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Posts tagged ‘Dr. Vincent Racaniello’

COVID-19 – It’s Everywhere . . Will an Early Vaccine for COVID-19 Be Safe?


Will an Early Vaccine for COVID-19 Be Safe?

by

Columbia University Professor Emeritus, Dr. David Figurski

presented by

Donna O’Donnell Figurski

(Disclaimer: The World Health Organization <WHO> has officially named the new coronavirus as SARS-CoV-2 and the disease it causes as COVID-19. Because the majority of people, including much of the press, commonly refer to the virus as “COVID-19,” to avoid confusion I use COVID-19 as the name of the virus in these posts.)

 

David Figurski

David H. Figurski, Ph.D & Survivor of Brain Injury

There is intense pressure from this Administration for any good news that might bolster its re-election chances. The government’s own FDA (Food and Drug Administration) might shorten the three required clinical trials that are key to proving the safety and efficacy of any vaccine before it’s approved for use by the public.

There is good reason to be concerned that government officials from this Administration might approve short-cuts to well-established scientific requirements because they want to speed things up. Both the FDA and the CDC (Centers for Disease Control & Prevention), two government agencies I have always trusted, have already bowed to political pressure from this Administration. The FDA approved hydroxychloroquine use for COVID-19 and later rescinded its approval when the drug was found to be ineffective against COVID-19 and to cause some dangerous side-effects in some people. The CDC, after feeling pressure from the Administration, revamped its back-to-school guidelines.

twiv-300x225

Dr. Vincent Racaniello – Columbia University virologist

Drs. Vincent Racaniello (virologist, Columbia U., host of the TWiV <This Week in Virology> podcasts), Brianne Barker (immunologist, Drew U.), and Rich Condit (retired virologist, Professor Emeritus, U. of Florida) discuss this issue in the TWiV podcast #631 of June 25, 2020. I urge you to listen to minutes 4:00-9:00. These three scientists talk about the importance of impartial and uncorrupted science in driving vaccine development and approval.

Also, an article about this issue can be found in the July 29, 2020, issue of HuffPost.

VaccineA legitimate way for the large Phase III clinical trial to end early is when the benefit is obvious. For example, if a vaccine candidate were given to 20,000 people and a placebo were given to another 20,000 people, the efficacy of the vaccine would be obvious (and statistically sound) if several hundred people in the placebo group became sick, while no person in the vaccine group became sick. Such an obvious result is exceedingly rare, and so, since it normally takes about eight months to do a Phase III clinical trial, if all goes well, we probably won’t have a confidence-inspiring vaccine until 2021.

Stay Safe and Healthy!

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COVID-19 – It’s Everywhere . . . Interview with Dr. Anthony Fauci

Dr. Anthony Fauci – an interview by Drs. Vincent Racaniello and Rich Condit, virologists

by

Columbia University Professor Emeritus, Dr. David Figurski

presented by

Donna O’Donnell Figurski

 

(Disclaimer: The World Health Organization <WHO> has officially named the new coronavirus as SARS-CoV-2 and the disease it causes as COVID-19. Because the majority of people, including much of the press, commonly refer to the virus as “COVID-19,” to avoid confusion I use COVID-19 as the name of the virus in these posts.)

David H. Figurski, Ph.D & Survivor of Brain Injury

If you believe in science and facts, this 36-minute podcast will be a treat and essential listening. It was recorded on July 16, 2020, and posted on July 17. (Note: The link is for the page that has all the TWiV podcasts. Make sure you are listening to #641.)

Dr. Vincent Racaniello, a virologist, was my colleague in the Department of Microbiology & Immunology at Columbia University. He does a podcast on viruses called TWiV (This Week in Virology).

Dr. Vincent Racaniello – Columbia University virologist

Vincent, Rich Condit (a retired virologist from the University of Florida), and Dr. Fauci (Director of the National Institute of Allergy and Infectious Diseases) discuss COVID-19 and the pandemic. Among the topics discussed are the paths of infection, symptoms, testing, re-opening schools, fatality rate, immunity, and vaccines.

 

 

Normally, the TWiV scientists make their discussion understandable to non-scientists. But, these three scientists were working against a time-constraint, and they sometimes used terms that some of you may not be familiar with. To help you, I’ve made a glossary. The order of the terms in the list is based on the time in the podcast when the term is first used (noted in parentheses).

