Coronavirus

[Mr._Clark]

Here's some good news. The early numbers out of Isreal suggest that the Pfizer vaccine is highly effective after the second shot kicks in.

So far It's basically 100% effective in preventing hospitalization (granted, there is no control group).

>>>Maccabi said it has 128,600 members who have seen seven days pass since full vaccine protection kicked in — and only 20 have caught the coronavirus after they were considered immunized. . . . none of the 20 vaccinees was hospitalized or suffered from a fever higher than 38.5 degrees. <<<

In week after 2nd Pfizer vaccine shot, only 20 of 128,000 Israelis get COVID

Figure represents 0.015 percent of people, indicating vaccine is hitting 95% efficiency rate predicted by clinical trials; top immunologist hails 'exciting results'

www.timesofisrael.com

 

[davidscott]

Well I'm 65 and just got my first covid shot (Moderna) and I'm happy with maybe 50 - 60% after 14 days. I am scheduled for a second dose in February. I will still wear a mask and distance for the foreseeable future. Be safe and realize that this thing is dangerous.

 

[TLS Guy]

According to the NYTimes, the Novavx vaccine is effective except not against the South African variant. The article also states that many people who already had COVID-19 were reinfected.

"Not encouraging" is one way to put it.

Hopefully the J&J vaccine is more effective against the SA variant.

>>>Novavax, which makes one of six vaccine candidates supported by Operation Warp Speed last summer, has been running trials in Britain, South Africa, the United States and Mexico. It said Thursday that an early analysis of its 15,000-person trial in Britain revealed that the two-dose vaccine had an efficacy rate of nearly 90 percent there. But in a small trial in South Africa, the efficacy rate dropped to just under 50 percent. Almost all the cases that scientists have analyzed there so far were caused by the variant, known as B.1.351. The data also showed that many trial participants were infected with the variant even after they had already had Covid-19. . . .

The fact that three vaccines all appeared to show lowered effectiveness against the variant from South Africa is not encouraging, and the results Novavax announced Thursday were the first to occur outside of a laboratory, testing how well a vaccine worked in people infected with a new variant. Johnson & Johnson is also on the cusp of announcing results of its Covid-19 vaccine trials, and has also tested its candidate in South Africa. <<<

Covid-19 Live Updates: Novavax’s Vaccine Works Well Except on Variant First Found in South Africa

That variant has now been found in the United States. New York severely undercounted virus deaths in nursing homes, a state attorney general’s investigation concluded. The European Union has locked horns with drug makers over delivery problems, and Germany said its shortage of doses could last...

www.nytimes.com

Novavax is also a novel platform. In essence it is a synthetic killed vaccine platform. Like most killed vaccines it contains an adjuvant to increase effectiveness. They call the synthetic viral antigens nanoparticles. I think though, that title was given by some MBA/marketer, who happened to know that name and thought it sounded impressive.

If it is true that it is ineffective against the SA variant, then that is bad news, as it will encourage more rapid spread of that variant. I would have thought that technology would be reasonably easy to edit, but I don't know that.

Both Moderna and Oxford are editing for the SA and the dangerous Brazilian mutations.

As I have said before, we are in a race against time. We need to build vaccine plants like has never been done before. I think only India, as a nation, really understands that. If we do not do this, and roll out is slow, we will guarantee the proliferation of vaccine resistant variants.

India is reporting a decline in cases. The news from Africa is dire, where the pandemic seems to be accelerating fast. American news media, need to be reporting on this pandemic much more as a global issue than a national one, or populations will get blindsided and surprised. This could result is massive lack of confidence.

 

[Irvrobinson]

There's a fascinating article that just appeared on the Wall Street Journal website, though I suspect it can't be read without a subscription:

Behind AstraZeneca’s Covid-19 Vaccine Stumble

AstraZeneca’s CEO promised more shots, at a lower price, than competitors, but now faces criticism from the EU for a production shortfall.

www.wsj.com

Apparently AstraZeneca is using contractors around the world to produce their vaccine, much like many fab-less chip design companies (e.g. Apple) use contract fabricators like TSMC to actually manufacture their chips. The AstraZeneca contractor in Belgium ran into a yield problem, due to the sensitivity of growing a chimpanzee cold virus in human kidney cells (EUV lithography for chips has nothing on the weirdness of biology). The process is apparently very delicate, so it naturally involves maximum precision and refinement, and making these processes reliable and predictable is unlikely to happen without glitches. Complicating matters more, just like Pfizer and Moderna, the vaccines are produced by multiple contractor companies in multiple countries, including the US, for example. AstraZeneca's contract manufacturer's yield issue (this so reminds me of chip manufacturing) which is what reduced finished vaccine supplies. Combined with the longer manufacturing time for a dose of the AstraZeneca vaccine, as compared to the mRNA vaccines, the low yields mucked up the production pipeline for a longer period of time in the AstraZeneca case. The article says other AstraZeneca contractors are not seeing the same problem.

