Attenuated adaptation may decrease SARS-CoV-2 virulence.

ATTENTION WORLD SCIENTISTS!

  Can rapid viral mutations be used to the benefit of today's researchers in the development of attenuated vaccines. How quickly does the SARS-CoV-2 virus mutate?      "By serial passage of a virus through a different species, the virus becomes more adapted to that species, and less adapted to its original host, deceasing virulence with respect to the original host (e.g. it is "attenuated"). ..

Having discovered how to vaccinate against microorganisms, Rabies presented a new obstacle for Louis Pasteur in the development of a successful vaccine. Unlike chicken cholera and anthrax, both caused by bacterium, the microorganism causing the Rabies disease could not be specifically identified, meaning Pasteur would not be able to develop the vaccine in vitro (in the laboratory).

 Pasteur did not know this at the time, but the reason he could not find the microorganism is because rabies is a viral disease. Viruses are small infectious agents that replicate quickly and have a high mutation rate. These rapid mutations can be used to the benefit of researchers in the development of an attenuated vaccine. By serial passage of a virus through a different species, the virus becomes more adapted to that species, and less adapted to its original host, deceasing virulence with respect to the original host (e.g. it is “attenuated”). By passing the virus through rabbits, Pasteur made the virus less dangerous to human hosts, while still giving the body enough information to recognize the antigen and develop immunity to the “wild” version of the disease.

Louis Pasteur in his laboratory, painting by Albert Edelfeldt in 1885.

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Attention world scientists,,,can the same process of passing a SARS-COV-2 through a rabbit and allowing the virus to mutate and adapt to rabbit cells, reduce the virulence of the virus and thus make the weakened virus usable as a vaccine in humans?

 If you are using a similar method in vitro, and it works,..great! But if not Louis Pasteur may have left important information for you! 

Personally, I like what Leor Weinberger discovered in the back of his laboratory.

---

ARE YOU TOO SMART TO BE FOOLED? THINK AGAIN.

 A CONSUMER PROTECTION GUIDE ON

 SCAM PRODUCTS NOT WORTH BUYING.

DID YOU BUY A PRINTER THIS YEAR? 

1. UP UNTIL RECENTLY, ALL PRINTER COMPANIES TRIED TO SELL YOU A CHEAP PRINTER WITH THE IDEA OF SELLING VERY EXPENSIVE INK.  THE  SCAM WAS SIMPLE. SELL A CHEAP PRINTER AND MAKE THE IDIOT CONSUMER BUY EXPENSIVE INK.  THEY MADE CERTAIN THE PRINTER IN THE BOX CONTAINED ONLY A SMALL SAMPLE OF INK IN A SMALL PLASTIC CARTRIDGE AND IF YOU WANTED MORE INK, THE PRICE PER CARTRIDGE JUMPED UP...WAY UP,,, AND I WAS ONE OF THE STUPID CONSUMERS.

 CONSUMERS HAD TO CHANGE THE CARTRIDGE EVERY FEW WEEKS AND  THEN ADDING INSULT TO INJURY, THE COMPANIES CREATED INK INSURANCE PROGRAMS PROMISING NEW INK WOULD BE DELIVERED TO YOUR DOOR QUICKLY SO YOU WOULD NEVER RUN OUT OF INK...MONEY YES...INK NO. 

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2. TODAY, ALMOST EVERYBODY UNDERSTANDS HOW OIL, GAS AND CAR COMPANIES OPERATE. THEY WANT YOU TO BUY GAS MADE FROM OIL AND SO MANUFACTURING COMPANIES SPEND MILLIONS ADVERTISING GAS BURNING CARS AND TRUCKS EVERY TWO MINUTES ON TELEVISION. CARS BURN MORE GAS AS THEY GET OLDER AND SO THE USED CAR MARKET IS PROLIFERATING AND THE AFTERMARKET IS FLUSH WITH CASH. COMPANIES BENEFITTING FROM INTERNAL COMBUSTION ENGINE CARS ARE: CAR INSURANCE COMPANIES, PART SUPPLIERS, GARAGES, EVEN THE GOVERNMENT IS PROFITING WITH HIGH TAXES ON GAS. AS FOR THE ENVIRONMENT, COLD HEARTED COMPANY CEO'S CONTINUE TO DECIDE FOR ALL OF US HOW OUR PLANET WILL ABSORB THE POLLUTION THEIR MACHINES CREATE. P.S. WARNING...CLIMATE EMERGENCY!

