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Does the Novel Coronavirus Mutate?

By Shlomo Maital

     Writing in today’s New York Times, Nathaniel Lash and Tala Schlossberg try to answer the key question, does the novel coronavirus mutate? If so, how and when?

   Here is why it is important for us to know this.   The pandemic crisis will end only when we have a vaccine, produced in billions of doses. The vaccine will work by stimulating the body to produce antibodies that neutralize the virus by binding to it in a very specific way. If the virus can mutate to defeat the vaccine, then the vaccine will not stop working. The key is the “spike protein” – the protein the virus makes that penetrates the cell walls and lets the virus invade (and kill) it. Those are the spikes you see in the graphic illustrations of corona. Vaccines can defeat the spike.

   Here is what the authors of the article have found:

   “Among the thousands of samples of the long strand of RNA that makes up the coronavirus, 11 mutations have become fairly common. But as far as we know, it’s the same virus infecting people all over the world, meaning that only one “strain” of the virus exists, said Peter Thielen, a molecular biologist with the Johns Hopkins Applied Physics Laboratory.   Only one of those common mutations affects the “spike protein,” which enables the virus to infect cells in the throat and lungs. Efforts to produce antibodies that block the spike protein are central to many efforts to develop a vaccine. Since the spike protein has changed little so far, some scientists believe that’s a sign that it can’t alter itself very much and remain infectious.”

   So – we have a small piece of good news. The measles vaccine, for instance, was developed in 1950. And it is still effective. Measles hasn’t mutated in a manner that neutralizes the vaccine. Evolution is powerful – but apparently it cannot surmount EVERY obstacle. So hopefully the same will apply to the COVID-19 vaccine – and we will bid this insidious deadly enemy good-bye, with an effective vaccine… until the next one.

A Vaccine is Coming – from Pittsburgh

By Shlomo Maital

Univ. of Pittsburgh “Cathedral of Learning”

   Before the good news about a COVID-19 vaccine – a piece of history.

     In 1947, native New Yorker Jonas Salk accepted an appointment to the University of Pittsburgh School of Medicine. In 1948, he undertook a project funded by the National Foundation for Infantile Paralysis to determine the number of different types of poliovirus. Salk saw this was a golden opportunity to extend this project towards developing a vaccine against polio. He built a research team and devoted himself to this work for the next seven years. The field trial set up to test the Salk vaccine involved 20,000 physicians and public health officers, 64,000 school personnel, and 220,000 volunteers.   Over 1.8 million schoolchildren took part in the trial.

    On March 26, 1953, Salk announced on a national radio show that he had successfully tested a vaccine against poliomyelitis, the virus that causes the crippling disease of polio. In 1952—an epidemic year for polio—there were 58,000 new cases reported in the United States, and more than 3,000 died from the disease. Dr. Salk was celebrated as the great doctor-benefactor of his time.

   Fast forward.   A press release from the NIH: https://www.nih.gov/news-events/nih-research-matters/microneedle-coronavirus-vaccine-triggers-immune-response-mice

   “After the identification of SARS-CoV-2, the genome sequence of the new coronavirus was rapidly released to the public by scientists in China. Several weeks later, National Institute of Health-funded scientists produced a detailed picture of the part of the virus, called the spike protein, that allows it to infect human cells. This spike protein is currently the target of several vaccine development efforts. And we see the graphic version of the corona ‘spikes’ everywhere…

   “Researchers led by Drs. Louis Falo, Jr. and Andrea Gambotto from the University of Pittsburgh have been working to develop vaccines for other coronaviruses, including the one that causes Middle East Respiratory System (MERS). They adapted the system they had been developing to produce a candidate MERS vaccine to rapidly produce an experimental vaccine using the SARS-CoV-2 spike protein.

   The team developed a method for delivering their MERS vaccine into mice using a microneedle patch. Such patches resemble a piece of Velcro, with hundreds of tiny microneedles made of sugar. The needles prick just into the skin and quickly dissolve, releasing the vaccine. Since the immune system is highly active in the skin, delivering vaccines this way may produce a more rapid and robust immune response than standard injections under the skin.