Dr. Anthony Fauci 071920

Director of the National Institute of Allergy and Infectious Diseases (NIAID)

Dr. Fauci was also interviewed for 64 minutes in 2013 by Vincent and Rich (TWiV #219).

 

Glossary provided by Dr. Figurski for easier listening.

glossary

PCR-able (2:52) – based on the PCR (polymerase chain reaction) test, which is a very sensitive test for the RNA chromosome (or a chromosomal RNA fragment) of the virus

fomite (3:11) – an infectious object or material

viral load (4:05) – the number of viruses

cycle threshold (4:27) – the PCR test is based on a number of amplification cycles to see a signal; the number of amplification cycles needed is related to the number viruses present; the higher the number of cycles needed, the lower the number of viruses present

nucleotides (5:05) – the building blocks for the viral RNA; the RNA chromosome of COVID-19 is made up of about 30,000 nucleotides

BSL-3 lab (5:12) – a bio-safety level 3 lab has containment and safety precautions that allow scientists to work with microbes thought to be dangerous

antigen (11:47) – a substance that stimulates the production of antibodies to itself; infection with COVID-19 leads to the body’s production of anti-COVID-19 antibodies; in the COVID-19 test discussed here, viral antigens (probably viral proteins) are used to bind to anti-COVID-19 antibodies to detect them; the presence of anti-COVID-19 antibodies is an indication that a person is now infected with COVID-19 or was infected in the past

systemic infection (13:21) – infection of other organs – not just infection of the lungs

systemic sequelae (13:23) – symptoms of infection in other organs

viremia (13:32) – the presence of virus in the blood; because the blood goes to all organs, a viremia allows the virus to reach other organs and can lead to a systemic infection

endothelium (14:22) – the layer of cells that lines organs and vessels

SARS (15:18) – the first SARS (Severe Acute Respiratory Syndrome) pandemic of 2003 – also caused by a coronavirus

MERS (15:21) – Middle East Respiratory Syndrome – another earlier and limited pandemic caused by a coronavirus

sero-prevalence (16:04) – the fraction of people in a population who are positive for antibodies to COVID-19; antibody positivity is an indication that a person is now infected with COVID-19 or was infected in the past

herd immunity (16:28) – immunity of the population by infection or by a vaccine; when people are infected (and recover if they have symptoms), they become immune; if enough people are immune, “herd immunity” has been achieved without a vaccine; the virus has few people to infect productively, and its spread slows to almost nothing; estimates are that 70-80% of the population must become immune to protect the population

Moderna vaccine (20:55) – the company Moderna teamed up with Dr. Fauci’s group and seems to be having some good success so far in phase I and phase II clinical trials (of three phases, see below); instead of the standard method of using a viral protein or several viral proteins to stimulate the production of neutralizing antibodies (see below), the Moderna vaccine uses a brand new technology based on the mRNA (see below) for the viral protein, a method that has never before been used to produce a vaccine

clinical trials – clinical development of a vaccine is a three-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. (From the CDC)

mRNA (20:57) – messenger RNA; in cells, the genetic code for the production of proteins resides in the chromosomes, which are made of the nucleic acid DNA; that code is read and translated into the proteins (the machines of the cell) by the cell’s protein factories – the ribosomes; because the ribosomes need to get the code from the DNA, the messenger RNA (mRNA) comes into play; (RNA is a nucleic acid very closely related to DNA); a protein-machine copies the DNA’s code into mRNA, which then brings the code to the protein factory, where it is read and the protein is made

neutralizing antibody (21:09) – an antibody that blocks infection by the virus; for COVID-19, an antibody that inactivates the spike protein of the virus (see below) is a neutralizing antibody

convalescent serum (21:17) – serum from the blood of patients who have recovered from COVID-19; the serum contains the antibodies

spike protein (21:51) – a protein of COVID-19; important because it’s needed for the virus to bind tightly to the ACE2 (22:19) (angiotensin converting enzyme 2) protein that’s on the surface of lung cells; the binding is needed for the virus to gain entry to the cell and start the infection; a target for some vaccines; antibodies that inactivate the spike protein are called “neutralizing antibodies”

hemagglutinin, neuraminidase (22:39) – surface proteins of influenza virus needed for infection and for the release of progeny virus, respectively; antibodies to these proteins (usually to hemagglutinin) are the basis of the vaccine for influenza virus

monoclonal antibody (27:29) – the body’s collection of antibodies is produced by a population of B cells; each B cell produces one specific antibody; if a B cell can be cloned and cultured away from the population of B cells, then that culture will produce only that one specific antibody (for example, an anti-spike protein antibody), also called a “monoclonal antibody”

pathogen (28:17) – infectious agent (virus, bacterium, or parasite) that causes disease

NIAID (31:40) – National Institute of Allergy and Infectious Diseases; a part of the National Institutes of Health (NIH); the NIAID is headed by Dr. Fauci

 

Stay Safe and Healthy!