Nonetheless, apparently the EU bureaucrats that chose AstraZeneca and took their sweet time compared to the UK in placing orders are now embarrassed by the resulting reduction in production. Threatening speeches followed. I would say let's hope Moderna, Pfizer, and J&J are going to do better, but from a few searches I've done they all appear to use manufacturing subcontractors for vaccines on a worldwide basis. None of this surprises me, given the sensitivity of the processes and the complexity of production, so to quote a line from "Jurassic Park", I think we should all "Hold on to our butts!" and hope this glitch is just one of only a few we'll see.

 

[TLS Guy]

There's a fascinating article that just appeared on the Wall Street Journal website, though I suspect it can't be read without a subscription:

Behind AstraZeneca’s Covid-19 Vaccine Stumble

AstraZeneca’s CEO promised more shots, at a lower price, than competitors, but now faces criticism from the EU for a production shortfall.

www.wsj.com

Apparently AstraZeneca is using contractors around the world to produce their vaccine, much like many fab-less chip design companies (e.g. Apple) use contract fabricators like TSMC to actually manufacture their chips. The AstraZeneca contractor in Belgium ran into a yield problem, due to the sensitivity of growing a chimpanzee cold virus in human kidney cells (EUV lithography for chips has nothing on the weirdness of biology). The process is apparently very delicate, so it naturally involves maximum precision and refinement, and making these processes reliable and predictable is unlikely to happen without glitches. Complicating matters more, just like Pfizer and Moderna, the vaccines are produced by multiple contractor companies in multiple countries, including the US, for example. AstraZeneca's contract manufacturer's yield issue (this so reminds me of chip manufacturing) which is what reduced finished vaccine supplies. Combined with the longer manufacturing time for a dose of the AstraZeneca vaccine, as compared to the mRNA vaccines, the low yields mucked up the production pipeline for a longer period of time in the AstraZeneca case. The article says other AstraZeneca contractors are not seeing the same problem.

Nonetheless, apparently the EU bureaucrats that chose AstraZeneca and took their sweet time compared to the UK in placing orders are now embarrassed by the resulting reduction in production. Threatening speeches followed. I would say let's hope Moderna, Pfizer, and J&J are going to do better, but from a few searches I've done they all appear to use manufacturing subcontractors for vaccines on a worldwide basis. None of this surprises me, given the sensitivity of the processes and the complexity of production, so to quote a line from "Jurassic Park", I think we should all "Hold on to our butts!" and hope this glitch is just one of only a few we'll see.

Irv, you are absolutely correct. Part of the problem is the subcontractor sites are not purpose built. For best results the plants need to be purpose built. Outside the UK the only one that is the Indian Pune plant. As far as I can tell that is doing well.

The UK have the advantage in getting this difficult manufacturing process of the ground. Remember neither the mRNA, mDNA vaccines or the synthetic antigen vaccines have ever been manufactured before. So this is highly complex and novel. In addition huge quantities are required urgently. However the UK for the Oxford vaccine have a plant right there at Oxford, and another one nearly complete. Professor Green of the Jenner institute worked out the manufacturing process. She is a real "character" by the way. She will be supervising the correction of problems and glitches right there in Oxford you can be certain.

 

[Swerd]

Probably the biggest problem in biopharma is scaling up from research laboratory level molecular biology to large scale production. Nearly all the equipment is different, especially the methods used for growing cells in very large volumes. Because viruses are grown on cells, such as the cloned human kidney cells, the final yield depends entirely on the status of those cells. Those cells must not be infected by other micro-organisms, such as mycoplasma, or other viruses, known or unknown.

The earliest Salk polio vaccine was grown on African Green Monkey (rhesus monkey) kidney cells. The yield was adequate, but those cells were also infected with an unknown (at the time) monkey virus, called SV40. Everyone immunized with the early Salk polio vaccine was also inoculated with active SV40 virus. In 1960 it was discovered, to everyone's horror, that SV40 caused tumors in rats and mice. But not in humans. A lot of sleep was lost over that until the 1990s when it was clearly shown that people who received early Salk vaccine have not developed tumors at unusually high rates.

