The state of the vaccines

But you still are not contributing

 

Don't feed the trolls...

 

OK, now get this, folks. As you know from the above posting, AstraZeneca resumed the vaccine trials in the UK, Brazil, and now South Africa too, after a review by the British equivalent of our FDA dismissed the concern raised by the supposed case of transverse myelitis. However here in the United States we are still hesitant. The NIH has launched an autonomous investigation of the matter.

https://www.yahoo.com/news/astrazeneca-covid-19-vaccine-trial-042249323.html

While it is good that our agencies are vigilant, I wonder if ultimately this will mean that the AstraZeneca vaccine will be approved in the UK, Brazil, and South Africa, but not in the United States.

Anyway, apparently they might allow the trial to proceed at some point mid-week, so we'll see.

I think there may be a bit of a political aspect to it, as well. I mean, the British agency, The Medicines and Healthcare products Regulatory Agency (MHRA) is highly reliable and obviously the Brazilians and South Africans took their word for it. But given that our agencies here have been under political attack, accused of possibly rushing approvals due to political pressure, I think they decided to signal to the public, "not so fast."

 

I don't think a vaccine is a problem. We will have by the end of the years several a proofed.

The biggest problem will be production of everything that is needed and that will cost insane amounts of money.
The German government just invested into BioNtech, 234 millions to increase and built the domestic production line.
Germany established a fund of over 1 billion Euro, with which it will make sure that there is a domestic/EU vaccine and production.
I wrote several month ago in Stats statistic thread, that we will see mind boggling amounts of money going into the virus project, this time money or funding do not matter and we will see record time vaccine development.
Were they used to have to beg for money, for this type of research, they are now flooded with money, as we have never seen before.
As sad as the whole c19 crap is, we should look at its bright side.
New technologies like mRNA and so on are getting a rather health shot in the arm. If they work for c19, with little side effects, they might become the next technology against various cancers, or the next pandemic virus.
Very interesting times, I would say.
Centerfield is the medical side, of which I have very little knowledge, just a farmer, but I have always been interested in high tech technologies of all kinds. For a tech freak this is just hogs heaven, we will see a explosion in the vaccine field, because of c19, because right now, Geld spielt keine Rolex, money does not matter.

 

Yes, hopefully the mRNA approach will pay off, but it needs to be understood that an mRNA-based vaccine has never been approved for humans before, and they do carry some risk of ADE or antibody-dependent enhancement. Their efficacy is also still to be determined and is likely to be less robust than the traditional methods. Somehow I prefer the more traditional approaches of inactivated or attenuated virus of virus subunit. But yes, technology must advance, so fingers crossed.

I have no big illusions about the money side. I have nothing against capitalism, I think it ends up being what makes the world move, but I'm under no illusion that anything that is this well funded, is done out of some sort of altruism. There are two drivers of this, in my opinion. One, there are huge profits to be made, given that the whole planet is eager to have a vaccine (or I should say, minus the anti-vaxxers and those who don't trust the process to be truly safe, given the rush). Two, governmental entities know that this pandemic was one of the biggest blows to the world economy, ever. There is nothing more damaging to an economy than an out-of-control outbreak of a deadly disease. So governments and corporations and foundations are interested in investing a lot on this because they know that if they don't the economy will continue to underperform.

But hey, beggars can't be choosers. I'm glad that for a change, there is money being heavily invested in making these vaccines.

By now I don't doubt that we will have several vaccines ready by the at most early 2021. Another problem, though, is to get it to the population. Even the glass vials used to transport the vaccine will be in short supply, not to forget that some of these vaccines need ultra-low temperature for transport and storage (in the case of the Pfizer one, minus 94 degrees F). So, just having the vaccine ready and approved is not the whole story. Also, getting a significant chunk of the population to accept it may be an uphill battle.

