Covid-19 #24: You Scream, I Scream, We all Scream for Vaccine

[Zorral]

3 hours ago, Wilbur said:

Chinese authorities are now indicating that anal swabs are the superior testing method compared to saliva or nasal swabs, and they are using it in Beijing and other major metro areas.

Is this related to why testing sewage water discharge is a method by which to tell how prevalent covid-19 is in a city?

[The Anti-Targ]

8 minutes ago, Zorral said:

Is this related to why testing sewage water discharge is a method by which to tell how prevalent covid-19 is in a city?

My question is, since coughing and sneezing can aerosolise the virus and facilitate spread, hence masks help to reduce transmission, does the same apply to flatulence? Should people be wearing butt masks? Is it time to start buying shares in adult diaper companies and / or panic buying them?

[Impmk2]

29 minutes ago, Mudguard said:

I think the half-life in minutes for mRNA that you are referring to is the half life in cells.  In the vaccine preparation, it should be much longer.  The Pfizer mRNA vaccine can be stored in the fridge for up to 5 days.

Scale up is one of the big issues for both types of vaccines.  Also, production of drugs/vaccines for human use is much more stringent than product of materials for research use.  There are likely many testing and validation steps throughout the manufacturing process.  So depending on how large the lot size is, I could see it taking about a month to manufacture.

I believe the mRNA vaccines are made through a synthetic process.  Synthesizing enough mRNA, which uses modified nucleosides, for a millions doses requires extremely specialized manufacturing processes that will take time to scale up.  And for both types of vaccines, they are relying on third party suppliers for many raw materials, such as the modified nucleosides for the mRNA vaccine, and cell culture media for adenovirus vaccines.  How fast their suppliers can ramp up production will affect how fast Pfizer, Moderna, and Astrazeneca can scale up their own processes.  It's not all in their control.  Kind of like how shortage of basic reagents were holding up coronavirus testing early on.  I assume similar supply chain problems are occurring with the unprecedented amount of vaccine production that is going on right now.  People shouldn't be surprised about 3 to 6 month delays as these issues are worked out.

I'm not sure about the half-life in their manufacturing process. Naked mRNA degrades pretty quickly at 4C outside of the cell too, as anyone who has done any degree of RT-PCR can attest to, you certainly can't get comparable results if you leave things lying around. I'm sure there's way to stabilize the mRNA during synthesis, but I doubt that takes a month, and once produced it's encapsulated in a lipid nanoparticle which should stabilize it. But I was largely being pedantic and pushing back against having a large bioreactor type deal producing monthly batches - the mRNA would degrade and it seemed to suggest confusion with viral production which more typically operates more like that.

I can very much believe production issues are around ramping up scale in the synthesis process, and supply or raw materials.

 

[williamjm]

I thought this was interesting and encouraging even if there are some caveats about it being early data: https://www.nytimes.com/2021/01/25/world/middleeast/israels-vaccine-data.html
 

Quote

 

Israel, which leads the world in vaccinating its population against the coronavirus, has produced some encouraging news: Early results show a significant drop in infection after just one shot of a two-dose vaccine, and better than expected results after both doses.

Public health experts caution that the data, based on the Pfizer-BioNTech vaccine, is preliminary and has not been subjected to clinical trials. Even so, Dr. Anat Ekka Zohar, vice president of Maccabi Health Services, one of the Israeli health maintenance organizations that released the data, called it “very encouraging.”

 

Also this bit is relevant to some of our previous discussions:

Quote

 

A hazard of releasing raw data, experts cautioned, is that it can be misinterpreted.

        After Clalit first publicized its early numbers two weeks ago, many people heard about a 33 percent drop in cases, not the expected 95 percent, and jumped to the erroneous conclusion that the Pfizer shot didn’t work.

        There was an uproar in Britain, where the authorities have delayed giving the second dose by up to 12 weeks, as opposed to the 21-day gap on which Pfizer based its trials.

        Professor Balicer thought of the results as good news and was dismayed at how they were interpreted.

        “We were reassured enough to tell everyone that we were seeing what we were supposed to be seeing right after Day 14,” he said. “I don’t know how it turned into a message of ‘Oh my God, it doesn’t work.’”

 

I think it is a real problem that data is often misinterpreted and if it is bad news it will get spread faster than any later correction will. Overall I don't think the media have done a particularly good job of covering the science through the pandemic, perhaps because a lot of the journalists don't really understand it.

 

[Mudguard]

Thinking about the mRNA vaccines a little more, I do have some concerns that a variant cocktail version won't be feasible due to adverse side effects.  Seems pretty common that people develop fevers to the shot, so upping the dosage by a factor of 2 or 3 might not be feasible unless they determine that they can cut the dose for each variant by a factor of 2 or 3 so that the total vaccine is the same.  Maybe the shots would have to be given separately if the side effects are not tolerable in the cocktail version.