========================================

  TODAY, I ADVISE YOU TO SEEK SHELTER FROM THE APPROACHING HURRICANES AND RUN FROM THE FOREST FIRES. AIR POLLUTION IS UNAVOIDABLE BECAUSE LARGE CAR AND TRUCK COMPANIES HAVE CROSSED THE LINE OF DECENCY WITH BRAIN WASHING ADVERTISING EVERY FEW MINUTES ON TELEVISION. I DON'T SIMPLY DISLIKE THE PEOPLE WHO ARE DOING THIS, I DESPISE THEM!

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3. FOAM BED MATTRESSES.  EVERYBODY HAS HEARD ABOUT MEMORY FOAM MATTRESSES AND HOW COMFORTABLE THEY ARE.  WHAT I DISCOVERED AFTER BUYING ONE OF THESE IS THAT NOT ALL FOAM MATTRESSES ARE MADE EQUAL. SOME ARE SOFTER, SOME ARE HARDER AND SOME MELT IN WATER. YES, THEY MELT UNDER YOU IF YOU SWEAT AND THEY CREATE HOLES SO THAT THE PROMISE OF CONFORMING TO YOUR BODY IS ACCURATE BUT AFTER A YEAR OR SO THEY DO NOT RETURN TO NORMAL. THEY REMAIN LUMPY. AS FOR THE RIDICULOUS OVER-PRICING OF THESE MATTRESSES, THEY FALL INTO THE SCAM CATEGORY AND SO IF LIKE ME YOU BOUGHT ONE OF THESE, YOU HAVE BEEN SCAMMED

 IF YOU DON'T BELIEVE ME, PUT AN OLD FOAM PILLOW IN WATER AND WATCH IT DISSOLVE.

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4. I BOUGHT AN EPSON ET-7700 INK TANK PRINTER AND I THOUGHT I HAD A GOOD DEAL. The company promised two years worth of ink. I MANAGED TO MAKE SOME EXCELLENT PHOTOGRAPHS BEFORE THE FUN STOPPED!  After a few months of usage the  photographs created by my Epson ET-7700 printer developed ink blotch problems. However, the printer is programmed to clean itself and it did that by using a small plastic cleaning box, which is sold separately. What the company did not explain is how quickly the cleaning box fills up with waste ink and how expensive the unit is to replace.. It also takes about a week for the replacement to arrive. I am waiting patiently to see if my photographs improve after I replace the box. 

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5. THIRTY YEARS AGO ALL I HAD TO DO WAS PLUG IN A PRINTER TO AN ELECTRICAL WALL OUTLET,  CONNECT THE USB CABLE TO THE PRINTER AND THEN GET TO WORK BUT THAT WAS THIRTY YEARS AGO, BEFORE  DEVIOUS CORPORATE MINDS FOUND A WI-FI WAY TO STICK IT TO CONSUMERS.

==============================================

6. Dollar store products break soon after purchase and since they are so cheap, people simply throw them into a recycle bin and hurry to buy more of the same crap. We need to bring small business back to North America run by quality artisans. Most Europeans are not fooled into buying useless garbage and their industries as well as their artisans make beautiful long lasting quality products.

===============================================

   

THEY TOLD ME I HAVE ROTTEN IDEAS!

MY POLITICAL ENEMIES...

  THEY TOLD ME TO STOP CORRUPTING THIER LIVES WITH MY ROTTEN IDEAS!!

 MY IDEAS INCLUDE:

1. Helping those less privileged than myself. The homeless need both shelters and social help.

2. Following a middle of the road path in life with a gentle caring philosophy.

3. Studying the science of Physics and the underlying principles that form our Universe.

4. Studying Botany, Biology, and Medicine while completely understanding that my Homo Sapien specie is a territorial carnivore willing to slaughter and eat domesticated species such as Cows, Chickens and Pigs. I enjoy explaining how a vegetarian diet maintains good health. 

