7.3 per cent of patients alive five years after diagnosis, compared to 58.4 per cent of bowel cancer patients and 85 per cent of breast cancer patients.

The disease is one of the hardest to diagnose early. This is partly because the pancreas — a pear-shaped gland that makes digestive juices and hormones including insulin — is hidden behind the stomach, making it difficult for tumours to be felt or seen on scans. It also doesn’t usually cause symptoms in the early stages — when they do occur, the signs, such as stomach or back pain, weight loss and indigestion, can be vague and easily confused with conditions, such as irritable bowel syndrome.

Treatments include surgery, radiotherapy and chemotherapy but their effectiveness hinges on early diagnosis. Caught early, before the disease has spread to other organs, up to 25 per cent of patients will live for at least five years. If the disease has spread, average survival is two to six months.

The new test, developed by Swedish biotech firm Immunovia and being trialled on 2,000 people at University College London Hospital, and 20 other centres in the U.S., Spain and Sweden, looks for signs of the disease in patient’s blood. These include different levels of around 30 proteins and other compounds identified by the Swedish scientists.

They provide a distinct chemical fingerprint of the disease. The test picks out the compounds using antibodies that latch on to individual chemicals: sophisticated scanning equipment is then used to measure their levels. Previous research shows the test is 96 per cent accurate in spotting people with early-stage pancreatic cancers.

Source: https://immunovia.com/
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Intravenous Immunoglobulins Could Stop Thrombosis after Astrazeneca Vaccination

Some people have developed dangerous blood clots in the brain after receiving the corona vaccination with the AstraZeneca preparation The University Medical Center Greifswald in Germany has now broken down the likely cause of the blood clots. According to Andreas Greinacher, he and his team found special antibodies in the blood of those affected, which are directed against the body’s own blood platelets. These cells play an important role in blood clotting. The antibodies activate the platelets: they clump together, as they normally do to close a wound, and thus form blood clots. The basic problem is therefore an autoimmune reaction.

In Germany, 13 cases of sinus vein thrombosis were reported shortly after an AstraZeneca vaccination, all of which were associated with a lack of blood platelets, i.e. a so-called thrombocytopenia. Around 1.6 million people in Germany were vaccinated. According to Greinacher, the problems that arose shortly after the vaccination are similar to a long-known complication with the administration of another agent, heparin-induced thrombocytopenia, or HIT for short. There, too, antibodies activate platelets so that clots form. In both cases the symptoms appear within 5 to 14 days after administration of the preparation. Greinacher therefore emphasized that the flu-like symptoms that often occur on the day after the vaccination are not a warning signal that a blood clot is developing. But anyone who has a painful leg about five days after the vaccination – as a sign of a deep vein thrombosis – or a severe headache should see a doctor immediately.

The Society for Thrombosis and Hemostasis Research has already published recommendations for doctors based on the Greifswald findings. She assumes that the formation of clots in people with sinus vein thrombosis and thrombocytopenia can be stopped by giving high doses of intravenous immunoglobulins. Greinacher could not answer how reliably this therapy helps those affected. That is not his area of expertise, he said.

Source: https://www.uni-greifswald.de/
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How to Stop Allergies and Autoimmune Disease

We found this absolutely fascinating mechanism of our own bodies that stops the production of rogue antibodies that can cause either autoimmunity or allergies,” senior author, ANU Professor Carola Vinuesa, said. “It’s been known for years that neuritin has a role in the brain and in the nervous system but we found an abundance of neuritin in the immune system and its mechanism – which has never been described in biology. “We have shown it is one of our immune system’s own mechanisms to prevent autoimmunity and allergy and now we have the evidence, we can go on to harness that for treatment.”

The researchers say they set out over five years ago to bridge a knowledge gap on how the immune system works following an educated guess that neuritin might have a regulatory function in stopping allergies and autoimmune disease.

The study, published today in Cell, found neuritin can prevent the production of pathogenic antibodies.

It is an incredible discovery. We saw that in the absence of neuritin there is increased susceptibility to death from anaphylaxis, highlighting its role in the prevention of life-threatening allergies,” first author, ANU researcher Dr Paula Gonzalez Figueroa, said.

