COVID-19 Vaccine Progress: Are We Ready for Rollout in Australia?

[Borg]

I have seen news reports that the vaccine will be free for everyone but you could still get charged an "administrative fee" by your insurance company.

 

[bhobba]

UQ Vaccine Dead In The Water - And For A Very Surprising Reason

The vaccine works fine, is perfectly safe, excellent protection, and everything was on track. The problem that emerged had nothing to do with what the vaccine was being used for - it was - get this - the molecular clamp used was from the HIV virus. No chance of getting HIV - but people got a large number of false positives on HIV tests. With a large number of people getting the vaccine it will make HIV tests useless:
https://www.ndtv.com/world-news/aus...-trials-due-to-hiv-antibody-positives-2337285

They could have used many other virus fragments as the clamp, it's just they chose HIV - the wonders of scientific research. I bet hardly anybody saw this one coming. The team developing it saw it as a very remote possibility - I guess their judgement was 'a bit' off.

Thanks
Bill

 

[bhobba]

I have seen news reports that the vaccine will be free for everyone but you could still get charged an "administrative fee" by your insurance company.

That is surprising. Here in Aus it is freely supplied by the government for anyone that wants it, subject to supply. We got 10 million doses of the Pfizer vaccine being rolled out in the UK. Since we now have it well under control the government has decided to wait until the UK rollout is well underway before using the Pfizer vaccine - expected in about a month or two's time. But of the 25 million in Australia this is only enough for 5 million people so will be rationed. CSL are currently manufacturing 58 million doses of the Oxford vaccine in Melbourne ready to start rollout in January if approved - but again we may wait until using it. It is enough with 2 doses for each person for Australia, NZ, and PNG (taking into account the Pfizer vaccine we have 10 million doses of). But with the discovery that a half dose initially of the Oxford vaccine may give better results, potentially we can supply it to more countries in the South Pacific region. That is the first batch. They were then supposed to do a similar number of doses of the UQ vaccine, but that is now off the table - what CSL does then is now up for grabs - but it is expected to manufacture 50 million doses of the Novavax vaccine.

Thanks
Bill

 

[kyphysics]

Covid-19: F.D.A. Clears Pfizer Vaccine and Millions of Doses Will Be Shipped Right Away
https://www.nytimes.com/live/2020/12/11/world/covid-19-coronavirus

The accelerated timeline comes after President Trump’s chief of staff threatened the F.D.A. head’s job if he didn’t get it done on Friday. The Trump Administration will buy another 100 million doses of Moderna vaccine.

The Food and Drug Administration authorized Pfizer’s Covid-19 vaccine for emergency use on Friday, clearing the way for millions of highly vulnerable people to begin receiving the vaccine within days.

Pfizer has a deal with the U.S. government to supply 100 million doses of the vaccine by next March. Under that agreement, the shots will be free to the public.

Is anyone's state/city announcing vaccination sites/protocols yet? I've only heard that we will have some for medical workers this month. They are first in line, along with nursing home residents.

Here's a question:
US Population: ~330 million
US Positively Tested COVID cases: 16 million
Possible Real US COVID count (conservative 5x): 80 million
Possible Real US COVID count (moderate 10x): 160 million
Possible Real US COVID count (higher end 20x): 320 million

I've seen scientists offer a range from between 5x to 20x (depending on that particular person) the official case positivity rate as the likely "real infection rate," as we know many who are asymptomatic never get tested. Some estimate for every positively tested case, there are 5x as many who have it and don't go in for testing. I've seen one article go has high as 20x as a possibility. That seems unlikely to me, given the U.S. population is 330 million, a 20x figure would make the real case count 320 million, and yet we're still seeing a massive surge. I'd think if 320 million had it already, there'd be lots of immunity already and less of a surge.

Anyhow, if the US will have 100 million doses by March and we get mass vaccination done with that, how long do you think it'd take before we had a situation of de facto herd immunity (from a combination of people who've already had COVID and those taking the vaccine)?

Using 80 million from the 5x multiplier + 100 million vaccine doses, we get 180 million. However, there's no guarantee you won't have an overlap of people who've already had COVID and never got tested and those who get a vaccine shot. Obviously, there will be some overlap, so you won't get the full 180 million immune individuals. Nonetheless, any thoughts on how fast we could get some sort of herd immunity?

That is surprising. Here in Aus it is freely supplied by the government for anyone that wants it, subject to supply. We got 10 million doses of the Pfizer vaccine being rolled out in the UK. Since we now have it well under control the government has decided to wait until the UK rollout is well underway before using the Pfizer vaccine - expected in about a month or two's time. But of the 25 million in Australia this is only enough for 5 million people so will be rationed.

I'm not surprised. They love to pass costs down to the average person here in the U.S. I'm glad the vaccine is free and hope the fee is less than $200.

I might actually prefer to be in Australia's situation vs. U.S. You guys had 28 days of no cases until very recently (mentally/emotionally, I think that'd feel amazing). In the U.S., we've had 28+ days of 100,000 or more (recently many 200,000 case days) cases. Sort of the exact opposite. Only good thing is we're getting that 100 million doses.