   “When delivered by microneedle patch to mice, three different experimental MERS vaccines induced the production of antibodies against the virus. These responses were stronger than the responses generated by regular injection of one of the vaccines along with a powerful immune stimulant (an adjuvant). Antibody levels continued to increase over time in mice vaccinated by microneedle patch—up to 55 weeks, when the experiments ended.

   “Using knowledge gained from development of the MERS vaccine, the team made a similar microneedle vaccine targeting the spike protein of SARS-CoV-2. The vaccine prompted robust antibody production in the mice within two weeks.

   “The vaccinated animals haven’t been tracked for enough time to see if the long-term immune response is equivalent to that observed with the MERS vaccines. The mice have also not yet been challenged with SARS-CoV-2 infection. However, the findings are promising in light of results from the similar MERS vaccine.

   “The components of the experimental vaccine could be made quickly and at large-scale, the researchers say. The final product also doesn’t require refrigeration, so it could be produced and placed in storage until needed. The team has now begun the process of obtaining approval from the U.S. Food and Drug Administration to launch a phase 1 trial within the next several months.

   “Much work still needs to be done to explore the safety and efficacy of this candidate vaccine. “Testing in patients would typically require at least a year and probably longer,” Falo says. “This particular situation is different from anything we’ve ever seen, so we don’t know how long the clinical development process will take.”

OK – it works in mice. Now for humans. A vaccine is on the way – and it may emerge again from Univ. of Pittsburgh.

 

   

 

 

 

 

What Do We NOT Know?!

By Shlomo Maital

  After more than four months of nonstop news/debate/discussion around COVID-19, it is astonishing how much we do not know. And as the saying goes, what you don’t know that you don’t know — is the worst; it can literally kill you.

   So here is my attempt to list, what it is we don’t know, that we NEED to know, about this tiny virulent enemy and hopefully, scientists are working on it.

  • For those who get COVID-19 and recover, are they immune? For life? For a short time? How long does the immunity last?
  • Like many viruses, can this novel coronavirus mutate quickly and attack those who contracted an older version? Are COVID-19 cases in the US characterized by the same genetically-identical virus as say in China, or different? If so, how different? And does it matter?
  • Intubation: Are we in too much of a hurry to put people on intubation (ventilators)? If such a small percentage of those intubated, survive, should we rethink this? And how different are the various kinds of ventilators (those used by anesthetists, oxygen ventilators, standard ventilators, etc.)?
  • Why are the death rates (those who die from COVID-19, as a % of those who are seriously ill, or in general % of those who contract the virus) different, radically, between one country and another?   How much of this is due to ICU expertise?
  • How exactly does COVID-19 spread?   As aerosol (tiny droplets that hang in the air for hours?)   As big droplets (that fall to the ground fairly quickly)?  
  • Are there drugs proven to be effective against COVID-19? What about the recently-approved anti-influenza drugs? Xofluza, Tamiflu, Relenza, Rapivab ? And, of course, hydroxychloroquine? (which seems to have severe heart side-effects among some patients).
  • Why are African-Americans more afflicted than Caucasians? Men more than women?
  • Will there be a second wave? And a third? How will we know in time?
  • How soon will we have a proven vaccine, and how quickly can doses be produced, to inoculate billions of people? How much will it cost? Can it be provided for free? How can the many companies working on a vaccine, in many countries, work together, to save time and save lives?
  • What countries have managed the COVID-19 crisis best, and what can be learned from them? There have been many variations on lockdown, ranging from easy (Sweden) to draconian (China, Singapore).   Which works best?
  • Somewhere, as we speak, a new virus is brewing and mutating somewhere; this is not the last pandemic. Can we organize a world-spanning organization (broader in span than WHO, with far more resources) that will be ready to tackle the next pandemic quickly and efficiently? With massive resources?  

