The Anatomy of a Vaccine: The Path To Recovery?

[therock]

Covid has been with us for a while now and there are no signs that it will go away in the next few months. 
Social distancing, good hygiene, isolation and quarantine techniques have been instrumental in the initial battle and remain the primary weapons of choice in any outbreak.

But now, we are seeing more countries resort to making vaccines in the hope that it can bring about stability and a return to normalcy. 

Having spent time in the trenches against this beast, I would like to share some info on the battle against it.

R&D is now where the battle is being fought, and hopefully won..

 

However I must stress that a vaccine is no magic bullet, and all the above measures still apply and are very crucial regardless of the success of any vaccine. 

Second, the runway to creating a successful vaccine takes a lot of time - typically years and even with the accelerated development we are seeing now, it will probably be next year before we see any solid data and results.

Third, not all vaccines are the same and the success may vary.

 

With that, I'll just share some basic info on what a vaccine is, and then some info on what is the kind of R&D that goes into it and perhaps share info and get others to contribute on this matter, so we get real facts. 

 

I would like to emphasis once more that a vaccine is no magic bullet and the outlook for the rest of this year remains rather bleak... 

 

So What Is A Vaccine:

 

I think the explanation on Wiki is the best answer that balances between too simple and too technical an answer:

https://en.wikipedia.org/wiki/Vaccine

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A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognise the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.

 

[therock]

Types of Vaccines:

 

There are 4 main types of vaccines:

Live-attenuated vaccines.

Inactivated vaccines.

Subunit, recombinant, polysaccharide, and conjugate vaccines.

Toxoid vaccines.

https://www.vaccines.gov/basics/types

 

 

There are many types and all of them aim to stimulate a person's defences, which is different from say antibiotics which kill bacteria, or anti virals, which can kill viruses. Currently, there are no definitive anti-virals which work 100%.

However there are some anti-virals which show some promise. 

 

 

Edited August 16, 2020 by therock

[therock]

The current battle:

This articles summarises it well:

https://www.nature.com/articles/d41573-020-00073-5

 

[Zxcvb]

Nobody here works in Biopolis? Anyone work in the pharmaceutical industry care to input?

[therock]

How are vaccines created:

https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/

This article tracks the current production timelines:

https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

 

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Researchers around the world are developing more than 165 vaccines against the coronavirus, and 31 vaccines are in human trials. Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and effective vaccine by next year.

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PRECLINICAL TESTING: Scientists give the vaccine to animals such as mice or monkeys to see if it produces an immune response.

PHASE 1 SAFETY TRIALS: Scientists give the vaccine to a small number of people to test safety and dosage as well as to confirm that it stimulates the immune system.

PHASE 2 EXPANDED TRIALS: Scientists give the vaccine to hundreds of people split into groups, such as children and the elderly, to see if the vaccine acts differently in them. These trials further test the vaccine’s safety and ability to stimulate the immune system.

PHASE 3 EFFICACY TRIALS: Scientists give the vaccine to thousands of people and wait to see how many become infected, compared with volunteers who received a placebo. These trials can determine if the vaccine protects against the coronavirus. In June, the F.D.A. said that a coronavirus vaccine would have to protect at least 50% of vaccinated people to be considered effective. In addition, Phase 3 trials are large enough to reveal evidence of relatively rare side effects that might be missed in earlier studies.

APPROVED: Regulators in each country review the trial results and decide whether to approve the vaccine or not. During a pandemic, a vaccine may receive emergency use authorization before getting formal approval. Once a vaccine is licensed, researchers continue to monitor people who receive it to make sure it’s safe and effective.

COMBINED PHASES: Another way to accelerate vaccine development is to combine phases. Some coronavirus vaccines are now in Phase 1/2 trials, for example, in which they are tested for the first time on hundreds of people. (Note that our tracker would count a combined Phase 1/2 trial as both Phase 1 and Phase 2.)

 

Edited August 16, 2020 by therock

[therock]

2 minutes ago, Zxcvb said:

Nobody here works in Biopolis? Anyone work in the pharmaceutical industry care to input?