 

[bhobba]

I might actually prefer to be in Australia's situation vs. U.S. You guys had 28 days of no cases until very recently (mentally/emotionally, I think that'd feel amazing). In the U.S., we've had 28+ days of 100,000 or more (recently many 200,000 case days) cases. Sort of the exact opposite. Only good thing is we're getting that 100 million doses.

Yes we have had recently a slight uptick. But fortunately it is mostly in people already quarantined from overseas. This is only to be expected as the government tries to clear the backlog of Australians trying to get back into Australia.

That why we can afford to wait a bit until 'unleashing' the vaccine - we can evaluate the results in other countries first. The US and UK IMHO has no other choice - vaccinate immediately - it seems to be the only chance of bringing it under control in those countries.

Thanks
Bill

 

[Ivan Seeking]

I am not clear on the meaning of herd immunity if the spike protein antibodies do not provide general immunity. If you are immune to infection but can still be a carrier and spread the disease, does the concept of herd immunity even apply?

If we find that the Pfizer vaccine does prevent spread, great. But we don't know yet and they keep talking about herd immunity as if it's a given [assuming enough people get vaccinated, which is another issue]. This seems inconsistent to me.

 

[Ivan Seeking]

I am not clear on the meaning of herd immunity if the spike protein antibodies do not provide general immunity. If you are immune to infection but can still be a carrier and spread the disease, does the concept of herd immunity even apply?

If we find that the Pfizer vaccine does prevent spread, great. But we don't know yet and they keep talking about herd immunity as if it's a given [assuming enough people get vaccinated, which is another issue]. This seems inconsistent to me.

What is herd immunity?
When most of a population is immune to an infectious disease, this provides indirect protection—or herd immunity (also called herd protection)—to those who are not immune to the disease.

For example, if 80% of a population is immune to a virus, four out of every five people who encounter someone with the disease won’t get sick (and won’t spread the disease any further). In this way, the spread of infectious diseases is kept under control. Depending how contagious an infection is, usually 50% to 90% of a population needs immunity to achieve herd immunity.

https://www.jhsph.edu/covid-19/articles/achieving-herd-immunity-with-covid19.html

Note the qualifier which was actually in parentheses and then highlighted by me. By this definition, the concept of herd immunity has no meaning for vaccines that don't prevent spread.

 

[bhobba]

But we don't know yet and they keep talking about herd immunity as if it's a given [assuming enough people get vaccinated, which is another issue]. This seems inconsistent to me.

I think the standard of reporters has dropped alarmingly. Yes it is inconsistent. We will not know about herd immunity until we know more about the vaccines.

I was going to do a separate post about this, but IMHO, the rot that is floating around about Covid and vaccines is alarming. Here is a little ditty I came across on youtube:



I gave a reply I will repeat here for convenience:

There is no cover up. This is old news. It is called the Covax-19 vaccine. Stage 1 trials happened in late June:
https://www.eurekalert.org/pub_releases/2020-07/fu-ato070320.php.

It passed with flying colours and Professor Petrovsky, in August proposed using it immediately:
https://www.news.com.au/world/coronavirus/australia/promising-south-australian-vaccine-could-be-ready-in-three-or-four-months/news-story/42cbf1c4e7a5d11f2b7cb8aa186ff994

He did appear on some of the shows mentioned like Credlin etc about it, they did not ignore him, but still gained no government traction. I rang my local member about it, who is also a doctor, but still no support. The reason was the government, wrongly, pinned its hopes on the UQ Vaccine:


So the story is basically one of half truths. Yes it is a more usual vaccine with less unknowns. The reason it is not here now is the Australian government made bad mistakes in what vaccine to back - the one it backed, the UQ vaccine, turned out to have a problem with HIV tests. It was foreseeable - but they underestimated the risk. It remains to be seen if the government has learned their lesson and will now back this vaccine. But the situation is now different - we have a number of vaccines to choose from. And the government is NOT trying to kill us. They are simply incompetent and after the fact politically cover their bum. The Oxford Vaccine was subjected to double blind trials (so much for the claim no vaccine has been subjected to double blind trials) and issues were found that needed to be investigated before proceeding:
https://theconversation.com/the-oxford-vaccine-trial-has-been-paused-but-this-is-no-reason-to-panic-145882

It all was sorted out - in fact the control group that didn't get the vaccine had more 'adverse reactions' - interesting isn't it. The Oxford vaccine is safe - how effective it is, is another matter that is still being investigated. Of course safe is up to the 30,000 or so in the stage 3 trials - as it is with any new vaccine. It must be slowly rolled out to establish safety in a larger population and that is why here in Aus we are waiting for other countries to use it first.

It is such obvious rot - yet people believe it - even believe there is no virus. I had a long argument with someone about that - even sending him the genomic sequence. It made no difference. We are living in 'crazy' times.

Thanks
Bill

 

[Ivan Seeking]

I think the standard of reporters has dropped alarmingly. Yes it is inconsistent. We will not know about herd immunity until we know more about the vaccines.

Can't blame reporters. I have seen this in a number of interviews with experts, the most recent being
William Schaffner, who is an infectious disease expert from Vanderbilt.

 

[Ivan Seeking]

Nobody discusses what the Covid world looks like if mRNA vaccines don't prevent spread.

Another big problem is that of testing additional vaccines. Is it ethical to give a test subject a placebo when we have an effective vaccine?