Also, I don't think we know what the long term efficacy of giving a lipid nanoparticle type vaccine will be yet.  It's possible that you could develop antibodies to one or more of the lipids that form the lipid nanoparticles that could reduce the efficacy of the vaccine.  Maybe the large dose they give you overcomes this, but it's something that needs to be watched.  It's possible that if you are given an mRNA vaccine packaged in lipid nanoparticles they will be less effective the following year after you've developed strong neutralizing antibodies to the lipid.  

It's good that we have dozens of other types of vaccines in development.  We may end up needing to use them all in the coming years.

[Zorral]

33 minutes ago, The Anti-Targ said:

My question is, since coughing and sneezing can aerosolise the virus and facilitate spread, hence masks help to reduce transmission, does the same apply to flatulence? Should people be wearing butt masks? Is it time to start buying shares in adult diaper companies and / or panic buying them?

If you're the sort that runs about butt naked, thinking it's as cool and edgy and smart as NOT wearing a mask, go for it.

~~~~~~~~

[paywalled]

https://www.newyorker.com/science/medical-dispatch/joe-bidens-pandemic-plan-might-actually-work

Quote

 

....The Biden plan is bold and comprehensive; it includes many of the measures that public-health experts have been advocating for months. Much of it—invoking the D.P.A., mobilizing federal resources, erecting emergency vaccination centers, establishing clear guidance on vaccine distribution and eligibility—can be accomplished through executive action or the bully pulpit. But other parts, such as funding public-health workers and supercharging vaccine administration, will require support from Congress and coöperation from states. In any event, Wen told me, an effective vaccination campaign will get us only so far. “Vaccines are not going to get us out of the immediate surge,” she said. “The Biden team needs to set the right expectations. Otherwise, people will say, ‘We’re vaccinating all these people. Why are cases still going up?’ The public deserves clear communication about what vaccines can achieve and when they can achieve it.” She went on, “The immediate trajectory of the pandemic really depends on people’s behavior. It’s unrealistic to expect that, when Biden starts to talk about physical distancing, it will suddenly convince everyone in the country to act differently.”

The need for distancing has never been greater. America’s vaccination effort is unfolding against the backdrop of a vast viral surge. In December, the U.S. recorded more coronavirus infections, hospitalizations, and deaths than in any prior month. Health-care systems are only now beginning to contend with new cases resulting from Christmas and New Year’s get-togethers. Even in optimistic scenarios—assuming Biden makes good on his pledge and then some—the vaccines will come too late for too many: the brutal reality is that, in all likelihood, another hundred and fifty thousand Americans will die of covid-19 in the first hundred days of his Presidency. “The essence of the problem is that, on the one hand, with the vaccines, we have more rationale for hope than we’ve ever had,” Frieden said. “On the other hand, we have to double-down on protection protocols.” Epidemiological modelling from prior epidemics suggests that, perversely, optimism about the end of an outbreak can lead to its persistence; the knowledge that the vaccines are effective may seem to license risky behavior that will spread the disease.

Distancing, tracing, isolating: these “non-pharmaceutical interventions” fall within the realm of public health. Under the Trump Administration, the United States went without a national, coördinated public-health response. States have had to bid against one another for critical supplies; testing and contact tracing remain inadequate, and public-health agencies are sidelined. The lack of federal support has been incomprehensible and deadly. Now, as new and more contagious strains of the coronavirus emerge, it’s also becoming clear that the country has no surveillance system to track genetic variants. We’re flying blind—unable to detect, much less extinguish, the coronavirus mutants that threaten to upend the depressing equilibrium we’ve accepted to date....

 

 

[The Anti-Targ]

13 minutes ago, williamjm said:

I thought this was interesting and encouraging even if there are some caveats about it being early data: https://www.nytimes.com/2021/01/25/world/middleeast/israels-vaccine-data.html
 

Also this bit is relevant to some of our previous discussions:

I think it is a real problem that data is often misinterpreted and if it is bad news it will get spread faster than any later correction will. Overall I don't think the media have done a particularly good job of covering the science through the pandemic, perhaps because a lot of the journalists don't really understand it.

 

I think that's being rather charitable in some cases. Some journalists will be actively opposed to what the science is telling us, including perpetuating such things as, no worse than the flu, not a real disease, and Jewish / Bill Gates conspiracy.

[Fragile Bird]

I wasn't going to post this video because I thought people would find it too simplistic, but I did find the basic explanation of making an mRNA vaccine helpful.