This effort is going on well

 

[therock]

Who's showing promise right now

(subject to change)

https://www.forbes.com/sites/kenrapoza/2020/07/21/china-coronavirus-vaccine-by-cansino-seems-to-be-working/#64067ecc5161 

 

[inlinesix]

Currently, there are 168 vaccines under development.  

https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

There are 7 vaccine under Phase III human trial:

1. University of Oxford/AstraZeneca

2. Sinovac

3. Wuhan Institute of Biological Products/Sinopharm

4. Beijing Institute of Biological Products/Sinopharm

5. BioNTech/Fosun Pharma/Pfizer

6. Moderna/NIAID

7. CanSino Biological Inc./Beijing Institute of Biotechnology

 

[therock]

[Playtime]

Ok....

Which company share to hoot???

[inlinesix]

Just now, Playtime said:

Ok....

Which company share to hoot???

None.

All vaccine producers are overpriced now.

[Playtime]

Typo

Edited August 17, 2020 by Playtime

[therock]

The time is past to invest in cheap stocks now..

and you will need to gamble on which one goes first 

once the governments insist on lower costs we will also see much lower P&L..

[therock]

https://www.straitstimes.com/opinion/an-amazing-race-to-develop-a-covid-19-vaccine

 

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WHY DOES IT TAKE SO LONG?

Dian Rahma Bakti

The Jakarta Post, Indonesia

President Joko "Jokowi" Widodo recently urged the Padjadjaran University research team to expedite the trial phase for a potential Covid-19 vaccine to just three months, but clinical trial coordinator professor Kusnandi Rusmil said it would be impossible.

Almost all experts agree that even an 18-month target for a Covid-19 vaccine is too optimistic, so the best-case scenario could see a working vaccine in the second or third quarter of 2021. History shows it took 26 years to develop a vaccine for the human papillomavirus and 25 years to secure one for the rotavirus.

Fortunately, in the case of Covid-19, scientists already have a big head start, as they are relying on groundwork from Severe Acute Respiratory Syndrome (Sars) and Middle East Respiratory Syndrome (Mers) outbreaks in 2003 and 2012, respectively. Sars and Sars-CoV-2, the virus that causes Covid-19, are roughly 80 per cent identical. So, researchers already know a good target for a vaccine: the spike protein that sits on the surface of the virus, and especially the part that binds to human cells, enabling the virus to gain entry. The scientists are already on the fast track and they can move to focus on other crucial parts ahead - the trials.

As a rule, researchers don't begin testing experimental vaccines on people until after rigorous safety checks. It starts with a pre-clinical toxicology study on a laboratory scale that assesses whether a drug is safe to use and is tested on animals. That usually takes three to six months, depending on the study's design.

There are several strategies normally used to develop a vaccine: an inactivated virus, a live attenuated virus, or heavily weaken the virus' strain, and pull out the virus genetic sequence, DNA or ribonucleic acid (RNA).

If the evaluation is successful, the candidates go through to the three phases of testing in people, also known as clinical trials. Each phase has its special treatments, duration and regulations.

The most time-consuming step is testing because researchers have to wait for enough volunteers to be exposed to a virus naturally. The vaccine must be given to a much larger group and compared with an unvaccinated control group to see whether it really prevents the disease. Such a test needs thousands of people to assess the safety and rare adverse events.

The final part before the vaccine can be launched to the market is government approval. We are dealing with a long, complex and expensive process.

CHEAP VACCINE URGENTLY NEEDED

Abdullah Shibli

The Daily Star, Bangladesh

"Vaccine nationalism" is threatening to make it difficult for third-world countries to secure inexpensive and adequate supplies of reliable vaccines.

Vaccine nationalism occurs when a country manages to secure doses of vaccine for its own citizens or residents before they are made available in other countries. The bottom line is, vaccine nationalism will affect the distribution of Covid-19 vaccines, which is likely to be based on high-income countries' purchasing power rather than the risk of transmission.