For people with allergies, when the immune system overreacts to allergens – like pollen, dust or peanut butter – it produces antibodies called Immunoglobulin E, (IgE). Allergies happen when the body produces excessive IgE in response to otherwise harmless substances, leading to the release of histamine that causes allergic reactions. “We have discovered neuritin prevents excessive formation of IgE that is typically associated with some common forms of allergy and food intolerances,” Professor Vinuesa said.

Many autoimmune diseases are caused or exacerbated by antibodies that go on to destroy our own tissues and cause autoimmune diseases like lupus and rheumatoid arthritis. “There are over 80 autoimmune diseases, in many of them we find antibodies that bind to our own tissues and attack us instead of targeting pathogens – viruses and bacteria,” Dr Paula Gonzalez-Figueroa said. “We found neuritin supresses formation of rogue plasma cells which are the cells that produce harmful antibodies.”

The researchers hope the discovery will now form the basis of new treatments.

Source: https://www.anu.edu.au/

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/

Amazon is now selling COVID-19 tests for customers to use at home

The DxTerity COVID-19 Saliva at-Home Collection Kit detects the presence of the virus but does not confirm immunity or detect antibodies. DxTerity‘s molecular-based PCR test received approval from the Food and Drug Administration last month. The test differs from the quicker and less expensive antigen tests, which use a nasal swab or throat swab to detect the virus.

A single COVID-19 testing kit is listed for $110, and a 10-pack bundle is available for $1,000.

Test takers must spit into a tube provided by the kit. The saliva sample is then inserted into a plastic bag and packed back into the box for shipment to one of DxTerity‘s laboratories certified by the Clinical Laboratory Improvement Amendments. Customers are also granted prepaid express return shipping with the test and should expect to receive results within 24 to 72 hours of sample receipt at the laboratory. DxTerity’s test is currently the only COVID-19 testing kit on Amazon.

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We have demonstrated the reliability and quality of our COVID-19 testing solution with big business and now we want to expand access to customers at home and small businesses,” said Bob Terbrueggen, founder and CEO of DxTerity, when he first announced the collaboration with the company last month. “Amazon is the perfect partner for expanding access to millions of U.S. customers.”

The test may not be valid for all travel purposes because sample collection is unsupervised, according to the product description. The Centers for Disease Control and Prevention recommends saliva specimens should be collected under supervision.

Amazon joins other retail giants in offering at-home COVID-19 saliva tests. Costco offers both regular and those approved for travel requirements to Hawaii, Bermuda and some other destinations for $129.99 and $139.99, respectively. However, the test has several dozen one-star reviews, with most complaining about delayed shipping and poor customer service from provider AZOVA.

Source: https://eu.usatoday.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/

Innovative Universal Flu Vaccine

For epidemiologists, the COVID-19 pandemic has greatly intensified their long-standing nightmare about another virus: the emergence of a new and deadly strain of flu. A universal flu vaccine, effective against any strain of the influenza virus that can infect humans, could protect us from this peril, but progress has been slow. A novel concept for one universal vaccine candidate has now passed its first test in a small clinical trial, its developers report today in Nature Medicine.

Seasonal flu vaccines induce antibodies against the “head” (slate) of the influenza surface protein hemagglutinin, but a new universal vaccine triggers antibodies (fragments of them shown in gray) that bind to the stalk (light blue) portion

This is an important paper,” says Aubree Gordon, an epidemiologist at the University of Michigan School of Public Health who studies influenza transmission and vaccines.

The influenza virus rapidly accumulates mutations and easily “reassorts,” or swaps, genes between strains, creating variants that can dodge any past immunity people had acquired naturally or from vaccines. That’s why a new flu vaccine must be developed each year. Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does reassort, or mutate, frequently, which allows new viral strains to dodge any immune memory and forces flu vaccinemakers to prepare new formulations each year, with updated HAs.
In the trial, 51 participants received the various vaccines and their antibodies were compared with those of 15 people who received placebos. A single shot of vaccine with chimeric HA inactivated viruses, the researchers report, “induced remarkably high antistalk antibody titers.”

Source: https://www.sciencemag.org/