Especially once people start talking about nanoparticles.

https://www.youtube.com/watch?v=7hdlogIKAq4

[williamjm]

9 minutes ago, The Anti-Targ said:

I think that's being rather charitable in some cases. Some journalists will be actively opposed to what the science is telling us, including perpetuating such things as, no worse than the flu, not a real disease, and Jewish / Bill Gates conspiracy.

There are certainly those as well (and they're an even bigger problem), but I was also thinking of some of the stories I've seen in the likes of The Guardian which have sometimes been really poorly written even if they don't have an anti-vaccine agenda.

[Mudguard]

17 minutes ago, Fragile Bird said:

I wasn't going to post this video because I thought people would find it too simplistic, but I did find the basic explanation of making an mRNA vaccine helpful.

Especially once people start talking about nanoparticles.

https://www.youtube.com/watch?v=7hdlogIKAq4

Looks like a good basic summary of the process.  I wasn't sure how the mRNA was made, whether it was grown in cells or synthesized using a chemical process that is commonly used to generate oligonucleotides.  Did some digging and it looks like the video is roughly accurate for the mRNA vaccines.  The mRNA is over 4000 bases long, which is probably too large to efficiently do using a purely synthetic method, so instead it is grown in E. Coli in the form of DNA plasmids, which are are much more stable than mRNA and are later converted to mRNA.

From the wiki on the Pfizer-BioNTech vaccine, which links to a Washington Post article I don't have access to:

Quote

Pfizer is manufacturing the vaccine in its own facilities in a three-stage process. The first stage, conducted at a small pilot plant in St. Louis, involves the molecular cloning of DNA plasmids that code for the spike protein by infusing them into Escherichia coli bacteria. After four days of growth, the bacteria are killed and broken open, and the contents of their cells are purified over a week and a half to recover the desired DNA product. The DNA is stored in tiny bottles and frozen for shipment. Safely and quickly transporting the DNA at this stage is so important that Pfizer has used its company jet and helicopter to assist.^[104]

The second stage is being conducted at plants in Andover, Massachusetts in the United States, and in Germany. The DNA is used as a template to build the desired mRNA strands. Once the mRNA has been created and purified, it is frozen in plastic bags about the size of a large shopping bag, of which each can hold up to 5 to 10 million doses. The bags are placed on special racks on trucks which take them to the next plant.^[104]

The third stage is being conducted at plants in Kalamazoo, Michigan in the United States, and Puurs in Belgium. This stage involves combining the mRNA with lipid nanoparticles, then filling vials, boxing vials, and freezing them.^[104] Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids.^[105] As of November 2020, the major bottleneck in the manufacturing process was combining mRNA with lipid nanoparticles.^[104]

Step 1 takes 2 weeks, and with all the steps taking place in different areas, I could see it taking about another 2 weeks, so a month in total for the whole process.  10 large shopping bags worth of mRNA holds about 100 millions doses worth about a billion USD, or about $100 million per bag.  Pretty crazy.  Imagine if a bag of material needs to be tossed because of a problem like contamination or improper temperature during transport.  

[Fragile Bird]

So, as I said before, I watched a news report that said approximately one month to manufacture the vaccine. I think about the same amount of time is required for the Moderna vaccine.

[Impmk2]

32 minutes ago, Mudguard said:

Looks like a good basic summary of the process.  I wasn't sure how the mRNA was made, whether it was grown in cells or synthesized using a chemical process that is commonly used to generate oligonucleotides.  Did some digging and it looks like the video is roughly accurate for the mRNA vaccines.  The mRNA is over 4000 bases long, which is probably too large to efficiently do using a purely synthetic method, so instead it is grown in E. Coli in the form of DNA plasmids, which are are much more stable than mRNA and are later converted to mRNA.

From the wiki on the Pfizer-BioNTech vaccine, which links to a Washington Post article I don't have access to:

Step 1 takes 2 weeks, and with all the steps taking place in different areas, I could see it taking about another 2 weeks, so a month in total for the whole process.  10 large shopping bags worth of mRNA holds about 100 millions doses worth about a billion USD, or about $100 million per bag.  Pretty crazy.  Imagine if a bag of material needs to be tossed because of a problem like contamination or improper temperature during transport.  

That process seems crazy. I never would've guessed it'd take that long to purify the plasmid. Small scale that's literally a 15 minute job, though I imagine their quality requirements are much higher.

Seems like there'd be a lot of room for increased efficiency by just consolidating the manufacturing process to a single site. But who knows how viable that'd be.

ETA: I guess the 3 sites explains why they're operating on such a large batch basis, rather than the more continuous work flow that the nature of the vaccine would suggest.

[Padraig]