Not long ago, in a paper in the Harvard Business Review, three scientists expressed their concern over rich countries bankrolling vaccine development and leaving only the crumbs for developing countries. They strongly rejected such nationalistic responses and voiced the need for a centralised, trusted governance system to ensure appropriate flow of capital, information and supplies.

It is expected that a Covid-19 breakthrough could beget off-the-charts expensive treatments. Some of the existing drugs that scientists are testing as Covid-19 treatments have a special status for rare disease treatments, and the price tags to match - prompting early warnings from academics and drug pricing reform advocates that if one is effective, access could be a critical issue.

In the past, most high-income countries turned to pharmaceutical companies within their own borders for production. High-income countries directly negotiated large advance orders for the vaccine, crowding out poor countries.

Although several of those rich countries, including the United States, agreed to make vaccine donations to low-and middle-income countries, they only carried out these donations after ensuring they could cover their own populations first.

But according to WHO director-general Tedros Adhanom Ghebreyesus, "vaccines only realise their true power when they are deployed to protect the poorest and most vulnerable".

PUTIN'S MOVE A MASTERSTROKE

Ramon Farolan

Philippine Daily Inquirer, Philippines

Recently, President Vladimir Putin announced that Russia has granted regulatory approval to a Covid-19 vaccine that showed "stable immunity" against the new virus and had "passed all the necessary checks".

The vaccine named "Sputnik V" was developed by Gamaleya Research Institute of Epidemiology and Microbiology. On Aug 1, the Russians announced that the vaccine passed through Phases 1 and 2 clinical trials. They reported not a single participant of the trials got infected with Covid-19 after being administered with Sputnik V.

The CEO of the Russian Direct Investment Fund that supports the work of the Gamaleya Research Institute, Mr Kirill Dmitriev, announced the start of the crucial Phase 3 trials involving 2,000 people in Russia, the Middle East, and Latin America.

Mass production of the vaccine will be done by Russian business conglomerate Sistema before the end of the year. Mr Dmitriev said Russia has received requests from more than 20 countries for 1 billion doses of the vaccine.

Reactions from the Western world were swift and somewhat sour.

Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, expressed serious doubts that the Russians have actually proven that the vaccine is safe.

Dr Scott Gottlieb, former US Food and Drug Administration commissioner, said much of the testing done was on too small a group. "I will not take it, certainly not outside clinical trials."

Let us ask ourselves this question: Is Mr Putin a madman that he will risk the safety, the good health, the well-being and possibly, the lives of millions of his people just to score political propaganda points and gain some prestige for the nation? He is a lot smarter than some of his rivals on the world stage.

With his announcement, Russia is several steps ahead of China, Japan, the US and the United Kingdom in the race for a vaccine. This will spur everyone to work harder and faster and even come up with a better vaccine than Sputnik V.

Mr Putin's move is a master stroke and his timing is impeccable.

DIVIDING THE WORLD?

Editorial

The Statesman, India

Concerns raised by America's top infectious diseases specialist, Dr Anthony Fauci, about the safety of vaccines being developed by China and Russia deserve to be taken seriously. Russia has claimed its vaccine will be ready next month, but even if this happens, the product is likely to face intense scrutiny around the world. Some 160 candidates, including eight in India, are in various stages of development, with 23 in clinical trials and six in the final, third-phase human trials.

Last month, China announced that a vaccine developed by CanSino Biologics was being used to immunise the nation's military, causing ethical concerns to be voiced by several scientists. Two other Chinese companies, Sinovac and Sinopharm, have commenced final-phase trials in Brazil and the United Arab Emirates, respectively.

These are being watched closely, especially because of China's somewhat dodgy record with vaccines - the most recent aberration having been in 2018 when 200,000 children were administered a defective vaccine for diphtheria, tetanus and whooping cough that caused paralysis in some recipients.