5. Studying the territorial imperative in order to understand why many animal species, including human, fight and are willing to kill for territory.

6. My ideas include politely asking people who enjoy moving quickly from one territory into another, to stop pumping Carbon Monoxide into the air we all need to breath. Why not drive Electric cars or ride Bicycles or utilize (non-polluting) public transportation?

7. My ideas include creating or improving water filtration plants, recycling depots and planting a millionTrees and thousands of vegetable and flower gardens every single year, everywhere!

8. I suggest planting: grass, trees, flower and vegetable gardens in every school yard in Canada and assigning students to learn about and care for the plants.

9. I suggest we transform business sky scrapers into partial Hydroponic Green Houses and ask office workers to spend a few hours a day caring for plants.  Italy has a high rise apartment building covered with growing plants..

10. I suggest the race for money and power slow down to a crawl and a new race to stop pollution begin.

11. For long distance travel I propose we create Pony Express style Electric Busses that can simply be exchanged every five hundred miles. While one bus is being charged passengers can transfer and continue their journey in another fully charged bus. The same thing can be created within city limits with smaller and quicker and more manuverable busses. 

12. Electric trains already exist. The Japanese have fantastic high speed Maglev trains which North Americans should have adopted years ago. Electric cars are now on the market and momentum for these vehicles has picked up speed. We need charging stations on every telephone pole across North America to make sure nobody is forced to sit waiting in a dead-battery car. The poles could also be covered with flexible Solar panels wired to charge a large battery sitting under the pole. A CREDIT CARD CAN BE USED TO ACTIVATE A POLE CHARGING STATION IN THE SAME WAY THEY DO IN PARKING GARAGES.

13.  The same people who service and pump gas into our cars today, can continue to service cars as battery exchange specialists. We need cheaper assembly line Electric vehicles with removable battery packs.  Inexpensive cars that have quick slide-in-and out replaceable battery packs exactly like today's wonderful cordless drills.

14.  With human population density becoming a serious problem, I suggest sex education begin in early childhood and birth control positively motivated and encouraged among young adults.  

15. One final thought. I am not Jesus Christ and I do not appreciate being crucified for my ideas. 

DOES JUSTIN TRUDEAU BELIEVE IN THE MONARCHY?

 

GENTLE PEOPLE:

 IF YOUNG CANADIAN PRIME MINISTER JUSTIN TRUDEAU BELIEVES IN THE MONARCHY, HE IS CERTAINLY NOT FOLLOWING THE EXAMPLE SET BY GREAT BRITAIN.

 ENGLAND IS INVESTING ELEVEN BILLION POUNDS TOWARDS GREENING THEIR ISLAND. 

BEFORE 2030, THEY PLAN TO CREATE AN INFRASTRUCTURE OF CHARGING STATIONS FOR THE ELECTRIC CARS THEY ARE CREATING, AND WITH MORE TREE PLANTING PROJECTS, MORE WINDMILLS AND A GOAL OF ZERO FOSSIL FUEL EMISSIONS FOR THEIR MAJOR INDUSTRIES, THEY ARE SETTING A GOOD EXAMPLE FOR THE WORLD.

 IN COMPARISON WHAT IS CANADA DOING?

 CANADA JUST RE-OPENED A PICK-UP TRUCK MANUFACTURING PLANT IN OSHAWA, ONTARIO.  THE GAS BURNING 'GENERAL MOTORS' VEHICLES HAVE BEEN ADVERTISED ALL SUMMER LONG ON CANADIAN TELEVISION TO THE POINT OF SATURATION. 

  IF THOSE TRUCKS WERE ELECTRIC THESE WORDS WOULD NOT EXIST BUT ONCE AGAIN OUR P.M. IS PROVING TO BE A PRO OIL AND GAS WONDER BOY! I WONDER HOW HE CAN CLAIM TO THE WORLD HE IS PRO ENVIRONMENT WHEN HE CONTINUES TO ALLOW THE PROLIFERATION OF OIL PIPELINES AND GAS BURNING CARS AND TRUCKS IN CANADA? THE CITIZENS OF OSHAWA, ONTARIO, NEED A LONG RANGE GREEN ECONOMIC PLAN AND FOSSIL FUEL BURNING TRUCKS IS NOT THAT PLAN!