Now take a further step in difficulty, and try to replicate one successful large scale production plant into several others. It's a chemical engineer's nightmare. You can copy everything down to the nuts & bolts, and still run into numerous problems. The obvious problem is poor yield. Even worse is when large amounts of the product can be made, but it is biologically inactive. Such problems do exist and are not uncommon.

That's why it was so wrong for execs of big pharma and politicians to make such bold promises about vaccine availability.

 

[Trell]

Coronavirus: Germany recommends against using AstraZeneca jab for over-65s – as it happened

www.ft.com

"Germany recommends not using AstraZeneca jab for over-65s​

​

Guy Chazan​

The German authorities have recommended that the OzAstraZeneca vaccine against Covid-19 should not be used for people aged over 65.​

A statement by the Standing Vaccine Commission at the Robert Koch Institute, Germany's main public health agency, said there were "insufficient data currently available to ascertain how effective the vaccination is above 65 years".​

For that reason, the commission recommended that it only be used for people aged between 18 and 64.​

The RKI said that the two vaccines that had been approved by the EU authorities - from BioNTech/Pfizer and Moderna - were judged to be "equivalent in terms of safety and efficacy".​

"​

More information on the back-and-forth along with finger pointing:

German experts back age limit for AstraZeneca jab, adding to EU’s woes

Europe’s most populous country could avoid giving the vaccine to vulnerable age groups.

www.politico.eu

 

[Mr._Clark]

I'm assuming most people have seen news reports about the J&J vaccine trial results. Faucci is quoted in a CNN article (link below) as saying that a two-dose regimen might significantly increase the efficacy.

Given that the J&J vaccine uses an Ad26 vector, I'm curious how effective a second jab would be given that people apparently develop antibodies to the vaccine itself after the first jab. According to TheScientist (link below), the Russians use different vectors in the two jabs in an effort to avoid this:

>>>The Russian Sputnik V vaccine . . . starts with a shot of Ad26 vector followed by a booster with Ad5, both of which carry the gene for the spike protein of SARS-CoV-2. This circumvents a downside of viral vector vaccines, specifically, once you give the first shot, subsequent injections will be less efficacious because of antibodies against the vector. Ertl says she has no idea of the proportion of the Russian population with Ad26 or Ad5 antibodies, and there seems to be little or no published data from countries that have expressed interested in this virus, such as Venezuela and the Philippines.<<<

More generally, I find myself wondering how effective future vaccines for new viruses would be if the same vectors were to be reused. For example, if a high percentage of the population receives the J&J COVID vaccine using an Ad26 vector now, what would happen if a future vaccine for a new virus relied on the same Ad26 vector? My initial impression was that a vector-based vaccine "platform" (not sure if that's the right word) could be quickly modified as required for future viruses, but the potential for host immunity to the vector makes me wonder about it.

Johnson & Johnson Covid-19 vaccine is 66% effective in global trial, but 85% effective against severe disease, company says | CNN

Johnson & Johnson's Covid-19 single-shot vaccine was shown to be 66% effective in preventing moderate and severe disease in a global Phase 3 trial, but 85% effective against severe disease, the company announced Friday.

www.cnn.com

Vector-Based Vaccines Come to the Fore in the COVID-19 Pandemic

Adenovirus vectors deliver the genetic instructions for SARS-CoV-2 antigens directly into patients' cells, provoking a robust immune response. But will pre-existing immunity from common colds take them down?

www.the-scientist.com

 

[Mr._Clark]

I'm assuming most people have seen news reports about the J&J vaccine trial results. Faucci is quoted in a CNN article (link below) as saying that a two-dose regimen might significantly increase the efficacy.

Given that the J&J vaccine uses an Ad26 vector, I'm curious how effective a second jab would be given that people apparently develop antibodies to the vaccine itself after the first jab. According to TheScientist (link below), the Russians use different vectors in the two jabs in an effort to avoid this:

>>>The Russian Sputnik V vaccine . . . starts with a shot of Ad26 vector followed by a booster with Ad5, both of which carry the gene for the spike protein of SARS-CoV-2. This circumvents a downside of viral vector vaccines, specifically, once you give the first shot, subsequent injections will be less efficacious because of antibodies against the vector. Ertl says she has no idea of the proportion of the Russian population with Ad26 or Ad5 antibodies, and there seems to be little or no published data from countries that have expressed interested in this virus, such as Venezuela and the Philippines.<<<

More generally, I find myself wondering how effective future vaccines for new viruses would be if the same vectors were to be reused. For example, if a high percentage of the population receives the J&J COVID vaccine using an Ad26 vector now, what would happen if a future vaccine for a new virus relied on the same Ad26 vector? My initial impression was that a vector-based vaccine "platform" (not sure if that's the right word) could be quickly modified as required for future viruses, but the potential for host immunity to the vector makes me wonder about it.