 

[bhobba]

Nobody discusses what the Covid world looks like if mRNA vaccines don't prevent spread. Another big problem is that of testing additional vaccines. Is it ethical to give a test subject a placebo when we have an effective vaccine?

That is a very interesting question.

One of our national heroes here in Aus, Professor Borody (discoverer of the cure for Peptic Ulcers) has a rather interesting take on it:
https://covexit.com/professor-thomas-borody-interview-part-2/

Personally I think once we have a vaccine that works, further vaccines need to be investigated by Challenge Trials, which seems to be what the UK is doing:
https://www.nature.com/articles/d41586-020-02821-4

We already have a significant number of volunteers:
https://www.1daysooner.org/

Just my view of course. But then again I am gung ho about a lot of things others are more cautious about such as Ivermectin, use of the Covax-19 vaccine earlier etc. This pandemic is simply terrible - we need some 'true grit'.

Thanks
Bill

 

[berkeman]

Another big problem is that of testing additional vaccines. Is it ethical to give a test subject a placebo when we have an effective vaccine?

See the discussion about this in this other thread:

https://www.physicsforums.com/threa...th-two-different-vaccines.996437/post-6422445

 

[Ygggdrasil]

Nobody discusses what the Covid world looks like if mRNA vaccines don't prevent spread.

Here's a good piece from STAT news on the various future prospects for immunity to COVID-19:
https://www.statnews.com/2020/08/25/four-scenarios-on-how-we-might-develop-immunity-to-covid-19/

The most likely scenario is that once people are either exposed to the virus or are immunized, people could still be re-infected by the virus (allowing the virus to keep circulating in human populations), but the immunity will lessen the severity of the disease such that it joins the ranks of the four other endogenous human coronaviruses that cause only mild colds:

Under this scenario, people whose immune systems have been primed to recognize and fight the virus — whether through infection or vaccination — could contract it again in the future. But these infections would be cut short as the immune system’s defenses kick into gear. People infected might not develop symptoms or might have a mild, cold-like infection.

Another big problem is that of testing additional vaccines. Is it ethical to give a test subject a placebo when we have an effective vaccine?

The journal Science published a piece discussing this subject (also linked to in the thread that @berkeman cited): https://science.sciencemag.org/content/370/6522/1277.full

 

[Buzz Bloom]

Another big problem is that of testing additional vaccines. Is it ethical to give a test subject a placebo when we have an effective vaccine?

I recall reading somewhere about a protocol in which a placebo is NOT used, and instead an existing medication or vaccine is used. The intent is to determine which is better, the old or the new, or whether there are individual patient characteristics that make one more effective than the other for people with such characteristics. For example, a person with high blood pressure might benefit more from A than B, while person with normal blood presure would benefit more from B.

It may be that since at the present time there is no currently av ailable effective vaccine, this protocol has not been discussed.

 

[Ygggdrasil]

I recall reading somewhere about a protocol in which a placebo is NOT used, and instead an existing medication or vaccine is used. The intent is to determine which is better, the old or the new, or whether there are individual patient characteristics that make one more effective than the other for people with such characteristics. For example, a person with high blood pressure might benefit more from A than B, while person with normal blood presure would benefit more from B.

It may be that since at the present time there is no currently av ailable effective vaccine, this protocol has not been discussed.

Such a trial design is called a "non-inferiority" trial, which aims to test whether the candidate vaccine provides measurably less protection than the control vaccine. Such trials, however, are difficult to run and could require larger and/or longer trials than placebo-controlled trials.

“If the availability of a COVID-19 vaccine proven to be safe and effective precludes ethical inclusion of a placebo control group, that vaccine could serve as the control treatment in a study designed to evaluate efficacy with non-inferiority hypothesis testing.”

It is far from clear, however, that non-inferiority trials of COVID-19 vaccines would be feasible. Moreover, the difficulty of doing this could preface pressure on FDA to accept external control arms or real-world data as controls.

Demonstrating non-inferiority to an effective intervention can require very large trials or the acceptance of large confidence intervals around the results. The placebo-controlled Phase III COVID-19 trials already include at least 30,000 participants, and there will be little acceptance of uncertainty about the efficacy of a vaccine to prevent a life-threatening disease.

https://www.biocentury.com/article/631294

Challenge trials (such as ones proposed in the UK) could be a means to more quickly compare efficacy of vaccines than a non-inferiority trial to determine which should be given EUAs, and then researchers could design longer-term post-approval monitoring studies to compare the safety outcomes of the various vaccines to identify any that could be associated with higher risks of adverse events.

 

[russ_watters]

Is anyone's state/city announcing vaccination sites/protocols yet? I've only heard that we will have some for medical workers this month. They are first in line, along with nursing home residents.

Here's a question:
US Population: ~330 million
US Positively Tested COVID cases: 16 million
Possible Real US COVID count (conservative 5x): 80 million
Possible Real US COVID count (moderate 10x): 160 million
...

However, there's no guarantee you won't have an overlap of people who've already had COVID and never got tested and those who get a vaccine shot. Obviously, there will be some overlap, so you won't get the full 180 million immune individuals. Nonetheless, any thoughts on how fast we could get some sort of herd immunity?

I have a question here that you may have been thinking but didn't really ask: has there been any thought toward antibody or infection testing people prior to vaccinating them? I haven't seen anything, so my guess is no. I don't understand why they wouldn't do that, as vaccinating everyone would seem to waste a significant fraction of the available vaccines and substantially delay reaching the herd immunity threshold.