  I WONDER HOW LONG P.M TRUDEAU WILL REMAIN IN POWER IF THE N.D.P. AND THE GREEN PARTY PULL THE RUG OUT FROM UNDER HIM...GEE! I WONDER?   J.N.R.

 

wow! what I have learned so far is great!

WHAT I HAVE LEARNED SO FAR!

 GENTLE PEOPLE:

   LIKE THOUSANDS OF JOURNALISTS AROUND THE WORLD, I HAVE BEEN FOLLOWING THE PROGRESS OF VACCINE RESEARCH IN THE MOST HIGHLY SUBSIDIZED LABORATORIES AROUND THE WORLD...ONLY TO BE DISAPPOINTED WITH THE SLOW AND OFTEN NEGATIVE RESULTS PRODUCED BY THOSE SAME LABORATORIES. THIS WEEK, THANKS TO PROFESSOR LEOR WEINBERGER, THERE IS NEW HOPE ON THE HORIZON! I NOW UNDERSTAND WHY PROGRESS HAS BEEN SO SLOW AND IT IS NOT THE FAULT OF THE LABORATORIES BUT THE NATURE AND ABILITY OF VIRUSES TO MUTATE, SURVIVE AND INFECT. 

 THE SARS-COV-2 OR COVID-19 VIRUS ENTERS A HUMAN CELL AND HIJACKS THE REPLICATION MACHINERY OF THE CELL, SILENTLY REPLICATING ITSELF AND INFECTING MORE HUMAN CELLS AND THEN PROVOKING A DANGEROUS IMMUNE RESPONSE...

  NOW, HOWEVER,  IT WILL BE POSSIBLE, USING CAS 9 AND CRISPR, TO REPROGRAM AND CREATE GOOD VIRUSES THAT WILL DO THE EXACT SAME THING TO NASTY VIRUSES WITHOUT PROVOKING AN IMMUNE RESPONSE THAT KILLS BOTH THE VIRUS AND THE HUMAN CELL. 

 WHAT I HAVE LEARNED RECENTLY IS THAT DANGEROUS VIRUSES: REPLICATE, MUTATE AND TRANSMIT AND UP UNTIL RECENTLY, THE HEAVILY SUBSIDIZED VACCINES CREATED TO COMBAT HIV, FLU, AND SARS-COV2,  DO NOT REPLICATE, MUTATE AND TRANSMIT TO COMBAT THE KILLER VIRUS. AFTER TWENTY YEARS OF ALMOST BURN OUT EFFORT, PROFESSOR LEOR WEINBERGER AND HIS TEAM AT THE GLADSTONE INSTITUE IN CALIFORNIA, HAVE DISCOVERED A METHOD TO CREATE AN ANTI-VIRUS VIRUS. A VIRUS SAFE FOR HUMANS BUT WHICH CAN REPLICATE, MUTATE, AND HIJACK THE DANGEROUS VIRUS AND THEN TRANSMIT ITSELF IN PLACE OF THE KILLER VIRUS, RENDERING THE KILLER VIRUS HARMLESS. THE POTENTIALLY EXCELLENT GOOD NEWS GOING ALONG WITH THIS DISCOVERY IS HOW THIS NEW FORM OF SELF-TRANSMITTING VACCINE CAN BE USED FOR ALL THE DANGEROUS VIRUSES AND NOT ONLY FOR THOSE MENTIONED ABOVE. THE CATCH 22 IS AS USUAL THE NECESSITY TO MAKE ABSOLUTELY SURE THIS NEW METHOD IS SAFE FOR USE. THE POSSIBILITY TO ERADICATE VIRAL CREATED DISEASES AROUND THE WORLD IS CLOSE...VERY VERY CLOSE!

"Viruses mutate and spread from person to person, a dynamic process that often leaves us playing catch-up when there's a new disease outbreak. What if vaccines worked the same way? Virologist Leor Weinberger shares a scientific breakthrough: "hijacker therapy," a type of medical treatment that could attack, modify and spread alongside a virus, potentially treating afflicted individuals and slowing the spread of infections like HIV."