Johnson & Johnson Covid-19 vaccine is 66% effective in global trial, but 85% effective against severe disease, company says | CNN

Johnson & Johnson's Covid-19 single-shot vaccine was shown to be 66% effective in preventing moderate and severe disease in a global Phase 3 trial, but 85% effective against severe disease, the company announced Friday.

www.cnn.com

Vector-Based Vaccines Come to the Fore in the COVID-19 Pandemic

Adenovirus vectors deliver the genetic instructions for SARS-CoV-2 antigens directly into patients' cells, provoking a robust immune response. But will pre-existing immunity from common colds take them down?

www.the-scientist.com

Another related question is if an adjusted booster shot for a COVID variant uses the same vector as the first jab, will the booster be effective?

It appears to me that the Russians are basically screwed if a COVID variant escapes the initial two jabs because they don't have any other vectors for a booster (I realize this is a moot point if the first two jabs prove to be ineffective).

 

[Swerd]

Thanks for that link to the article on Vector-Based vaccines. It's a good explanation to this complex problem with adenovirus or other vectors, such as attenuated measles virus. One of the advantages of the mRNA vaccines is that they avoid using such virus vectors. They however do pay a price of poor stability requiring deep freezing to avoid degradation. There is almost certainly a serious effort going on now to find ways to improve stability of mRNA vaccines.

The article also mentions the approach the Russians used in their Sputnik vaccine, where the 1st dose used an Ad26 vector and the 2nd dose used Ad5 as the vector. Perhaps there can be experiments combining different vaccines into a 2-dose method, such as an adenovirus vector vaccine for one dose and a mRNA vaccine for the other. This will require cooperation among the different competing vaccine manufacturers. I know for a fact that the US Government, via the NIH and the NCI, has done this successfully in the past. I believe that the NIAID should be able to do this too, if it hasn't already done it.

 

[Swerd]

In addition to the good news from J&J, Novovax reports 89% efficacy in an Interim Analysis of it's clinical trial.

Novavax COVID-19 Vaccine Effective, But Less So Against Variant In South Africa

Novavax says its COVID-19 vaccine is 89% effective at preventing illness, according to an interim analysis of a U.K. study. But the vaccine wasn't as effective against some viral variants.

www.npr.org

 

[Swerd]

In the Washington Post this morning, I read an interview with Stanley Plotkin the famed vaccinologist. He’s retired, but sits on Moderna’s board of directors. He too has had great trouble getting vaccinated.

https://www.washingtonpost.com/nation/2021/01/27/expert-covid-vaccine/?arc404=true

“I’m 88 years old. I’m in the priority group, and I qualify by all the Phase 1 recommendations. That should be enough. I don’t want to jump ahead of anyone in the line. I don’t want to call somebody up on the phone and say: “You know, I actually consulted on this vaccination process. I wrote the textbook on vaccines.”

“If I’m not able to get in through normal channels, that means a lot of people like me are not getting in. That’s a big problem. We shouldn’t be experiencing this level of chaos in a developed country at a time like this. I live in a suburb of Philadelphia, Doylestown, so it’s not like I’m way out in the hinterlands. I did research online and registered for all sorts of things with the state and county, and I never heard back. I called and called and couldn’t find a way to get vaccinated within 20 miles of my house. My wife got frustrated on my behalf and started searching outside the area, and just by chance a few days ago she found a hospital in a different town that had openings left for the Moderna vaccine. I’ve barely left home to get the newspaper, but I was lucky to find this vaccine anywhere. I realize a big part of the problem is the lack of supply, but millions of people are being left on their own to navigate this disorganized mess. It’s a free-for-all. What kind of system is that?”

That is exactly what my wife & I have faced.

 

[GO-NAD!]

In the Washington Post this morning, I read an interview with Stanley Plotkin the famed vaccinologist. He’s retired, but sits on Moderna’s board of directors. He too has had great trouble getting vaccinated.

https://www.washingtonpost.com/nation/2021/01/27/expert-covid-vaccine/?arc404=true

That is exactly what my wife & I have faced.

Still, despite the complaints about access to vaccination in the US, you are doing quite well compared with the rest of the world.

 

[panteragstk]

Still, despite the complaints about access to vaccination in the US, you are doing quite well compared with the rest of the world.

 

[TLS Guy]

So, more good news. We have another two good vaccine candidates, one that uses a viral vector and one that does not.

The issue of immunity to a viral vector is a big problem. Prof. Gilbert has proposed giving those that had the Oxford vaccine for the first immunization series, be given the Sputnik vaccine for the next round. Now the J & J would allow for three rounds.

