FOR THE RECORD: I am not "anti-vaccine" per se or as a "general rule" with all vaccines... but... I do think that if we are to be 100% consistent with regards to respecting "science" and it's (so-called) authorities, we should also be wise to consider carefully the following scientific facts as well and be sure to take an appropriate dose of healthy skepticism with how breathtakingly fast this is all happening and we are expected to fully trust and submit those behind it...
What History Tells Us About Vaccine Timetables
The time needed for the technical development of a vaccine is almost invariably and grossly underestimated
Jens-Peter Gregersen, DVM | EUREKA
When will there be a coronavirus vaccine?
More than 30 years ago, I was asked the same question about an AIDS vaccine. Being a realistic optimist, my answer was: I do not expect a vaccine earlier than five years from now. None of the many journalists who asked me that question ever quoted those five years. Far too pessimistic! Other scientists spoke about one or two years. They were cited in the newspapers (and I was no longer harassed by journalists).
Three decades later, we are still waiting for an AIDS vaccine effective enough to be licensed.
I learned a valuable lesson then. Today, when I get asked the same question about the novel coronavirus, I respond by repeating the question with a different emphasis: “When do WE (all) get the coronavirus vaccine?” And there are other important questions to be added: Will it be safe? Will it be reliably protective?”
An average vaccine takes about 10-12 years to be developed.
This does not include those vaccine projects that did not make it to market but it does include a number of “me too” vaccines (vaccines undifferentiated from those already on market.) Those me-too vaccines are clearly the majority among past vaccine development projects and greatly influence the average time needed.
The figure below provides an overview on normal vaccine development, its phases and its average duration.
For comparison here is how coronavirus vaccine development is being explained to the general public:
“Make some milligrams of the desired antigen. Can be done in few weeks or months. Or, if you aim at a DNA or RNA vaccine, it may even be synthesized within days. Immunize mice with it and test the serum for antiviral antibodies. If the serum contains virus-neutralizing antibodies, you have your vaccine.”
Is this really a vaccine? No, it is only a potential vaccine candidate—one of about 100 candidates with a <5% chance to make it to the market.
“Make some milligrams of the desired antigen. Can be done in few weeks or months. Or, if you aim at a DNA or RNA vaccine, it may even be synthesized within days. Immunize mice with it and test the serum for antiviral antibodies. If the serum contains virus-neutralizing antibodies, you have your vaccine.”
Is this really a vaccine? No, it is only a potential vaccine candidate—one of about 100 candidates with a <5% chance to make it to the market.
The questions we ought to be asking are: Is there a process to manufacture this “vaccine” at large scale? Can it be made reproducibly at the same quality—and of what quality? How can we purify it to a degree that unwanted components are avoided? Which methods are required to analyze raw materials, intermediates and the final vaccine? How much investment is needed to set up the required facilities and to qualify these for GMP (Good Manufacturing Practice)? Or do we find an experienced contract development organization?
Complex questions from a different world—totally different from an academic research environment. No wonder that the time needed for the technical development of a vaccine is almost invariably and grossly underestimated. In practice, the technical development phase is not even a defined phase with an average duration; it marks the start of development and does not end until a vaccine is licensed. It continues throughout the entire clinical phase and often beyond.
Complex questions from a different world—totally different from an academic research environment. No wonder that the time needed for the technical development of a vaccine is almost invariably and grossly underestimated. In practice, the technical development phase is not even a defined phase with an average duration; it marks the start of development and does not end until a vaccine is licensed. It continues throughout the entire clinical phase and often beyond.
In an urgent situation one might choose the fastest way forward: Take established technologies and methods, make about 1000 doses of the vaccine and then check if it is safe in laboratory animals and stable with regard to essential characteristics.
If so, apply for a Phase I clinical study, recruit a few volunteers and test different doses to see if this vaccine can be applied without causing undesired or unexpected side reactions. All this can be accomplished in a rather short period of time and the chances of success until this phase are quite reasonable. But we are still far away from a real vaccine!
On average, and including the high number of “me-too” vaccine projects, about 50% of the vaccine candidates pass Phase I successfully. Phase II clinical trials are much more demanding but still ~ 30% of vaccine projects survive this phase. However, the majority of vaccine development projects end here.
If so, apply for a Phase I clinical study, recruit a few volunteers and test different doses to see if this vaccine can be applied without causing undesired or unexpected side reactions. All this can be accomplished in a rather short period of time and the chances of success until this phase are quite reasonable. But we are still far away from a real vaccine!
On average, and including the high number of “me-too” vaccine projects, about 50% of the vaccine candidates pass Phase I successfully. Phase II clinical trials are much more demanding but still ~ 30% of vaccine projects survive this phase. However, the majority of vaccine development projects end here.
For new indication vaccine candidates, less than 5% will proceed to Phase III clinical trials. These are the ones with promising clinical data, competitive technologies and reasonable cost of goods—relevant factors to justify the high expenses expected for the clinical Phase III. A vaccine for Phase III studies must be identical to the desired end product. If not, the ultimate Phase III clinical proof-of-safety and efficacy under practical conditions will have been in vain because the tested vaccine is not the same as the final one.