• Leor Weinberger and his team have developed novel therapies with profound implications in depriving infectious diseases, in particular HIV, of the ability to replicate.

  

  This video was produced by TEDMED. TED's editors featured it among our daily selections on the home page.

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Gladstone Institutes is an independent, non-profit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer's disease. Wikipedia

Located in: UCSF Medical Center at Mission Bay

Address: 1650 Owens St, San Francisco, CA 94158, United States

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Closed ⋅ Opens 8:30 a.m. Mon.

President: Deepak Srivastava

Founded: 1979

Phone: +1 415-734-2000

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THE 2020 PRESIDENTIAL ELECTION.

   

   An open letter to the American people:

   From my vantage point here in Canada,  I  received the impression your president Trump had trouble reading the script created for him by his lawyer and adviser, Rudolf Gulliani. The script read like it was prepared far in advance of the election and poor Trump stumbled over a few words! 

  After listening to Trump read a litany of accusations towards the Democrats, the words sore loser and sour grapes came to mind but sticking to the facts, Trump has lost this election and will now face the U.S. tax department for having never declared his income. Some of you may remember that Donald Trump was and may still be a multi-millionaire. Nobody knows for sure because he never disclosed his income before or after he became president and he continues to live so far above the average person, he might as well be an astronaut. 

 He may prove lucky to have stuffed the U.S. Supreme Court with Republican judges as they may or may not bale him out of his financial problems if he still has any remaining financial problems, but if not, he can always escape to live with his friend in Russia. 

J.N.R.

Leor Weinberger's Anti-Virus virus...works!

• Leor Weinberger and his team have developed novel therapies with profound implications in depriving infectious diseases, in particular HIV, of the ability to replicate.

  Why you should listen

  Leor Weinberger is the Bowes distinguished professor at the Gladstone Institutes and the University of California, San Francisco, where he leads a virology discovery group focused on engineering new, resistance-proof antiviral medicines for the developing world. In 2019, Weinberger and his group succeeded in developing the first Therapeutic Interfering Particles (TIPs) and showed it to be effective against HIV in animals. He holds numerous patents for inventing novel antiviral medicines.

  Weinberger served on the Bill & Melinda Gates Foundation Innovation review panel, and his research has been widely published in Science, Nature and Cell. He was a Pew Scholar, a Keck awardee, and a Sloan Fellow. He is the only person to win the NIH Director's Pioneer, Avant Garde and New Innovator Awards.

  Leor Weinberger’s TED talk

  20:59

  Leor Weinberger

  Can we create vaccines that mutate and spread?

  Posted Oct 2020TED Speaker

https://www.ted.com/speakers/leor_weinberger? 

Viruses mutate and spread from person to person, a dynamic process that often leaves us playing catch-up when there's a new disease outbreak. What if vaccines worked the same way? Virologist Leor Weinberger shares a scientific breakthrough: "hijacker therapy," a type of medical treatment that could attack, modify and spread alongside a virus, potentially treating afflicted individuals and slowing the spread of infections like HIV.

This video was produced by TEDMED. TED's editors featured it among our daily selections on the home page.

ABOUT THE SPEAKER

Leor Weinberger · Virologist

Leor Weinberger and his team have developed novel therapies with profound implications in depriving infectious diseases, in particular HIV, of the ability to replicate.

Virologist

 Weinberger Lab

Viruses mutate and spread from person to person, a dynamic process that often leaves us playing catch-up when there's a new disease outbreak. What if vaccines worked the same way? Virologist Leor Weinberger shares a scientific breakthrough: "hijacker therapy," a type of medical treatment that could attack, modify and spread alongside a virus, potentially treating afflicted individuals and slowing the spread of infections like HIV.

This video was produced by TEDMED. TED's editors featured it among our daily selections on the home page.

ABOUT THE SPEAKER

Leor Weinberger · Virologist

Leor Weinberger and his team have developed novel therapies with profound implications in depriving infectious diseases, in particular HIV, of the ability to replicate.

Celebrate Life!

 From human4us to human4us2

• Hello from Canada! Life is the opposite of deat...

• October 2006

TUESDAY, OCTOBER 10, 2006

Hello from Canada!