The reason for proceeding down the viral vector route, is that many, including myself, where very skeptical that injecting a large does of mRNA intramuscularly would work. They fact that it works so well is really good news. However their fragility requires urgent improvement.

I think it is for this reason that the new Oxford facility is being designed to produce mRNA and mDNA vaccines.

Meanwhile the UK is now injecting nearly half a million doses a day. If that can be kept up the the UK should get vaccine herd immunity by September 1. In addition the UK has now signed enough contracts to vaccinate the whole UK population twice over. The UK government says that when the UK population is vaccinated it will give the surplus away, to where it is needed. That is likely to end up being the EU.

The Belgians allowed their police to be used by the EU commission to raid the Astrazeneca factory yesterday. The Germans as usual are resorting to form, and getting increasingly "mouth and trousers" about it.

The EU commission has now threatened to invoke article 122 of their war powers act and take over the factory by force. Apparently the Belgians say they will not allow their police or security forces to be used further by the EU against the plant. Remember the Belgians have suffered mightily twice under the German Jackboot.

The UK government has wisely been pretty silent on it all, and made vague noises of assistance when able, while hoovering up vaccine supplies which the EU commission seem incapable of. I think though that if article 122 was invoked and carried out, a very serious incident would come about. I suspect the UK would defend its interests, especially so, if the Belgians asked for assistance. If that happened I would expect a swift and severe visit from the SAS, who are about the most fierce fighting group of cut throats on the planet when provoked. There is just too much past history with Germans invading Belgium to let that pass. It was that act by Germany that lead to the first WW. They also disrespected Belgian neutrality in the second WW, to get round the back of the Maginot line.

From what I can tell from the comment columns in all UK newspapers, the UK population is in a more Bellicose mood than I have ever known in my lifetime. So if push came to shove, it would be impossible for a British prime minister not to bring the hammer down forcefully.

In addition the EU have today abrogated the terms of the Brexit agreement in Northern Ireland. The border between the Irish Republic and Northern Ireland was a huge bone of contention, between the UK and EU. The Good Friday agreement that brought peace to NI, specified there be no hard border between the two nations. This has lead to a border in the Irish Sea, whereby NI operates largely under EU rules. It is complex and awkward in the extreme. However today, the EU has imposed a hard border for vaccines between the Republic of Ireland and Northern Ireland in contravention of the Brexit agreement that is only just over a month old. This is because they are paranoid about vaccines in the R of I getting into NI.

Hopefully this will de-escalate fast. However there are are lot of EU countries making Bellicose noise, especially Germany and Spain.

All the while other EU countries are making side deal against the rules. For instance Hungary has done a deal with Russia for the Sputnik vaccine and ordered vaccine from China. Neither are approved by the European regulator. By the way, the EU regulator did approve the Astrazeneca vaccine today, but Germany says it will only give it to those under 65. I don't think they will see much of that vaccine anyway. The UK has a cast iron contract which gives them precedence, and will not be sending UK made vaccine to the EU any time soon. I understand that the human kidney cell line at the Belgian plant which is used to culture the Monkey Adenovirus is in serious trouble and may have died off. That is the reason for the two the three month delay in production there.

The UK is still owed 3.5 million doses of the Pfizer vaccine from their Belgian factory. However, it looks that the UK has a robust enough supply chain of vaccines, it would not need to make a big issue of it.

 

[GO-NAD!]

I can't view that video here. No idea what it is.

 

[panteragstk]

I can't view that video here. No idea what it is.

Stupid geographic restrictions...

It was great I assure you.

 

[TLS Guy]

Here is a video of an EU official babbling about transparency at the same time delivering a thinly veiled threat.

 

[trochetier]

................

India is reporting a decline in cases. The news from Africa is dire, where the pandemic seems to be accelerating fast. American news media, need to be reporting on this pandemic much more as a global issue than a national one, or populations will get blindsided and surprised. This could result is massive lack of confidence.

So is US. It is likely because the virus is running out "fuel" for now, i.e. those most susceptible got it and recoverd or died. Similar happened with Spanish flue pandemic.

 

[TLS Guy]

So is US. It is likely because the virus is running out "fuel" for now, i.e. those most susceptible got it and recoverd or died. Similar happened with Spanish flue pandemic.

I think it is far more likely that people are being much more careful. I know they are round here.

The other thing is that we have a fairly low incidence, I think, of the more infectious strains. So data shows it takes these variants about two months to become absolutely catastrophic. If we can not roll out the vaccine fast, we will have the worst part of the crisis in most states, March April time frame.