Similarly, I haven't heard discussion of the COVID endgame, which might warrant its own thread. How, exactly, does the vaccine provide a path to ending the outbreak and re-opening societies? Again, I'm seeing nothing, so I'm speculating that there is no plan and re-opening will simply happen when governments think there has been enough of a drop in infection rates. But that seems unwise from both directions: a business could re-open earlier to people who are likely to be immune or if businesses open to everyone too early, more people may become infected.

The "successful" countries are most at risk in the endgame, both healthwise and economically. Does New Zealand remain on travel lockdown until everyone in the country is vaccinated?

 

[russ_watters]

I am not clear on the meaning of herd immunity if the spike protein antibodies do not provide general immunity. If you are immune to infection but can still be a carrier and spread the disease, does the concept of herd immunity even apply?

I haven't heard of that - do you have a source where you heard it? It doesn't make sense to me; if a person is immune, that means their body isn't mass-producing the virus, doesn't it? Is there any evidence that people can be long-term asymptomatic carriers?

 

[kyphysics]

I have a question here that you may have been thinking but didn't really ask: has there been any thought toward antibody or infection testing people prior to vaccinating them? I haven't seen anything, so my guess is no. I don't understand why they wouldn't do that, as vaccinating everyone would seem to waste a significant fraction of the available vaccines and substantially delay reaching the herd immunity threshold.

No, I hadn't thought of that question, but it's a fair one.

I guess I'd previously read so many articles on seeming unreliability of antibody tests in the past that I subconsciously thought it might not be the best route. I figured they'd still go with the most vulnerable first on down to the healthiest and least likely to get sick. As in, why risk a false negative test and not vaccinate someone who is vulnerable and may actually need it?

I haven't kept up with the science on this, so have they found more reliable tests for immunity yet? Wondering what the false negative rate may be? If very low, then maybe it would be worth using them in the vaccination decision making process (at least with less vulnerable people).

 

[Ygggdrasil]

I haven't heard of that - do you have a source where you heard it? It doesn't make sense to me; if a person is immune, that means their body isn't mass-producing the virus, doesn't it? Is there any evidence that people can be long-term asymptomatic carriers?

Here's a good piece discussing some of the possible prospects for immunity against SARS-CoV-2: https://www.statnews.com/2020/08/25/four-scenarios-on-how-we-might-develop-immunity-to-covid-19/

I'll quote the relevant piece on evidence against why we might not expect a vaccine to prevent transmission of the virus (though the full piece is worth a read):

Diseases that we think of as “one-and-done” infections induce such a robust and durable immune response in a single encounter that we cannot be reinfected. In general terms, measles fits into this category, although there are rare reports of people contracting measles more than once.

The bad news is that viruses that infect via the mucus membranes of the nose and throat, like SARS-2, typically don’t induce sterilizing immunity.

“Sterilizing [immunity] in my view is out of the question, as with any respiratory virus,” said Marion Koopmans, head of virology at Erasmus Medical Center in Rotterdam, the Netherlands. Stanley Perlman, a Coronavirus researcher at the University of Iowa, called this option “not so likely.”

But Florian Krammer, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai Hospital in New York, does believe some people will develop sterilizing immunity after a bout of Covid-19.

One last observation about sterilizing immunity: If infection doesn’t trigger it, there is reason to be concerned that vaccines may not either. Peiris noted that so far most of the experimental vaccines, when tested in primates, protect the lungs from severe disease but don’t block replication of virus in the upper airways.

If the primates predict how the vaccines will work in people, these studies would suggest that people may still be able to be infected and they may emit viruses that potentially could infect others, but the type of Covid-19 disease that lands people in ICUs and that sometimes kills them would be prevented.

 

[russ_watters]

Thanks.

Totally separate issue/question: Why isn't every able pharma company on the planet now manufacturing the Pfizer or Moderna vaccine?

 

[Ygggdrasil]

Thanks.

Totally separate issue/question: Why isn't every able pharma company on the planet now manufacturing the Pfizer or Moderna vaccine?

mRNA vaccines are a very new technology, so it would probably take substantial investment of time and capital for a company to put into place the proper systems for manufacturing an mRNA vaccine. Given that it was unknown whether the mRNA vaccines would actually work, it was probably a smart idea to not prep the entire world's pharma manufacturing capacity toward a vaccine that may or may not work.

Why aren't all the companies now going to make the Pfizer or Moderna vaccine now that we know it works?
1) People still need drugs for other conditions. You can't stop making insulin to start making a Coronavirus vaccine.

2) Vaccines aren't that profitable compared to other drugs, so companies would want to continue making their other products:

Another challenge for those making predictions about vaccine availability is that manufacturing capacity is a closely guarded secret, and companies are unlikely to reveal precise details even to major buyers such as the U.S. government, said Lee.

“Vaccine manufacturers hold their production capacity pretty close to their vest because it’s a point of a negotiation.” he said. Companies want to have flexibility in their contracts so they can balance production of various drugs and vaccines. “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine.”