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(Photos compliments of contributor.)

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COVID-19 – It’s Everywhere . . . Immune Response, Vaccine Development, & Asymptomatic Infections

New Info for COVID-19: Immune Response, Vaccine Development, & Asymptomatic Infections

by

Columbia University Professor Emeritus, Dr. David Figurski

presented by

Donna O’Donnell Figurski

(Disclaimer: The World Health Organization <WHO> has officially named the new coronavirus as SARS-CoV-2 and the disease it causes as COVID-19. Because the majority of people, including much of the press, commonly refers to the virus as “COVID-19,” to avoid confusion I use COVID-19 as the name of the virus in these posts.)

David H. Figurski, Ph.D & Survivor of Brain Injury

I have taken a 119-minute podcast on COVID-19 by a virologist and reduced it to the 21 minutes you probably want to hear the most. This long post looks scary, but it’s actually very easy to read and makes the 21 minutes readily understandable.

Dr. Vincent Racaniello, a virologist at Columbia University, was my colleague in the Department of Microbiology & Immunology. He does a podcast on viruses, called TWiV (This Week in Virology). Since March 13th, when we started staying home and taking precautions to minimize the pandemic, Vincent has released over 40 podcasts, nearly all of which are about COVID-19.

TWiV is unique because the host, Vincent, does research on and lectures about viruses. In addition to his being a scientist, his podcasts always have a panel of PhDs, sometimes as many as five people (two more virologists, an immunologist, a parasitologist, and a former student – now a science reporter). The discussions are great and done with a non-scientist-audience in mind. TWiV is known worldwide and attracts tens of thousands of listeners every month. However, the TWiV podcasts are long (~1-2.5 hours), so I listen and tell you the minutes to listen to hear information that I think you’ll want to know.

This post is about TWiV #631, which was posted on June 25, 2020. (Note: The TWiV link is for all the podcasts. Be sure you listen to #631.)

TWiV podcast #631 is 119 minutes long, but I have selected ~21 minutes you may want to hear. The topics you’ll hear discussed are the following: the value of the safety precautions, the need for free and extensive testing, the unknowns of the immune response, the timetable for vaccine development (at least eight more months), and the role of age in symptomatic and asymptomatic infections.

I have broken down #631 into segments defined by the minutes I chose for you to listen to. (The last half of the podcast was spent answering questions from listeners. While much good information is in this section, I emphasized the parts you probably want to hear the most.)

Podcast #631 features a discussion by three scientists: Vincent (virologist, professor, Columbia U.), Rich Condit (virologist, Professor Emeritus, U. of Florida), and Brianne Barker (immunologist, professor, Drew U.). The scientists usually make sure their discussion is understandable to their generally non-scientist listeners, but I found that they occasionally used terms that may be unfamiliar to you. Therefore, I have provided a glossary in the segment in which the term is first used.

TWiV #631
Segment 1
Minutes 3:10-9:10
The cavalier attitude of some people to safety precautions; the spike of new cases in the US; the toxic mixture of politics and science; the 172 vaccine projects planned or in progress; how vaccine development – done properly – will take over eight more months

glossary
rotavirus – common RNA virus responsible for diarrhea in young children and infants. Worldwide, the virus is responsible for as many as 400,000 deaths annually. A vaccine was introduced in 2006.
protein subunit-based – Some large proteins are actually complexes of individual proteins or “subunits.” Inactivation of an essential subunit (for example, by a vaccine) inactivates the whole protein complex.
Phase III clinical trial – Clinical development of a vaccine is a three-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. (from the CDC)