 

The Feds remain concerned about the AstraZeneca vaccine.

https://www.thedailybeast.com/feds-...eneca-covid-19-vaccine-side-effect?ref=scroll

Like I was saying, if there is another case of transverse myelities, it will be the end of the line for them. Fortunately the first case was rather unrelated MS.

 

What intrigues me about the MRNA, they actually trying to create a path, pipeline to the offending virus or disease, or cause and they are trying to teach our body how to defend it self.
That targeting.
30 years ago I had cancer and they threw everything and the kitchen sink at you and than the fridge. It was than the question what would kill you, cancer or the treatment, it was 50:50 or even worth.
I sliped barely by. Survived because of youth and being a international top athlete, but just barely. If I had not been in that supreme shape, I would have not survived the treatment and because of my doctor, who convinced my me that giving up was no option, none at all.
I just had held the hand of my father, who died of cancer. 3 month before, when I was diagnosed.

I think this virus will lead into a explosion of new technology. It will revolutionize medicine. It needs money, gigantic amounts of money to bring those future technologies to the front.
Maybe when we look back in 10 years, we will understand what c19 has done to that field and how we as people profited from it.
Finding new ways to fight so many horrible deceases, like cancer, or AIDS

 

Yes, let's hope so.

 

Moderna has enrolled so far 25,296 volunteers, and 28% are racial minorities. These are numbers that are acceptable to the FDA. So they only need less than 5,000 more to complete the 30,000 they need, and will also need a few more weeks to give the second dose to the volunteers (28 days later) then 2 weeks for antibody production so that the incidence of natural infection can be gauged (no case can be counted before two weeks after the second dose). They've managed to give the second dose to 10.025, so far.

A few more weeks to complete the 30,000, then 4 more weeks for the second dose, then 2 more weeks to start counting natural infection to compare to those who got vaccinated, we're looking at something like two and a half months from now. So, it won't be before December, for Moderna. By January they should have finished. This, of course, if no glitch happens like the one that delayed AstraZeneca.

 

News on the Moderna phase 3 trial:
The company expects a first safety read-out in November. Given their existing number of enrolled subjects, to meet the FDA threshold for Emergency Use Authorization the company would need to see 53 cases of Covid-19 to trigger the first safety read-out by the monitoring board, and most of these would have to be found to be occurring among the placebo group. If this happens, the company does plan to file for a limited EUA.

The company says they are under no pressure from the Federal Government to move faster (but of course they have a financial interest in moving faster in terms of positioning themselves in the vaccine market, with their main competitor Pfizer seeming to be farther along). The CEO did say "we don't want to have the first vaccine, we want to have the best vaccine" and speaking to investors, he said that a few weeks of delay will not affect the company's bottom line. They continue to produce the vaccine to be ready to launch immediately if they earn regulatory approval.

The FDA establishes an efficacy threshold for vaccines of 50%. Moderna is spontaneously setting their bar at 70%. They said that if they achieve that, they will apply for the EUA.

Moderna's application would be limited, and only include in this first phase, healthcare workers and the elderly.

Moderna needs about 4,800 more volunteers to complete their phase 3 trial with 30,000 subjects.

Pfizer, which voluntarily increased the size of their phase 3 trial to 44,000, has enrolled 29,000 people. So, due to their spontaneous upgrade, they need more people to complete the trial than Moderna, although they have enrolled almost 4,000 more people than Moderna, already. They could be 1,000 people from the finishing line but they decided to push it to 15,000 more. You may conclude that this will delay then, but not necessarily, because they have a much larger infrastructure and much more experience with these trials, and have international sites. I still think that Pfizer will cross the line first, barred adverse reactions.