For a coronavirus vaccine we need millions of doses. To do this you most likely need a dedicated facility: a new building, new equipment, facility qualification, process validation, trained operators which might take several years. Let us hope for a technology that fits well into an existing vaccine plant which is not needed for other life-saving vaccines.
So make your own estimates on how long it might take until there is a coronavirus vaccine for millions who want it. Be optimistic! Assume that every technical work is successful right away. Assume that the required manufacturing technology is already established and can be applied and scaled up as required. Assume that the antigen candidate does induce protective responses and no unexpected adverse effects. Assume that unlimited resources and money is provided. You may also correctly assume that licensing authorities will be very pragmatic and treat a coronavirus vaccine with absolute priority.
However, please do not assume that the vaccine will be accepted, if one cannot prove that it is safe, effective, and of reproducible quality.
In other words, any substance, which when injected into research models, produces a scientific paper (or a news story in the press) is NOT yet a vaccine!
In other words, any substance, which when injected into research models, produces a scientific paper (or a news story in the press) is NOT yet a vaccine!
READ MORE:
Could mRNA COVID-19 vaccines be dangerous in the long-term?
MAAYAN JAFFE-HOFFMAN | THE JERUSALEM POST
‘There is a race to get the public vaccinated, so we are willing to take more risk.'
The Israeli-born chief medical officer of Moderna, Inc. told The Jerusalem Post on Monday that he is feeling “awesome,” after his company reported its experimental vaccine was 94.5% effective in preventing COVID-19, based on interim data from a late-stage clinical trial.
“It’s a wonderful day. Beautiful data,” CMO Tal Zaks said.
Moderna, a relatively young American start-up, was the first company to enter clinical trials. Its announcement comes just one week after another American company. Pfizer Inc., released data that showed its similar mRNA vaccine to be more than 90% effective.
Pending more safety data and regulatory review, the United States could have two vaccines authorized for emergency use in December, with as many as 60 million doses of vaccine available by the year’s end. Next year, the US government could have access to more than a billion doses just from the two vaccine makers, more than needed for the country’s 330 million residents.
THE DATA from Moderna’s 30,000 participant-strong trial also showed that the vaccine prevented cases of severe COVID-19, a question that still remains with the Pfizer vaccine. Of the 95 cases of infections in Moderna’s trial, 11 were severe and all 11 occurred among volunteers who got the placebo.
Moderna, part of the US government’s Operation Warp Speed program, expects to produce around 20 million doses of the vaccine for the US this year, millions of which the company has already made, and is ready to ship if it receives FDA authorization.
“Assuming we get an emergency use authorization, we’ll be ready to ship through Warp Speed almost in hours,” Moderna president Stephen Hoge said. “So, it could start being distributed instantly.”
The 95 cases of COVID-19 included several key groups who are at increased risk for severe disease, including 15 cases in adults aged 65 and older and 20 in participants from racially diverse groups.
Most side effects were mild to moderate. A significant proportion of volunteers, however, experienced more severe aches and pains after taking the second dose, including about 10% who had fatigue severe enough to interfere with daily activities while another 9% had severe body aches. Most of these complaints were generally short-lived, the company said.
Moderna, part of the US government’s Operation Warp Speed program, expects to produce around 20 million doses of the vaccine for the US this year, millions of which the company has already made, and is ready to ship if it receives FDA authorization.
“Assuming we get an emergency use authorization, we’ll be ready to ship through Warp Speed almost in hours,” Moderna president Stephen Hoge said. “So, it could start being distributed instantly.”
The 95 cases of COVID-19 included several key groups who are at increased risk for severe disease, including 15 cases in adults aged 65 and older and 20 in participants from racially diverse groups.
Most side effects were mild to moderate. A significant proportion of volunteers, however, experienced more severe aches and pains after taking the second dose, including about 10% who had fatigue severe enough to interfere with daily activities while another 9% had severe body aches. Most of these complaints were generally short-lived, the company said.
Moderna’s data provide further validation of the promising but previously unproven mRNA platform, which turns the human body into a vaccine factory by coaxing cells to make certain virus proteins that the immune system sees as a threat and mounts a response against.
The company expects to have enough safety data required for US authorization in the next week or so and expects to file for emergency use authorization in the coming weeks.
Moderna has received nearly $1 billion in research and development funding from the US government and has a $1.5b. deal for 100 million doses. The US government also has an option for another 400 million doses.
The company hopes to have between 500 million and 1 billion doses in 2021, split between its US and international manufacturing sites and partially dependent on demand.
The US government has said COVID-19 vaccines will be provided free to Americans, whether they have health insurance, are uninsured or are covered by government health programs such as Medicare.
Moderna also said it will use its data to seek authorization in Europe and other regions.
...
Rivka Abulafia-Lapid, a senior virology lecturer at the Hebrew University of Jerusalem, expressed concern about the long-term effects of mRNA vaccines on the body.
“We are looking at short-term safety issues – headache, fever, vomiting – but we cannot see what happens in the future: what we will see on the cellular level in a couple of years,” she said in a previous interview. “This is not something easy to predict.”
.jpg)
%20(1).jpg)
No comments:
Post a Comment