Overall, there is an almost Olympian fervour around the world - ironic in view of the cancellation of the Games - to launch the first vaccine and there are concerns that this frenetic rush may cause some short cuts to be taken, with potentially fatal consequences. There is also an element of near-Cold War-era competitiveness, encapsulated by the Sputnik remark and underscored by allegations that both China and Russia attempted to steal Western coronavirus research.

Three Western vaccine candidates - one produced by the American firm Moderna and the National Institutes for Health; the second by Oxford University and Britain's AstraZeneca and the third by Germany's BioNTech with American company Pfizer - are in final-phase trials.

Dr Fauci's remarks came amid a congressional hearing where he commented: "I do not believe that there will be vaccines so far ahead of us (the United States) that we will have to depend on other countries to get us vaccines."

The search for a vaccine that ought to have brought the world together appears to have further divided it.

 

[Lala81]

The only truth about vaccine is that so far that the one backed by SG will be significantly behind the front-runners. The front runners have all begun or are starting phase III this month. While the Temasek backed one is phase I only.

So we don't know who's the best or the fastest horse, but it won't be the one backed by Temasek. 

[therock]

https://www.nature.com/articles/d41573-020-00151-8

 

The state of the vaccine from one of the top journals:

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The COVID-19 vaccine R&D landscape has developed at unprecedented scale and speed since our initial analysis in April identified 115 candidates in the pipeline (Nat. Rev. Drug Discov. 19, 305–306; 2020). In this updated overview, we focus on candidates in clinical trials and provide some initial perspectives on their clinical development.

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Outlook

Although the leading COVID-19 vaccine candidates have progressed to advanced stages of clinical development at exceptional speed, many uncertainties remain given the lack of robust clinical data so far. Moreover, given the highly unusual circumstances associated with developing a vaccine during the evolution of a novel global pandemic, probability of success benchmarks for traditional vaccine development are likely to underrepresent the risks associated with delivering a licensed vaccine for COVID-19. The most advanced candidates are expected to begin reporting data from pivotal studies over the coming months, which if positive will be used to support accelerated licensure of the first COVID-19 vaccines. Such data will also provide valuable insights for the field and inform ongoing and future development activities aimed not only at controlling the current global pandemic, but also for effective long-term immunization strategies against the disease.

 

Edited September 6, 2020 by therock

[therock]

https://www.channelnewsasia.com/news/world/astrazeneca-puts-covid-19-vaccine-trial-on-hold-over-safety-13093518

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NEW YORK: Pharmaceutical company AstraZeneca on Tuesday (Sep 😎 said it has paused global trials, including large late-stage trials, of its experimental coronavirus vaccine because of an unexplained illness in a study participant.

The vaccine, developed with the University of Oxford, has been widely seen as one of the leading global candidates against the coronavirus, and the suspension of the trial dims prospects for a potential year-end rollout its lead developer had signalled earlier.

AstraZeneca said it voluntarily paused trials to allow review of safety data by an independent committee and was working to expedite the review of the single event to minimize any potential impact on the trial timeline.

"This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials," the company said in an emailed statement.

The nature of the illness and when it happened were not detailed, although the participant is expected to recover, according to Stat News, which first reported the suspension due to a "suspected serious adverse reaction".

The US Food and Drug Administration defines that as an adverse event in which evidence suggests a possible relationship to the drug being tested.

Drug trials have to pass through a few phases to get through:

https://www.nccn.org/patients/resources/clinical_trials/phases.aspx

 

And if there are any adverse reactions, trials can be halted or even cancelled. The pressure to be the first is high, and some companies may take a short cut. So be careful as the time to clinical use typically takes a few years. 

[Datsun366]

On 8/16/2020 at 9:59 PM, Zxcvb said:

Nobody here works in Biopolis? Anyone work in the pharmaceutical industry care to input?

No comment by those on the line.

With requisite knowledge and satelite experience...Mr Moh can tell you...

Fast and relatively safe about another 2 years out.

For those in PH, thats like lacekar fast.

Long term side effects...? Neonatal impact/ susceptibility to cancer/cellular mutation...

Me and my own may take the vaccination five or six years after introduction. That loud and clear?