Even during a medical emergency, companies won’t reveal this information, said Mark Capofari, who was director of global logistics at Merck from 1995 to 2007 and currently lectures on supply chain management at Penn State University. During the AIDS crisis, when Merck made a key treatment drug, Crixivan, production capacity wasn’t shared outside the company, he said.

https://www.statnews.com/2020/12/11...ps-slipping-experts-say-it-will-change-again/

3) It's still not clear whether the Pfizer and Moderna vaccines are the best or safest options. We have very limited safety data on the mRNA vaccines (remember, mRNA vaccines are a new technology that have never been used outside of clinical trials before). While the data so far suggests a good safety profile, we have seen unexpected safety issues pop up already (potential for allergic reactions to components of the vaccine). Would you bet the entire world's pharma manufacturing capacity on this one technology?

There are plenty of vaccines in development that could have potential advantages over the Pfizer and Moderna vaccines. For example, both vaccines require the vaccine to be shipped and stored frozen (-20°C for the Moderna vaccine and -70°C for the Pfizer vaccine). This poses challenges for distribution in developed nations (e.g. in rural areas of the US), not to mention developing nations. In contrast, other vaccines in development can be transported and stored at normal refrigerator temperature (4°C, like other vaccines), which would allow transport, distribution and storage using normal vaccine distribution channels. Similarly, vaccines manufactured using more conventional technologies (e.g. recombinant protein vaccines) could be more easily adapted to existing biopharma manufacturing capacity than the new mRNA vaccine technologies. I doubt that mRNA vaccines will contribute the majority of Coronavirus vaccinations worldwide.

I, for one, have high hopes for the recombinant protein vaccine being produced by Novavax. Phase I/II data for this vaccine look promising, and the https://ir.novavax.com/news-releases/news-release-details/novavax-announces-covid-19-vaccine-clinical-development-progressthat interim results from its phase III trial in the UK could be available in early Q1 2021. Analysis of early clinical data and experimental studies in animals suggests that the recombinant protein vaccines might have higher efficiency and lower side effects than the other vaccine technologies (though some recombinant protein vaccines have already reported failures).

The mRNA vaccines from Pfizer and Moderna certainly look safe and effective, and deserve emergency use authorization for distribution. However, I would not yet put all the eggs in one basket for those two vaccines.

[edited to add]:
Here's a nice outlook from a review article published in Nature on the Coronavirus vaccine candidates:

For the vaccines in clinical trials for which phase I/II data are available, we observe both an immunogenicity and a reactogenicity gradient. In terms of immunogenicity, inactivated and AdV5-based vaccines seem to rank the lowest, followed by ChAdOx1-based vaccines and mRNA vaccines, and finally adjuvanted, protein-based vaccines, which show the best performance. Reactogenicity seems to be lowest in inactivated and protein-based vaccines, followed by mRNA vaccines, with vectored vaccines having the highest rate of side effects. It is highly likely that the vaccine candidates from AstraZeneca, Moderna and Pfizer—which have progressed the furthest in clinical trials in the USA and Europe—will all show sufficient efficacy and will be licensed if they are shown to be sufficiently safe. However, it might also be the case that these vaccines will be replaced at a later date by newer candidates that show similar efficacy but have more tolerable reactogenicity profiles. In addition, it is difficult to predict how availability and production capacity will shape the global landscape of SARS-CoV-2 vaccines. Although they might not be licensed in the USA and Europe, it is very likely that AdV5-based and inactivated vaccines produced in China—as well as other vaccine candidates produced in India and elsewhere—will have a major role in satisfying the global demand for vaccines against SARS-CoV-2.

https://www.nature.com/articles/s41586-020-2798-3

 

[russ_watters]

mRNA vaccines are a very new technology, so it would probably take substantial investment of time and capital for a company to put into place the proper systems for manufacturing an mRNA vaccine...

Why aren't all the companies now going to make the Pfizer or Moderna vaccine now that we know it works?
1) People still need drugs for other conditions. You can't stop making insulin to start making a Coronavirus vaccine.

The first part is probably part of the answer I was looking for; the second part isn't what I meant. Several/many pharma companies maintain federally funded, idle vaccine factories for the explicit purpose of pandemic response. One client of my company is Sanofi Pasteur, who maintains such a facility in Pennsylvania. They make seasonal flu vaccines in addition to maintaining the empty factory. About all I know of their technology is they grow it in eggs, by the millions. I'm sure that's a more conventional vaccine technology, and I don't know how easy it would be to re-tool to the new technology -- maybe not that easy.
https://www.sanofi.us/en/about-us/our-stories/our-response-to-covid-19
https://www.statnews.com/2020/12/11...setback-in-development-of-a-covid-19-vaccine/

The rest of the answer may be an issue of business and politics, which if there is ever a time to set them aside, it's during a once-a-century pandemic.

2) Vaccines aren't that profitable compared to other drugs...

That shouldn't be a relevant issue. It is a problem the governments of the world could easily choose to make go away, when faced with the worst economic crisis since the great depression. The US could spend a trillion dollars on it ($3,000 per inoculation) and it would still be worth it.

3) It's still not clear whether the Pfizer and Moderna vaccines are the best or safest options...

Would you bet the entire world's pharma [vaccine] manufacturing capacity on this one technology?

Fair enough, but I 'd suggest that "fastest" matters a lot here too. Sanofi/GSK predict their vaccine may not be ready until the second half of 2021. I'd suggest that that's too late and if they have capacity to manufacture an inferior vaccine sooner, we should make it happen.