 

Sinovac's CoronaVac vaccine, which is sailing beautiful towards regulatory approval in Brazil (with 98% immunogenicity and no serious side effects so far) is expected to be available in Brazil already in October (5 million doses, therefore enough to immunize 2.5 million Brazilians) and by December the expectation is of 46 million more; that is, enough for 23 million people, therefore a total of 25.5 million people by the end of the year. These will be all for residents of the State of São Paulo given that the vaccine will be produced by the Instituto Butantan, a Sao Paulo State organization. Their agreement with Sinovac includes the transfer of technology so that the Instituto Butantan, Brazil's largest vaccine maker, will be producing the vaccine domestically. The Butantan is expanding its production capacity and building a new wing just to make CoronaVac, which will be ready by the end of September.

The State of São Paulo has 44 million inhabitants. So 58% of the population will get the vaccine. This, added to the ones naturally immune from the natural infection, should be enough to achieve herd immunity at least for the susceptible population, given that 22% of the São Paulo population is made of children aged 0-14; I assume they will not receive the vaccine in this first phase. After they finish vaccinating all State of São Paulo residents who want the vaccine, they will deliver their vaccine to other Brazilian states.

So, it looks like their equivalent of the Warp Speed initiative will be more successful than ours, in the United States.

Brazil also has agreements with Oxford/AstraZeneca and with Gamaleya, so other states will benefit from their vaccines too. Gamaleya is collaborating with Fiocruz, the other big biotech Brazilian organization, headquarterd in Rio de Janeiro, the country's second biggest city after São Paulo City.

I expect that Brazil will immunize the bulk of its population way ahead of the United States. Their position of members of BRICS helps them with access to the Chinese and Russian vaccine makers. I trust the soundness of the CoronaVac safety and efficacy data because it's been confirmed by the Instituto Butantan. I'm more skeptical of the Gamaleya vaccine but the Fiocruz is good too.

 

The combined populations of the BRICS nations comes to just over 3 billion people. Using the Sinovac vaccine only that would mean 6 billion doses. How long will it take to manufacture that many doses?

 

A long time. But I'm talking about transfer of technology; both the Instituto Butantan and the Fiocruz will make their vaccines domestically so they should have enough for Brazil's 220 million inhabitants. Both organizations are experienced with making millions of vaccine doses; they have the production facilities, the vials, and the distribution infrastructure through SUS (Sistema Unico de Saude, their universal healthcare system; it helps that neither the CoronaVac nor the Sputinik V need very low temperatures for storage and handling). So I'm confident that Brazil will be fine, and soon. Russia's population is not that large either and they have already started with their Sputinik V vaccine. So I expect Russia and Brazil to get their people vaccinated before the US, India, and China. I don't know anything about the situation in South Africa.

 

Check out the Covid19 Tracking thread. Seems like Russia is seeing increases instead of decreases.

Brazil getting their act together can only be a positive for them since they have been hit hard. India has a LOT of drug manufacturing capacity so I expect them to be able to produce their own vaccines assuming that Modi can sort out something with Xi. I doubt that Russia will accept the SinoVac for political reasons and the last I heard South Africa was participating in the Oxford Astra Zeneca trials so they might have to wait for that one.

 

Well, Russia actually said they'd start mass vaccination at some point in October if I'm not mistaken so we haven't seen the effect of their vaccine yet. Yes, you're right that South Africa is one of the sites for the Oxford/AstraZeneca phase 3 trials. This often comes with agreements for vaccine delivery in case of approval.

 

Seems like the administration might be looking at approving a vaccine before Election Day, contrary to FDA advice:

https://news.yahoo.com/signs-october-vaccine-surprise-alarm-175348593.html

 

After some quiet days in terms of vaccine news, we have a major one to announce: Johnson & Johnson has started phase 3 trials of their adenovirus-vector (serotype Ad26) Covid-19 vaccine. The trial will have up to 60,000 participants (more than any other, which is good) and is being started in the United States, Argentina, Brazil, Mexico, Peru, Chile, Colombia, and South Africa.

The big novelty here is that this vaccine will be studied with only one dose. This is helpful in two ways: the trial will go faster, and if one dose works, the number of vaccines produced will be equal to the number of people immunized instead of cutting the latter in half due to the need for two doses. The company is promising to deliver 1 billion doses in 2021. They expect to be ready to deliver the first doses (if they earn regulatory approval) at some point in "early 2021."