The New York Times article on Israel is very interesting.  The results across 2 doses seem excellent so far. 

I have a question about the 1 dose strategy though.  Do you get some immunity after 1 dose but it quickly dies off (e.g. 6 to 12 weeks)? 

Or do you get some immunity after 1 dose (and it should stick around for at least 6 months but maybe way more) and you need a second dose to increase the immunity even more (e.g. up from 60% to 95%?).  But the length of time that your immunity survives doesn't change too much.

I had assumed the former but I realised I could be wrong.

[Fragile Bird]

CNN is doing a Town Hall right now on Covid-19, with Andersen Cooper, Dr. Gupta, Dr. Fauci and the woman who's name I can't remember, the new head of the CDC. Dr. Fauci says they are already working on a booster for the South African strain.

[The Anti-Targ]

1 hour ago, Padraig said:

The New York Times article on Israel is very interesting.  The results across 2 doses seem excellent so far. 

I have a question about the 1 dose strategy though.  Do you get some immunity after 1 dose but it quickly dies off (e.g. 6 to 12 weeks)? 

Or do you get some immunity after 1 dose (and it should stick around for at least 6 months but maybe way more) and you need a second dose to increase the immunity even more (e.g. up from 60% to 95%?).  But the length of time that your immunity survives doesn't change too much.

I had assumed the former but I realised I could be wrong.

There could be different reasons for needing more than one shot.

It's possible that after 1 dose X% of people develop a strong immune response and they don't really need a second dose, but X is not really enough to reach good population immunity levels and what you need is X+Y to get good population immunity. And it so happens that a second dose of vaccine gives you Y. X+Y doesn't necessarily need to = 100% for effective population immunity. If X>>>Y then with a limited capacity to administer the vaccine (a combination of supply and facilities / personnel to do the job) getting a high number of people their first dose can provide better population level immunity than giving half that number of people 2 doses.

But for other vaccines you might get 100% of people developing a weak immune response from 1 dose, but it is not enough to prevent disease / infectiousness, and probably the also immunity wanes after not too long. But a second dose within a short period will give you a strong immune response that will prevent disease and prevent infectiousness as well as lasting for long enough to get population level immunity.

I am assuming that for the mRNA vaccines the quoted % for immune response after 1 dose is the former situation, because this makes sense with a 1-dose strategy. If the mRNA vaccines immune response aligns with the latter then a 1 dose strategy is not going to achieve much. If the 1 dose strategy was based on advice from immunology experts with a good understanding of the mRNA vaccine functionality then I would be confident that a proportion of recipients will develop good immunity after 1 dose and would not really need a second dose. But as there is no cheap and quick way to find out who develops good immunity after 1 dose, under normal conditions everyone needs to get a second dose, despite it being technically a waste of vaccine for a majority of people.

[A True Kaniggit]

1 hour ago, Fragile Bird said:

CNN is doing a Town Hall right now on Covid-19, with Andersen Cooper, Dr. Gupta, Dr. Fauci and the woman who's name I can't remember, the new head of the CDC. Dr. Fauci says they are already working on a booster for the South African strain.

Oooooh. I see how it is. You know the men’s names, but not the woman’s. Sexist .

[Fragile Bird]

54 minutes ago, A True Kaniggit said:

Oooooh. I see how it is. You know the men’s names, but not the woman’s. Sexist .

I know, I know! Terrible, isn't it? I've seen her a few times and the name doesn't stick n my head, but I've seen Cooper and Gupta for years and Fauci for a year. Rochelle Walensky is her name. Now that I've typed it once, I should be able to remember it. Dr. Rochelle Walensky.

Did you know her name?

[A True Kaniggit]

1 minute ago, Fragile Bird said:

I know, I know! Terrible, isn't it? I've seen her a few times and the name doesn't stick n my head, but I've seen Cooper and Gupta for years and Fauci for a year. Rochelle Walensky is her name. Now that I've typed it once, I should be able to remember it. Dr. Rochelle Walensky.

Did you know her name?

Negative. Didn’t know her until you brought her up.

[A True Kaniggit]

56 minutes ago, Fragile Bird said:

I know, I know! Terrible, isn't it? I've seen her a few times and the name doesn't stick n my head, but I've seen Cooper and Gupta for years and Fauci for a year. Rochelle Walensky is her name. Now that I've typed it once, I should be able to remember it. Dr. Rochelle Walensky.

Did you know her name?

On an aside. We seem to memorize things the same way. Kudos! 

(Rochelle Walensky is her name. What is her name? Rochelle Walensky. The name of the person I’m trying to remember is Rochelle Walensky)

[Gorn]

9 hours ago, The Anti-Targ said:

My question is, since coughing and sneezing can aerosolise the virus and facilitate spread, hence masks help to reduce transmission, does the same apply to flatulence? Should people be wearing butt masks?

They already do. I believe the technical term is "underwear".