There are plenty of vaccines in development that could have potential advantages over the Pfizer and Moderna vaccines. For example, both vaccines require the vaccine to be shipped and stored frozen (-20°C for the Moderna vaccine and -70°C for the Pfizer vaccine). This poses challenges for distribution in developed nations (e.g. in rural areas of the US), not to mention developing nations. In contrast, other vaccines in development can be transported and stored at normal refrigerator temperature (4°C, like other vaccines), which would allow transport, distribution and storage using normal vaccine distribution channels. Similarly, vaccines manufactured using more conventional technologies (e.g. recombinant protein vaccines) could be more easily adapted to existing biopharma manufacturing capacity than the new mRNA vaccine technologies. I doubt that mRNA vaccines will contribute the majority of Coronavirus vaccinations worldwide.

Sure. What I'm suggesting here is a technology sharing and prioritization effort. I've seen no indication that such a thing is in the works, and that bothers me. Heck, if a manufacturing plant is capable of it, they could manufacture the Pfizer or Moderna vaccine while the R&D arm of a company was still working on their own vaccine.

I, for one, have high hopes for the recombinant protein vaccine being produced by Novavax. Phase I/II data for this vaccine look promising, and the https://ir.novavax.com/news-releases/news-release-details/novavax-announces-covid-19-vaccine-clinical-development-progressthat interim results from its phase III trial in the UK could be available in early Q1 2021. Analysis of early clinical data and experimental studies in animals suggests that the recombinant protein vaccines might have higher efficiency and lower side effects than the other vaccine technologies (though some recombinant protein vaccines have already reported failures).

The mRNA vaccines from Pfizer and Moderna certainly look safe and effective, and deserve emergency use authorization for distribution. However, I would not yet put all the eggs in one basket for those two vaccines.

Another technology in Q1 could be good from a timing perspective, especially if they can start manufacturing it before approval. But it's not so much as putting all the eggs (pun?) in one basket that I'm after, as it is using that basket for something else while we're waiting on the chickens.

Another such facility:
https://today.tamu.edu/2020/07/27/c...acturing-center-to-produce-covid-19-vaccines/

 

[russ_watters]

For example, both vaccines require the vaccine to be shipped and stored frozen (-20°C for the Moderna vaccine and -70°C for the Pfizer vaccine). This poses challenges for distribution in developed nations (e.g. in rural areas of the US), not to mention developing nations.

That's an interesting issue/twist, but not one that I'm particularly concerned with. The math on the transportation containers is straightforward, and what it says is that there's no real issue shipping huge quantities of the cryogenic vaccine. But they just haven't made smaller containers to distribute smaller quantities. That really doesn't bother me: for the time being and to get the most bang for our buck/limited supply, shipping thousands at a time to cities is a better deal than trying to ship dozens at a time to small, rural communities.

 

[Ygggdrasil]

Several/many pharma companies maintain federally funded, idle vaccine factories for the explicit purpose of pandemic response. One client of my company is Sanofi Pasteur, who maintains such a facility in Pennsylvania. They make seasonal flu vaccines in addition to maintaining the empty factory. About all I know of their technology is they grow it in eggs, by the millions. I'm sure that's a more conventional vaccine technology, and I don't know how easy it would be to re-tool to the new technology -- maybe not that easy.
https://www.sanofi.us/en/about-us/our-stories/our-response-to-covid-19
https://www.statnews.com/2020/12/11...setback-in-development-of-a-covid-19-vaccine/

The procedure for making mRNA vaccines is very different for traditional live attenuated vaccines or inactivated virus vaccines, which are the ones grown in eggs (in fact, mRNA vaccine production involves no eggs at all). First, DNA encoding the vaccine is mass produced in bacteria and purified, then the DNA is used in enzymatic reactions to produce mRNA, where it is then packaged into lipid nanoparticles. I don't know what would be involved in repurposed the traditional vaccine factories for the manufacture of mRNA vaccines, but the manufacture of the mRNA vaccines seems specialized enough that re-purposing the facilities would not be feasible. It's possible that other biopharma facilities could be more easily repurposed to create mRNA vaccines, but then you run into problems with displacing production of other pharmaceutical products. That said, it seems likely that mRNA vaccines would be the technology of choice for controlling future pandemics, so it would seem like a good investment for governments to build capacity for production of mRNA vaccines.

Similarly, recombinant protein vaccines would require different manufacturing facilities than mRNA vaccines or traditional vaccines. However, because recombinant protein technology is used in many other biopharma applications, there is probably more existing capacity for recombinant protein vaccine production (e.g. the TAMU facility in the article you cited).

It's worth noting that Chinese companies have created inactivated virus vaccines (the ones that would be produced in eggs) that claim to be ~86% effective (though the data comes only from a press release, and the underlying data have not been published yet). Perhaps we should be using those facilities to make the Sinopharm vaccine.

 

[Tom.G]

Is anyone's state/city announcing vaccination sites/protocols yet? I've only heard that we will have some for medical workers this month. They are first in line, along with nursing home residents.