Segments 2 and 3
Minutes 17:20-19:05 and 22:25-24:00
Possible importance of T cells in the immune response; the role of antibodies may not be as important as first thought; implications

glossary
antibody – part of the adaptive immune response (see “innate immunity” below), which eventually selects for proteins (antibodies) that specifically bind to foreign (usually) substances (like viral proteins). Binding of an antibody to a substance can cause inactivation of that substance.
serology – the analysis of blood for the presence of antibodies that bind specific substances (in this case, to proteins of COVID-19). A positive serology test for COVID-19 means that you are now infected or have been infected sometime in the past.
T and B cells – The white blood cells are important to the immune response. Several types of white blood cells have been identified. T cells and B cells are two major classes. B cells produce antibodies. Two subtypes of T cells are known to be important for the immune response to COVID-19. One subtype signals B cells to produce antibodies. Another subtype (cytotoxic T cells) kill virus-infected cells. The scientists discuss the evidence that the latter subtype of T cells may be very important to the immune response to COVID-19.
innate immunity – the first line of defense or the non-specific arm of the immune response. The innate immune response is in contrast to the adaptive (specific) immune response, which includes antibody production and takes days to develop.
PI – Principle Investigator; the head of the project
neutralizing antibody – an antibody that blocks infection by the virus; for COVID-19, an antibody that inactivates the spike protein of the virus (see below) is a neutralizing antibody
IgG – Immunoglobulin Gamma; the majority of the long-lived antibodies in the blood
immunopathology – that part of a disease that is caused by the immune response

Segment 4
Minutes 26:25-29:40
Which vaccine will be the best? What should we think of a vaccine based on spike protein only?

glossary
MHC – Major Histocompatibility Complex – several genes that code for a large set of proteins that are on the surface of every cell. T cells monitor what the MHC surface proteins are bound to. Fragments of proteins (see “peptide” below) are bound to MHC proteins and displayed to a T cell by cell-cell contact. If a cytotoxic T cell recognizes the fragment as normal or “self,” it takes no action. If the cytotoxic T cell “sees” a peptide as different or foreign (as in a virus-infected cell), it will kill the cell. This is part of the innate immunity arm. Stimulation of a T helper cell by an MHC protein bound to a foreign peptide will signal the adaptive arm of the immune response, which includes antibody production.
peptide – a small fragment of a protein
antigen – a substance that stimulates the production of antibodies to itself and molecules very similar to itself. COVID-19 vaccine production uses one or more viral antigens to trigger an immune response in the absence of infection by the virus.
spike protein – a protein of COVID-19; important because it’s needed for the virus to bind tightly to the ACE2 (angiotensin converting enzyme 2) protein that’s on the surface of lung cells; the binding is needed for the virus to gain entry to the cell and start the infection; a target for some vaccines; antibodies that inactivate spike are called “neutralizing antibodies.”
attenuated – An inactivated virus is a virus that’s been killed. An attenuated virus is a live virus that replicates and induces the immune response the natural way, but no longer causes disease. The Salk polio vaccine is based on killed virus. The Sabin vaccine is based on an attenuated polio virus. (Interesting note: Vincent Racaniello sequenced the chromosomes of the normal and Sabin polio viruses and identified three mutations in the Sabin virus.)
Zika virus – a mosquito-borne virus that was first identified in Uganda in 1947 in monkeys. It was later identified in humans. In most cases, there are no symptoms. Most frighteningly, in pregnant women, it may cause subsequent birth defects, including microcephaly (small head due to an undeveloped brain). In early 2015, a widespread epidemic, caused by the Zika virus in Brazil, spread to other parts of South and North America. There’s no vaccine or specific treatment. (from WHO and Wikipedia)

Segments 5, 6, and 7
Minutes 29:55-36:45, 40:45-41:30, and 43:00-43:30
A paper by scientists in Italy provides data from a large pool of people to show that it’s easy to become infected by contact with an infected person, even though the infected person may have no symptoms, and also to show that the greater a person’s age is, the higher is the likelihood of having COVID-19 symptoms. (Seventy-four percent of people under 60 were asymptomatic!)

glossary
PCR-positive – The test for infection is the rapid and convenient PCR (polymerase chain reaction) test. It detects the RNA chromosome of the virus. A PCR-positive result is taken as evidence that the person tested currently has an infection. (But, the test is so sensitive that it can sometimes detect fragments of viral RNA in a recovered patient.)
sero-positive – A positive result in a serology test of a blood sample indicates the presence of antibodies to proteins of COVID-19. The virus does not need to be present for a person to be sero-positive. Such a result indicates that the person is currently infected or was infected in the past.

 

Stay Safe and Healthy!