Life is the opposite of death. Today and tomorrow, death will be in the headlines and life will once again take a back seat. This blog intends to celebrate life to the fullest extent possible and I invite you to celebrate with me! As we celebrate, I am certain a few currently profiting from death will pause to wonder and maybe they also will decide to celebrate life.
In order to celebrate life we Human Beings must first understand life. To understand is to think and I believe there are enough thoughtful people in the world to create a new level of Human self awareness. If you are not conscious you are either asleep or in a coma or dead. Most living creatures think and after they have eaten and slept and gone to the bathroom, many species like to play and also to enjoy the world around them. In order for millions of my fellow Homo Sapiens to celebrate life, I have to make sure they have eaten and slept and gone to the bathroom. 
Finding food for millions of hungry Humans is difficult but not impossible. I invite your ideas and suggestions on how to feed millions of poor people in Africa and around the world in order that they also may celebrate life! 
While you are at it, try helping that poor homeless person sleeping in the alley behind your building. We have a lot of celebrating to do and we have to get busy thinking!

A great little video explaining vaccines today.

Look up this great little video...https://edhub.ama-assn.org/jn-learning/video-player/18547208   

(Transcript)

Researchers are racing towards the goal of delivering a safe and effective vaccine that could curb the COVID-19 pandemic. And production scale-up for some of the vaccine candidates has already started. Consider the US government's Operation Warp Speed:

[Robert Redfield, MD:] You know I spent time in the military, so I like that concept of focusing on a mission. And the mission is to have a vaccine available to the American public by January 2021. We're on an accelerated course here that I've not witnessed before.

One of the reasons why this vaccine search is breaking records is because most of the frontrunners--and nearly all the vaccines in the Warp Speed portfolio--are based on next-generation technologies that can be developed and scaled up more quickly than conventional vaccines. These new technologies are genetic vaccines and viral vector vaccines.

These technologies--also called platforms--have been in development for decades. A lot of the investment in them has specifically focused on their potential to combat emerging infectious diseases. And COVID-19 is putting that potential to the test. Let's take a look at how they work, and how they're different from conventional vaccines.

In these pictures from 1953, (locate the video above) the scientists are developing an influenza vaccine. They're injecting viruses into fertilized eggs, which are then incubated to allow the virus to replicate within the eggs. Growing the virus is necessary for developing live attenuated virus and whole inactivated virus vaccines--these are the two classic approaches where the virus is either weakened or killed. These approaches are still in use today, although different cell cultures are most often used instead of eggs.

But since those photos were taken, huge advancements in the field of vaccinology have introduced multiple other approaches to developing vaccines. Here are the major types of vaccines being deployed against COVID-19. Unlike the two classic vaccines, these four types, which include the next-generation platforms as well as more conventional approaches, don't require researchers to handle any of the actual virus.

[Anthony S. Fauci, MD:] The Chinese, when they made the diagnosis and showed it was a coronavirus, they put the sequence up on a public database. So today you don't need the virus in hand. All you need is a sequence.

This is that published sequence for SARS-CoV-2. Because of previous research into SARS-1 and MERS, researchers knew that they could focus initial attention on the S protein, also known as the spike.

The spike is the protein that studs the surface of the SARS-CoV-2 virus. It's also necessary for viral entry into human cells. So a vaccine that exposes the immune system to just the spike should induce a protective immune response. And that's the strategy behind the majority of COVID-19 vaccine candidates, which use both next-generation and more conventional approaches. The scientific way to put this is that the spike is the target antigen in these vaccines.

Where the next-generation vaccine platforms differ from those more conventional vaccines is how the immune system is exposed to the spike, or the antigen. Conventional vaccines contain the antigen itself. Now compare this to genetic vaccines:

[Paul A. Offit, MD:] You can take just really to the genetic material, either as messenger RNA or DNA, that then codes for that spike protein. So the person makes the protein. You're not giving them the protein. You're giving them the genetic material that then instructs them how to make that spike protein, to which they make an antibody response that hopefully is protective.

Two types of genetic vaccines are being investigated for COVID-19: mRNA and DNA. mRNA needs to reach the cytoplasm of host cells, while DNA needs to enter the nucleus. Then this genetic material gets taken up by the cell's machinery, and the cell expresses the spike protein. These spike proteins are then recognized by the immune system, hopefully stimulating a protective response.