 

I’m certain there are a thousand more things we do not know. Add your own questions… for each question above, there are multiple answers online, and many of them are fake or conspiratorial.   This simply adds to the fog.

 

The Coronavirus Vaccine Will Be French:

Meet Prof. Frederick Tanji

By Shlomo Maital

Prof. Frederick Tanji

Louis Pasteur wa born on December 27, 1822 –and died on September 28, 1895. He was a French biologist, microbiologist and chemist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization. He made remarkable breakthroughs in the causes and prevention of diseases, and his discoveries have saved many lives ever since. He reduced mortality from puerperal fever and created the first vaccines for rabies and anthrax.” The Pasteur Institute in Paris, named after him, is a world leader in this field.

   Fast forward. Prof. Frederick Tanji is a senior professor at the Pasteur Institute in France and the head of the Department of Virology at the National Institute of Scientific Research (CNRS). He works day and night on developing a vaccine against a corona virus, and is one of the top candidates to get to the finish line first.

According to press accounts, “Tanji’s development team received € 4.3 million in funding to start clinical trials for the corona vaccine he developed, which, like others developed at the institute, is based on measles vaccine. “I developed a measles vaccine given to every baby born, which is effective and safe,” Tanji explains. “All the vaccine makers in the world know how to produce this vaccine in large quantities – which is very important. It’s also very cheap. This vaccine can be used as a (vector) basis for the Corona vaccine. I have engineered the measles virus genome so pathogenic sequences can be added to it. Like other viruses. That’s what we’re doing now with the Corona virus. “

“Tanji’s method – based on measles vaccine – has already been applied to other vaccines that have undergone clinical trials and some are already in production, and are designed to prevent Zika’s disease, Lassa fever, 1SARS, and MERS, “so we already have experience developing corona vaccine vaccines “, Says Tanji.

If Tanji succeeds, we need to thank the Chinese. “The speed at which vaccine development researchers came to be due in part to the early and rapid Chinese effort to sequence the genome of the new virus. China shared the genetic information in early January, allowing distance groups around the world to grow and investigate a live virus.”

Tanji wants the vaccine to be produced and sold at cost.

Tanji thinks human behavior will have to change radically post-COVID-19. “Social behavior will have to change, and we will have to significantly reduce travel. 4 billion people are flying every month – half the world’s population, that’s crazy. It transmits diseases. The economy needs to change.”

A Vaccine Is On The Way – Soon?

By Shlomo Maital

Today’s Jerusalem Post daily paper, published in Jerusalem, brings some much-needed good news about progress in creating a vaccine against COVID-19.

The report notes:

A team of Israeli researchers says that they are days away from completing the production of the active component of a coronavirus vaccine that could be tested on humans as early as June 1. “We are in the final stages and within a few days we will hold the proteins – the active component of the vaccine,” Dr. Chen Katz, group leader of MIGAL’s biotechnology group, told The Jerusalem Post.   In late February, MIGAL [The Galilee Research Institute] committed to completing production of its vaccine within three weeks and having it on the market in 90 days. Katz said they were slightly delayed because it took longer than expected to receive the genetic construct that they ordered from China due to the airways being closed and it having to be rerouted.”

     (Note: the ‘genetic construct’ from China, is simply the RNA ribonucleic acid that defines COVID-19 — shame that cancellation of flights from China to Israel caused the delay – every day counts!).

   “As a reminder, for the past four years, researchers at MIGAL scientists have been developing a vaccine against infectious bronchitis virus (IBV), which causes a bronchial disease affecting poultry. The effectiveness of the vaccine has been proven in preclinical trials carried out at the Veterinary Institute.”

   Amazing that chickens, maybe, and their vaccine can help save human lives?

   The report continues:   “Our basic concept was to develop the technology and not specifically a vaccine for this kind or that kind of virus,” said Katz. “The scientific framework for the vaccine is based on a new protein expression vector, which forms and secretes a chimeric soluble protein that delivers the viral antigen into mucosal tissues by self-activated endocytosis, causing the body to form antibodies against the virus.”