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(Photos compliments of contributor.)

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COVID-19 — It’s Everywhere . . . Progress in Controlling COVID-19

Progress in Controlling COVID-19

by

Columbia University Professor Emeritus, Dr. David Figurski

presented by

Donna O’Donnell Figurski

 

(Disclaimer: The World Health Organization <WHO> has officially named the new coronavirus as SARS-CoV-2 and the disease it causes as COVID-19. Because the majority of people, including much of the press, commonly refer to the virus as “COVID-19,” to avoid confusion I use COVID-19 as the name of the virus in these posts.)

COVID-19

David H. Figurski, Ph.D & Survivor of Brain Injury

 

 

I want to tell you about an amazing podcast, TWiV (This Week in Virology), created and hosted by Dr. Vincent Racaniello, a colleague of mine at Columbia University.

Vincent’s a virologist who has done cutting edge research on the molecular biology of influenza virus, poliovirus, and rhinoviruses (which cause the common cold). His podcasts feature several PhDs in microbiology (virologists, an immunologist, a parasitologist, and a science reporter who earned his PhD with Vincent) discussing the latest research and advances in viruses.

Vincent has been self-quarantining at home. Consequently, since March 13th, he has made more than 30 podcasts, nearly all concerning COVID-19, potential therapies and vaccines, and pandemics. His guests have been infectious disease scientists doing research or physicians in the trenches learning about the clinical manifestations of the virus and how to treat their patients.

Dr. Vincent Racaniello – Columbia University Virologist

Vincent’s podcasts are made for non-scientists to understand, but they are 1-2 hours long. Probably none of you has the time to listen that long. Therefore, I’m trying to listen to them so I can point you to episodes and minutes you may want to hear.

Podcast #622, released June 2, featured Dr. Emmie de Wit of the Rocky Mountain Labs in Montana. She’s a virologist doing drug and vaccine research in monkeys. Because Rocky Mountain Labs is one of the few places in the country with a high-safety-level facility, Dr. de Wit has worked with several dangerous viruses: SARS-1, MERS, pandemic influenza strains, and Ebola. Now she’s working with SARS-2.

I’ve boiled down Episode #622 to four segments totaling ~16 minutes.

  1. 26:05-26:35 – The spike protein of the virus coat initiates infection of a cell by attaching to the ACE2 protein (angiotensin converting enzyme 2) on the cell’s surface. Here Emmie tells how it took only days to identify ACE2 and confirm viral binding. Rich Condit, a virologist, was astonished by the speed. ACE2-binding by spike is a potential drug target.

 

  1. 37:15-39:44 – The PCR test (polymerase chain reaction), simple enough to be done on a large scale, detects the 30,000-nucleotide (or base) RNA chromosome of the virus. But, PCR is so sensitive that it can detect degradation fragments of the RNA, even though the person is no longer contagious. The only way to tell for sure is to detect viable virus in cell culture. This is hard to do and is only done in virology research labs. As a result, a person is considered infected and contagious if the PCR test is positive.

  1. 43:35-54:05 Remdesivir, an antiviral drug, is a nucleotide-analog that blocks the copying of the RNA chromosome to make more virus. Emmie showed that giving remdesivir to monkeys early (at 12-hours post infection) was very effective. But, humans don’t show symptoms for days, and, because remdesivir must be administered intravenously, patients are only given remdesivir if they are hospitalized. This is very late, and still there is a modest effect. Rich Condit talks about the possibility of producing an oral form of the drug. Then remdesivir could be taken earlier – maybe even at home – and might be very effective in humans.

 

  1. 58:25-60:40 This segment concerns a vaccine. (I’ll write more on this topic later, but you should know that there are three types of promising technologies: the viral protein-based, the viral gene-based, and the virus vector-based, in which a harmless virus carries a gene from a disease-producing virus for a protein that’s needed to infect cells.)2ff087415a5009984739aa8fde5d5d4a

Emmie tested a harmless chimpanzee adenovirus that was engineered to carry the COVID-19 spike gene. This adenovirus produces the coronavirus spike protein, needed for COVID-19 to infect cells. So, this harmless adenovirus should cause us to make antibodies that will block infection by COVID-19.

In Emmie’s experiment in monkeys, the vaccine worked so well that it allowed clinical trials to proceed in humans.

Stay Safe and Healthy!

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(Photos compliments of contributor.)

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