A separate trial will exist in the UK, studying 2 doses.

Johnson & Johnson of course is a company with vast infrastructure and resources (see their ability to engage in several countries for the trial, and the large number of subjects they are aiming for), and they have already used the same AdVac platform successfully for their European-approved Ebola vaccine, and for their Zika vaccine candidate. So it's not unproven technology like the mRNA vaccines. The use of Ad26 is good; it's a less common strain therefore fewer people's immune system will compromise the efficacy of this vaccine. The name of the J&J vaccine is Ad26.COV2-S. Their phase 1/2 trials were done in the US and Belgium and involved over 1,045 subjects, so also a bit larger than other phase 2 trials.

Johnson & Johnson is one of the companies being supported by the Warp Speed initiative. Unlike Pfizer they did accept the US Government's money, so this bodes well for priority distribution of their vaccine (if approved) in the United States.

A phase 3 trial with 60,000 volunteers might earn the good will of those who are suspicious of what they (wrongly) interpret as safety corners being cut (they are not, for all makers except Gamaleya), and the one-dose approach will be good for distribution and vaccination logistics.

Therefore, these are very good news. The only glitch for me is that I tried and tried but was unable to locate any statement by the company or any published result in the scientific press about immunogenicity of this vaccine in its phase 1/2 trials. I found the pre-clinical studies in hamsters and primates and they are encouraging, but I couldn't find the percentage of seroconversion in humans. One wonders why... isn't it as good as others and therefore the company is silent about it?

If somebody finds this information and posts it here, it's appreciated.

 

I found the information on the Johnson & Johnson vaccine's efficacy: the phase 2 trials found 98% of neutralizing antibodies. Impressive.

 

The vaccine news front has been quiet lately but there was an important development. Moderna has published in the NEJM a subset of their data for phase I for older adults, age 56 to 70 and 71 and older, and in both groups, the higher dose of 100 micrograms 28 days apart produced neutralizing antibodies in similar percentage as the younger adults, which is very good news because there is the possibility that those who need the vaccines most, the older adults, would not have their weaker immune system stimulated the same way by the vaccines.

Side effects were comparable to those experienced by this same population when they take the high dose flu shot, that is, headache, fatigue, body aches, chills and injection site pain, which were deemed mainly mild to moderate except for two subjects, one who developed fever of 102.2, and one who developed transient severe fatigue. Both recovered fine. This is a small subset of subjects, only 40 of them. Phase 3 does incorporate more older people taking the 100microgram dose so we'll see, but this is good news for the seniors out there.

 

What about the idea of picking the most promising and go ahead and start making them, seriously expensive if potential fail, if it doesn't pass. Thing is we unwashed types don't know exactly what it means when one of those manufactures believes they will have one that could pass in October, the time it takes after FDA approval to make enough doses. The actual costs, and our country is already is serious debt. Thing is though, it's a gamble, if no fall or winter surge is going to happen, a fail and having to spend the money twice would be seen as an epic blunder, if it worked though, we may never know if it prevented a winter surge. Either way the gambler is cursed by one side or the other.

 

This is already being done. Part of the Warp Speed initiative is what is called cost-sharing, with these vaccine makers already producing the doses in anticipation of approval, something they would never do without this cost-sharing support. It also means that we've already paid for these vaccines, and if they get approved and delivered they will come at no additional cost, initially, for the contracted number of doses. There are options to purchase more in the future.

No, we WILL know if the vaccines are effective; that's what Phase 3 trials will prove, regardless of winter surge or not. If the vaccines are safe and effective as per phase 3 results, then they are safe and effective. Period.

 

I'm still confused.