These two candidates in the Warp Speed portfolio are mRNA vaccines. This one was developed by Moderna and the NIH, and was the first candidate to enter clinical trials in the US, with this one from Pfizer and BioNTech following not long after. Naked mRNA cannot easily cross cell membranes passively, and it's very susceptible to degradation. So in both of those vaccines, the mRNA coding for the spike is encased in small carrier molecules called lipid nanoparticles. Both of these candidates are currently in Phase 3 trials.

Now let's look at viral vector vaccines.

The basic idea is that you take another virus and replace its genetic payload with the sequence coding for the antigen, in this case the spike protein. The goal is to induce immunity against the target antigen--the added genetic cargo. But these vaccines may also induce immunity to the vector itself. The viruses used as vectors are attenuated, or weakened, so they cannot cause disease. A lot of different viruses have been developed as vectors, and they can be broadly categorized into two buckets: replication-defective and replication-competent.

Let's start with replication-defective vectors. A very popular choice among the potential COVID-19 vaccines is adenoviruses, like these two candidates, which are both in phase 3 clinical trials. Adenoviruses are common pathogens that typically cause mild cold or flu-like symptoms. This candidate, which was developed by the University of Oxford and AstraZeneca, uses a chimpanzee adenovirus 5, while this candidate from Johnson & Johnson, uses a human adenovirus 26. In both vaccines the adenovirus vector carries the DNA coding for the spike to the host cells, but it doesn't display it on its surface. Once the virus infects a host cell, it delivers the DNA to the nucleus; the cell's machinery then expresses the spike using this DNA, similarly to what we saw with genetic vaccines. And because these adenovirus vectors are replication-defective, after the virus infects a cell, no more viruses are produced.

Now let's take a look at replication-competent virus vectors. This Warp Speed vaccine that's being developed by Merck in partnership with IAVI is an example; it uses recombinant vesicular stomatitis virus. In humans, wild-type VSV is usually asymptomatic or causes a mild flu-like illness. The researchers replaced part of its RNA sequence with RNA coding for the spike. Unlike the adenoviruses, this rVSV vector does display the spike on its surface. After the rVSV infects a host cell, again the cell's machinery expresses the spike; but because rVSV is replication competent, this platform mimics a real viral attack more closely.

This is the same platform that Merck used to develop a vaccine for Ebola, which was approved by the FDA last year. But so far that Ebola vaccine is the only viral vector vaccine that has gotten FDA approval. Adenovirus vectors, which are much further ahead in COVID-19 trials, have never been used in an FDA-approved vaccine, and there are likewise no FDA-approved vaccines that use DNA or mRNA platforms.

So despite the investment in these approaches, and the media attention they've been getting, it's far from certain they will curb COVID-19.

[Paul A. Offit, MD:] I think the reason that you hear the most about the mRNA vaccine or the DNA vaccine or these replication-defective adenovirus vaccines is because they're the easiest to make. So I think that's why you hear about them first, but I just would want to warn people that, you know, what you want is you want the best and safest vaccine, which may not necessarily be the first vaccines.

And the only way to find out is through rigorous trials. Before COVID-19 hit, these platforms were extensively studied in animal models, and some candidates were tested in phase 1 and 2 trials, but until now phase 3 data has been lacking.

[Paul A. Offit, MD:] This is the -- if the proof is in the pudding, the pudding is a phase three trial, a large, prospective, placebo-controlled, safety and efficacy trial.

And platforms do not save time in clinical trials. No matter the approach, rigorous safety and efficacy testing is required. The safety standard for vaccines is very high compared to other interventions, because vaccines are potentially given to millions of healthy people.

If the phase 3 trials are done correctly, there will be enough data about both safety and efficacy in diverse demographic groups to allow health officials, doctors and individuals to make informed decisions. Until that data has been adequately analyzed, it's too early to say which approaches, either novel or conventional, are the safest and most effective.

A handful of vaccines are already in phase 3 trials, so some data will be available soon; and at that point--not before--we might find out if these next-generation platforms have lived up to their potential for combating emerging infectious diseases.