   What does this mean? Basically: The vaccine helps the body produce a key protein able to penetrate the cells infected by COVID-19 in the throat and lung mucous. How does it penetrate?   Endocytosis is “the process of actively transporting molecules into the cell by engulfing it with its membrane.” This helps the cell produce antibodies that kill the virus, before it can kill the cell and reproduce, creating millions of new viruses that spread through the lungs.

     “In preclinical trials, the team demonstrated that the oral vaccination induces high levels of specific anti-IBV antibodies, “ a MAGAL expert said.

     A worldwide race is on, to develop an effective safe COVID-19 vaccine.   Whoever wins, humanity will be the big winner.   This is one race that can benefit everyone, even the spectators.

Conquering Ebola:  How They Did It

By Shlomo Maital

ebola

  As usual, the deaths and suffering from Ebola got far more media attention than the team of brave and creative people who have conquered it. (Global New York Times, Aug. 1-2, 2015, p. 6)

  It started in Canada.  Researchers at the Public Health Agency of Canada created an experimental vaccine (yup – that’s right,  a government agency!).  They took a piece of the virus’s covering and combined it with an animal virus (vesicular stomatitis virus), to set off an immune reaction against Ebola. I can only imagine the risks involved in working with such a virulent and often-fatal virus, in a lab. 

   A private biopharm company, NewLink Genetics, based in Ames Iowa, licensed the breakthrough vaccine, and last November, Merck, Big Pharma, did too. 

   The clinical trial was crucial.  It was led by the WHO,  Guinean Health Ministry, Doctors Without Borders, Epicentre Research and the Norwegian Institute of Public Health.

    Among the clinical trial innovations: a beer-keg-shaped storage device, the Arkteck, that kept the vaccines at minus 80 degrees without electricity, so that they could be transported.   The keg was invented by Global Good, a collaboration between an investment company Intellectual Ventures and Bill & Melinda Gates’ Foundation.

     None of those vaccinated in the trial,  about 4,000 people, contracted the disease, even when exposed to it.  The main use will be to vaccinate medical workers exposed to Ebola, rather than huge populations.

     What do we learn from this?  Simple.   To tackle a really hard problem, you need to put together global collaborations – governments, NGO’s, companies big and small, volunteers, African governments,   and they need to work together seamlessly, each contributing his or her own creativity and energy.  In the end, courageous lab workers did the job, but it took the whole ‘village’ to save a child, or many many of them. 

    The whole ebola virus vaccine eco-system deserves a Nobel.

Scientists Who Endanger Their Lives:  The Case of Ebola

By Shlomo  Maital    

ebola

   Scientific papers published in Science rarely involve heroism, drama, and life-threatening courage.   This one does:

Gire, SK, Goba, A et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science, 2014, online.

    Here is the story, as described in a dry press release by Harvard:

     “ n response to an ongoing, unprecedented outbreak of Ebola virus disease (EVD) in West Africa, a team of researchers from the Broad Institute and Harvard University, (MIT-Harvard),  in collaboration with the Sierra Leone Ministry of Health and Sanitation and researchers across institutions and continents, has rapidly sequenced and analyzed more than 99 Ebola virus genomes. Their findings could have important implications for rapid field diagnostic tests. The team reports its results online in the journal Science.”

       The research was led by Broad Institute researcher Pardis Sabeti, Augustine Goba, Director of the Lassa Laboratory at the Kenema Government Hospital in Sierra Leone, and Stephen Gire, first author,  a research scientist in the Sabeti lab at the Broad Institute and Harvard.  The team  shipped samples back to Boston, and then  20 people worked around the clock.   In one week:  they decoded gene sequences from 99 Ebola samples!  This is truly amazing. 

        What the team did was to act rapidly to collect samples of Ebola from a Sierra Leone hospital last April, when the outbreak began, and then gathered additional samples as the virus spread and mutated.  They did this under life-threatening conditions, especially those on the ground on-site, because at the time there was insufficient protective gear for hospital workers, and some indeed died. 