From memory of 'a few days ago', Los Angeles published this priority list:

Medical workers
1) First responders (paramedics, fire, [police?])
2) Nursing Homes, residents and staff
3) High-risk members of the public (co-morbidities and age >65)
4) High-risk members of the public (co-morbidities)
5) High-risk members of the public (age>65)
6) General public

Items 4) and 5) may have been combined with the 'or' operator.

(further research turned up these)
Here is a link to the California Dept of Health recommended priorities:
https://www.cdph.ca.gov/Programs/CI...-Vaccine-During-Phase-1A-Recommendations.aspx

The California Governor announced:
https://calmatters.org/health/coronavirus/2020/12/california-priorities-first-covid-vaccines/
https://infogram.com/california-vaccine-priorities-1hxj48pp5qrkq2v

Cheers,
Tom

 

[Ygggdrasil]

From memory of 'a few days ago', Los Angeles published this priority list:

Medical workers
1) First responders (paramedics, fire, [police?])
2) Nursing Homes, residents and staff
3) High-risk members of the public (co-morbidities and age >65)
4) High-risk members of the public (co-morbidities)
5) High-risk members of the public (age>65)
6) General public

Items 4) and 5) may have been combined with the 'or' operator.

(further research turned up these)
Here is a link to the California Dept of Health recommended priorities:
https://www.cdph.ca.gov/Programs/CI...-Vaccine-During-Phase-1A-Recommendations.aspx

The California Governor announced:
https://calmatters.org/health/coronavirus/2020/12/california-priorities-first-covid-vaccines/
https://infogram.com/california-vaccine-priorities-1hxj48pp5qrkq2v

The US National Academies of Medicine published guidelines for allocating the Coronavirus vaccine. These are just guidelines, however, and states have the final say in which groups they decide to prioritize:

 

[kyphysics]

If there truly were a shortage, I'd personally be okay with not vaccinating prisoners themselves, but vaccinating the staff first. Maybe leave the prisoners to Phase 4?

 

[kyphysics]

If given a choice, which of the two major ones - Pfizer of Moderna - would you take?

Has there been any thought of someone taking both (if supplies are abundant and we can "afford to" at some point)?

 

[bhobba]

I recall reading somewhere about a protocol in which a placebo is NOT used, and instead an existing medication or vaccine is used.

That is the view of Professor Borody on when you should use double blind studies ie when comparing the efficacy of two different treatments. He thinks the moral issues of those that get a pacebo and hence have a greater risk are too great (remember before stage 3 it has passed stage 1 and 2 so we know it does work to some extent). But there is the reverse argument - there is a chance those getting the treatment do worse than the placebo. He is a very strong proponent of it as detailed in the video I gave before that for convenience I will repost:
https://covexit.com/professor-thomas-borody-interview-part-2/

I tend to agree, but consider the issue much more nuanced than if you push double blind studies where it is not appropriate (of course in his opinion) you need to go back to medical school (of course he is half joking - but still it shows how strongly he holds his view on the matter).

Thanks
Bill

 

[bhobba]

Totally separate issue/question: Why isn't every able pharma company on the planet now manufacturing the Pfizer or Moderna vaccine?

Because the accelerated process that does not compromise safety is to carry out large scale manufacturing in parallel with stage 3 studies. The Oxford vaccine for example is much cheaper than Pfizer and probably Modernia, but India is already manufacturing 1 billion doses in anticipation of approval. It seems to have a similar efficacy (to be conformed). So what do you do - if proven effective and safe throw out a billion doses? Besides the Pfizer vaccine has logistic issues with distribution due to how cold it must be stored at. Here in Aus we are making nearly 60 million doses of the Oxford vaccine to be deployed once stage 3 trials are completed to the satisfaction of our regulatory bodies, who also want to see how it goes overseas like in India before passing it. That is expected to be about March. The production of the vaccine is expected here in Aus to be finished end this year - early next year. Then we will manufacture a similar amount of the Novavax vaxine immediately after - it may be better - we do not know yet. Why not manufacture the Pfizer vaccine? CSL, our vaccine manufacturer, does not have the capability to make it.

Thanks
Bill

 

[Ygggdrasil]

Johnson & Johnson published data from the phase 1/2 trial of their vaccine candidate: https://www.nejm.org/doi/full/10.1056/NEJMoa2034201

The J&J vaccine is a viral vector vaccine, like the Oxford-AstraZeneca vaccine, though it uses a different viral vector than the Oxford-AstraZeneca vaccine. The vaccine would be easier to store than the mRNA vaccines (Pfizer-BioNTech and Moderna) as it can be stored at normal refrigerator temperature for up to three months. Notably, the trial is testing a one-dose versus two-dose administration of the vaccine.

In the study, participants had neutralizing antibodies, measured in a unit called a geometric mean titer, of 224 to 354, on day 29 after their first vaccine dose; those levels reached 288 to 488 by day 57. These levels could be enough to produce immunity. But there was a big benefit to giving the participants a booster dose. It doubled or tripled their levels of neutralizing antibodies. The question is whether the antibody levels induced by the first dose are indeed enough, or if there are other types of immunity spurred by the vaccine that lead to protection.

“Just because it’s higher in neutralizing response doesn’t necessarily mean it’s more efficacious,” said Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “It may be that the immune response induced by the first dose is enough and that more is not necessarily better.”