Sometimes it's hard figuring out what they mean by "eventually successful," or "eventual vaccine." In unwashed terms the vaccine already exists, they are testing it right now, there is "eventually successful," but like a Harley Pan American exist so does the "eventual vaccine," it's just not manufactured in numbers and released to the dealer, held in fridge for D-day, as in they get the equipment...ready to make millions upon millions of doses of such and such but all those millions, including my dose, doesn't roll off the line before "FDA" success? What I am suggesting is make the best prospect, send it to the dealers, and then the day FDA approves becomes Distribution day; if it fails, dump it. Probably everything I said here makes no sense; if it doesn't just ignore it.

“The federal government is making investments in the necessary manufacturing capacity at its own risk, giving firms confidence that they can invest aggressively in development and allowing faster distribution of an eventual vaccine. Manufacturing capacity for selected candidates will be advanced while they are still in development, rather than scaled up after approval or authorization. Manufacturing capacity developed will be used for whatever vaccine is eventually successful, if possible given the nature of the successful product, regardless of which firms have developed the capacity..” https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html

 

They are saying eventually successful because no vaccines have passed Phase 3 yet. Like the Oxford/AstraZeneca case has demonstrated, it is sufficient to have one serious reaction to throw a wrench in the process. So we hope that eventually one or more of the vaccines will pass Phase 3 and will be approved. Distribution and storage are complicated, so it's best to keep manufacturing but to start distribution only once there is regulatory approval. There are currently 9 vaccines in Phase 3. It wouldn't be practical or feasible to start distributing and storing them already in the point of care. We need to wait and see what the eventual winner(s) will be, not to duplicate or triplicate or quadruplicate etc a very logistics-consuming operation.

 

The Phase 3 CoronaVac trial is scheduled to conclude in Brazil on October 15th. It seems like it will be the first Phase 3 conclusion in the world, just a couple of weeks from now. Preliminary results are so good that the Brazilians are very confident that the vaccine will be approved by their FDA-equivalent (called ANVISA) and they have scheduled the start of vaccination for the population: December 15th (starting with healthcare workers). This vaccine has shown 97% to 98% effectiveness including in the elderly, and no serious side effects, so far. It's been a complete success. While it is hard to trust the Chinese, I have had phone contacts with colleagues from the Instituto Butantan and they have confirmed to me that the data are solid and legitimate, and I do trust them (very competent and well-trained people, very serious folks; the Butantan has an excellent international reputation).

The CoronaVac, a joint effort of the Chinese vaccine maker Sinovac and Brazil's biggest vaccine maker Instituto Butantan, looks like a true winner. It uses the traditional method of inactivated virus, the real thing, unlike the unproven mRNA technology.

Technically it is not the first one but I wouldn't count Gamaleya's Sputinik V because they cut corners - they were the only makers/country to do that: approved it ahead of phase 3, and they seem to have falsified data when they reported their phase 1/2 results.

If the CoronaVac is approved and starts being distributed on December 15th, it will indeed have achieved the previously unheard-of less-than-one-year timeline, from R&D to testing to approval to distribution to immunization. Initially, I frankly never thought that it would be possible, but it looks like they've pulled it off. This is truly remarkable, and is a response to the nay-sayers who kept accusing the international medico-scientific community of not knowing/doing much about this virus. To put it in perspective, the average time to get a new vaccine to the market is ten years, and the shortest previous time ever, was 4 years.

It is also interesting that the likely first vaccine to finish up phase 3, get approved, and start regular distribution was NOT part of the US's Warp Speed Initiative...

So, China and Brazil got it done apparently faster and better than our Warp Speed Initiative, which is kind of a blow to our feelings of superiority and exceptionalism.

 

Thanks. It does seem super complicated.

With all the people going back to social gathering places and Phase 3 openings they could live without; with the Brazilian scenario, about two months from the time of approval to some distribution, potentially lots of bad when people are inside up north and can't open bar and restaurant doors and windows. Out door cafes and Antarctic winter gear...

People should just freaking wear a mask...and get used to it.