       They gathered 99 samples of Ebola in all. Then they decoded the genome of each sample.  This was unprecedented in its speed.   What they found was important.  The Ebola virus has only 7 genes (!) compared to the human genome, comprising more than 20,000 genes.  Like all viruses, Ebola penetrates the human cell and commandeers its DNA mechanism, to make more viruses rather than human DNA.  Ebola is fatal in 52 per cent of all cases.

      The Broad Institute researchers found that Ebola initially spread from an animal to a human.  BUT —  from then on, it ONLY spread among humans.  The initial call to avoid mangos and meat was uncalled for.  And like all viruses, they found that the virus evolved and mutated very quickly in humans.  So, we are in a race, between ‘brilliant’ humans with huge brains, and ‘stupid’ viruses with only 7 genes ..and at the moment, the viruses seem to be winning. 

   I salute the courageous scientists and their assistants on-site, for risking their lives to help save the lives of others.  Sometimes, not often, science is life-threatening,  and quickly, life-saving. 

     In this space, I’ve been fiercely critical of Big Pharma, which rips us off by charging scandalously high prices for drugs with minimal impact.  But for once,  Big Pharma is doing the right thing.   GSK Glaxo Smith Kline is helping the U.S. National Institutes of Health to develop an Ebola vaccine.  Only GSK’s huge productive capacity can do this quickly enough to combat the spread of Ebola. 

    

 

 

 

 

 

By Shlomo  Maital    

   Scientific papers published in Science rarely involve heroism, drama, and life-threatening courage.   This one does:

Gire, SK, Goba, A et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science, 2014, online.

    Here is the story, as described in a dry press release by Harvard:

     “ n response to an ongoing, unprecedented outbreak of Ebola virus disease (EVD) in West Africa, a team of researchers from the Broad Institute and Harvard University, (MIT-Harvard),  in collaboration with the Sierra Leone Ministry of Health and Sanitation and researchers across institutions and continents, has rapidly sequenced and analyzed more than 99 Ebola virus genomes. Their findings could have important implications for rapid field diagnostic tests. The team reports its results online in the journal Science.”

       The research was led by Broad Institute researcher Pardis Sabeti, Augustine Goba, Director of the Lassa Laboratory at the Kenema Government Hospital in Sierra Leone, and Stephen Gire, first author,  a research scientist in the Sabeti lab at the Broad Institute and Harvard.  The team  shipped samples back to Boston, and then  20 people worked around the clock.   In one week:  they decoded gene sequences from 99 Ebola samples!  This is truly amazing. 

        What the team did was to act rapidly to collect samples of Ebola from a Sierra Leone hospital last April, when the outbreak began, and then gathered additional samples as the virus spread and mutated.  They did this under life-threatening conditions, especially those on the ground on-site, because at the time there was insufficient protective gear for hospital workers, and some indeed died. 

       They gathered 99 samples of Ebola in all. Then they decoded the genome of each sample.  This was unprecedented in its speed.   What they found was important.  The Ebola virus has only 7 genes (!) compared to the human genome, comprising more than 20,000 genes.  Like all viruses, Ebola penetrates the human cell and commandeers its DNA mechanism, to make more viruses rather than human DNA.  Ebola is fatal in 52 per cent of all cases.

      The Broad Institute researchers found that Ebola initially spread from an animal to a human.  BUT —  from then on, it ONLY spread among humans.  The initial call to avoid mangos and meat was uncalled for.  And like all viruses, they found that the virus evolved and mutated very quickly in humans.  So, we are in a race, between ‘brilliant’ humans with huge brains, and ‘stupid’ viruses with only 7 genes ..and at the moment, the viruses seem to be winning. 

   I salute the courageous scientists and their assistants on-site, for risking their lives to help save the lives of others.  Sometimes, not often, science is life-threatening,  and quickly, life-saving. 