The answer to the question, of course, will come from Phase 3 clinical trial results. Said Carlos del Rio, a distinguished professor of medicine at the Emory University School of Medicine: “The proof is in the pudding.”

https://www.statnews.com/2021/01/13...r-jjs-one-dose-covid-vaccine-will-measure-up/

However, because the study is still only an early stage clinical trial, the study reports only on antibody levels and does not measure the actual efficacy of the vaccine in preventing disease. Efficacy data will await completion of phase 3 clinical trials (which are currently underway).

Unfortunately, these positive phase 1/2 data are tempered by news that production of the J&J vaccine is two months behind schedule, so even if approved soon, the vaccine may not be able to make an impact for a few more months:

Johnson & Johnson has fallen behind on production of its Covid-19 vaccine, a delay that could put it as much as two months behind schedule, a person briefed on the matter told POLITICO.

The company had originally pledged to deliver 12 million doses by the end of February, with plans to reach 100 million over the next four months.

But Johnson & Johnson has since warned officials that it could take until the end of April to catch up to its original projections, the person briefed on the matter said.

https://www.politico.com/news/2021/01/13/johnson-johnson-vaccine-production-458941

 

[stefan r]

...

Unfortunately, these positive phase 1/2 data are tempered by news that production of the J&J vaccine is two months behind schedule, so even if approved soon, the vaccine may not be able to make an impact for a few more months:

We need 8 or 16 billion vaccines. A large portion of them need to be available in places that do not have cold storage options. If immunity is temporary we need 8 (or 16) billion per year for a few years. Its not O.K. to vaccinate a few rich old people and then pretend everything is fine.

Waiting for the virus to mutate would be rash.

The pharmaceutical companies might make more money if the virus festers and we have to keep re-vaccinating every year for the rest of our lives. Eradication is much cheaper in the long run.

 

[Laroxe]

I was reading through the thread and thought there were a few issues worth highlighting, perhaps the most important being the speed of change in our knowledge base. The earlier link to an article in Nature, on Vaccines in development and published in September 2020, predated the recent explosion in information about both the vaccines and the immune response.
I'm not sure why the author found it necessary to describe traditional development pathways for vaccines as this was already widely discussed in the media and in fact many of these issues have effectively been consigned to history. Perhaps what is more important is the views expressed on the immune response, particularly to SARS-CoV2 might quickly be following them. At the moment it appears that generating a robust antibody response is not difficult, but we still don't know the levels required to achieve effective protection nor the changes that occur over time. A great deal of the emphasis in research has switched to the T cell responses which hold the promise of long term protection.
There is also a discussion about the rather strange idea of sterilising immunity, this really refers to the way in which a vaccine reduces transmission. As we have a reasonable idea about the infection risk presented by individuals at various stages of infection, preventing disease has a marked effect on the possible length of time a person might shed the virus and the amount of virus they shed. There is always the possibility of transmitting a virus to a non immune person, even if its simply by surface contamination just like its possible for an immune individual to become reinfected, there is more than the level of immunity to consider. We will only know the effect of the vaccine on transmission after some time, but it will have an effect.
In terms of vaccine development it is still possible to conduct trials particularly as so many areas still have no access to vaccines, this of course will become harder over time. However the phase 3 trials which need the highest numbers may still be possible in areas with low levels of vaccine acceptance.
We do need the vaccine trials to continue, its very unlikely that the very high levels of effectiveness reported in the early trials will stand the test of time, we don't know which ones will be best. There are also new vaccines that specifically target parts of the immune system, like tissue immunity in the nasopharynx, these may not require injections and might impact on transmissibility.
I just thought it was fascinating to see the rapid changes in the science and perhaps consider how political and social issues impact on its application. Remember a huge amount of money was invested in developing our vaccine production facilities and this is still going on, drug companies can't simply switch production.

 

[PeroK]

Its not O.K. to vaccinate a few rich old people and then pretend everything is fine.

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

 

[Jarvis323]

What evidence do you have that in the UK, for example, the vaccine is being given only to a few rich old people?

https://en.wikipedia.org/wiki/COVID-19_vaccination_programme_in_the_United_Kingdom

There have been complaints by the WHO, and other groups about vaccines being 'hoarded' by rich countries.

The People's Vaccine Alliance says nearly 70 lower-income countries will only be able to vaccinate one in 10 people.

https://www.bbc.com/news/health-55229894

At least 90% of people in 67 low income countries stand little chance of getting vaccinated against Covid-19 in 2021 because wealthy nations have reserved more than they need and developers will not share their intellectual property, says the People’s Vaccine Alliance, which includes Amnesty International, Frontline AIDS, Global Justice Now, and Oxfam.1

“Unless something changes dramatically, billions of people around the world will not receive a safe and effective vaccine for Covid-19 for years to come,” said Anna Marriott, Oxfam’s health policy manager.

Rich countries with only 14% of the world’s population have bought up 53% of the eight most promising vaccines, the alliance said, including all of the Moderna vaccine doses expected to be produced over the next year and 96% of the Pfizer-BioNTech vaccine doses.

https://www.bmj.com/content/371/bmj.m4809

WHO's director said only 25 vaccine doses have been provided in a single poor country, while over 39 million doses have been administered in nearly 50 richer nations

https://www.kare11.com/article/news...-old/507-b56e5785-b679-4512-9a31-de4071c7f408