     In this space, I’ve been fiercely critical of Big Pharma, which rips us off by charging scandalously high prices for drugs with minimal impact.  But for once,  Big Pharma is doing the right thing.   GSK Glaxo Smith Kline is helping the U.S. National Institutes of Health to develop an Ebola vaccine.  Only GSK’s huge productive capacity can do this quickly enough to combat the spread of Ebola. 

Breakthrough:  Vaccine Against Cancer!

by Shlomo Maital

cancer vaccine

   Cancer immunology [use of the body’s own immune system to kill cancer cells] has been chosen as the “Breakthrough of the Year” by the editors of Science. A fascinating report was published in the December 20 issue. (This blog is longer than usual, because the topic is so important).

   For example: According to the U.S. National Institutes of Health: The photo shows an aspirin-sized disk, the first therapeutic cancer vaccine implanted beneath the skin. “We know it can eradicate melanoma in mice—the deadliest form of skin cancer—with impressive efficacy . Now, it’s being tested in human trials.”

One day, hopefully, chemotherapy may be replaced by immunotherapy. Instead of poisoning cancer (and our own body), we may be able to trick cancer cells, which are good at defeating the body’s own T-cell immune system, and enable our T-cells to kill cancer cells before they become tumors or even after.

What is the science here? According to the NIH, vaccines prevent illnesses, like smallpox, by introducing dead or weakened germs, to teach the body to create antibodies if it does appear. We already have vaccination against the human papilloma virus (HPV)—a powerful way to prevent cervical cancer. The new anti-cancer vaccines work differently. They’re given to patients who have already been diagnosed with cancer. Once given they “behave like traditional vaccines—by teaching the immune system how to seek out and destroy a target—in this case, a tumor. “

“ A couple of cancer vaccines have already been approved by the FDA. However, producing these vaccines is typically a cumbersome, time-consuming, and expensive process. First, immune cells are taken from a patient. The cells are modified and reprogramed in the lab, and then they are injected back into the patient. In the vaccines approved to date, this elaborate production line has extended patient life—but only slightly. And so, some researchers began to look for a simpler, and perhaps more effective, way to make therapeutic cancer vaccines. About four years ago, an NIH-funded, multidisciplinary team based in Boston and Cambridge came up with an approach that would modify and reprogram patients’ immune cells—inside the body, not in a lab!! The team first developed a porous polymer implant, made from the same material as biodegradable sutures and meshes. Then they infused the disk with a collection of three immune stimulants that recruit the immune cells, activate them, and imprint them with a chemical signature of the tumor that is targeted for destruction.

“The first of the three immune stimulants is a drug called leukine (also known as GM-CSF), which summons millions of dendritic cells, key immune cells, to enter the implant. The second is DNA that mimics viral and bacterial DNA and sends a danger signal that activates these cells. The third ingredient is the personalized part of the recipe: a combination of proteins made from the patients’ own tumor. It gives the dendritic cells the unique signature of that person’s tumor, which they share with the warrior T-cells. The “educated” T-cells are then primed to hunt and obliterate the tumor.”

The new approach is metaphorically like training cancer-killer cells to a) spot cancer, and b) kill it, by first teaching them to recognize the enemy and then, giving them ‘martial arts’ skills to destroy it.

Some of the most advanced work in the world on cancer immunology is done in my country, Israel. Prof. Leah Eisenbach, at the Weizmann Institute, Rehovot, has done breakthrough work. A company known as Compugen has developed antigens proven useful against cancer, and sold two of them for hundreds of millions of dollars to Bayer.

We know today that there are more than 120 different types of cancer. Each requires its own variant of chemotherapy. While survival rates have risen enormously, there has to be a better way than ‘tailored poison’. There is. Immunotherapy may point the way. If you know someone who has cancer, or whose loved ones have it, draw their attention to this new breakthrough. There is definitely hope, and the progress may be relatively rapid.

 

   

Blog entries written by Prof. Shlomo Maital

Shlomo Maital

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