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Are vaccines the light at the end of the tunnel?


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17 minutes ago, TeeRick said:

Oxford/AZ vaccine efficacy results just released.  This is the monkey adenovector vaccine.  One dosing protocol resulted in 90% efficacy.  That as a 1/2 dose followed by a full dose at 30 days.

 

Of interest- two full doses a month apart gave only 62% efficacy.  So what leads to these differences?  And why different from the two mRNA vaccines?  Lot's of possibilities starting with immune moderating effects of the adenovector itself.  There are human adenovector versions of this vaccine in phase 3 so we shall see soon if this was a species-related result (monkey vs human).  That has happened before with the vaccines for rotavirus.   We shall see.  It is nice that their are multiple approaches.  

 

https://www.cnbc.com/2020/11/23/oxford-astrazeneca-covid-vaccine-is-70percent-effective-trial-shows-.html

Yay AstraZeneca!!!

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41 minutes ago, mimbecky said:

I heard this when I woke up.  Funny I was going to specifically ask YOU why this could be so.  It seems counter intuitive that a first 1/2 dose would be more effective than 2 full doses. Do you know when that human adenovector data is due?  Or Johnson and Johnson (isn't that a human adenovirus?) data?

Fascinating stuff - 

Yes the J&J/Janssen vaccine uses non-replicating human adenovector technology.  They are actually enrolling two large phase 3 trials (called Ensemble I and Ensemble II).   The first is a single injection. The second is two injections one month apart.  The Russian Sputnik vaccine and the Chinese (CanSino) COVID vaccines also use human adenovectors.  A bit different forms.  Yes fascinating indeed!  The J&J technology is currently being used in an approved Ebola vaccine so there is already human experience with it.

Edited by TeeRick
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1 hour ago, mimbecky said:

I heard this when I woke up.  Funny I was going to specifically ask YOU why this could be so.  It seems counter intuitive that a first 1/2 dose would be more effective than 2 full doses. Do you know when that human adenovector data is due?  Or Johnson and Johnson (isn't that a human adenovirus?) data?

Fascinating stuff - 


I’d like some data on this, but it’s possible they’re getting an anti-vector response at the higher dose and that’s curtailing their immune response on the second dose. That would make some sense, but it could be something completely different. 
 

The reviewers may want to look at that phenomenon, so hopefully AZ and Oxford are trying to understand it. It could impact booster schedules, for instance. 
 

But generally good news, I think. 

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15 hours ago, LuAnn said:

Perhaps I missed this along the way of reading posts but do you all think that the Covid immunization will be required to sail with Celebrity and/or any cruise lines? 

I can see this being a requirement to get on any cruise ship along with rapid testing before boarding for 2021 and 2022. Additionally I can see,  once a vaccine is available most International airlines and destinations may have the same requirements.

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11 minutes ago, markeb said:


I’d like some data on this, but it’s possible they’re getting an anti-vector response at the higher dose and that’s curtailing their immune response on the second dose. That would make some sense, but it could be something completely different. 
 

The reviewers may want to look at that phenomenon, so hopefully AZ and Oxford are trying to understand it. It could impact booster schedules, for instance. 
 

But generally good news, I think. 

Yes definitely boosting schedules.  My own research experience with vectored approaches (pox vectors mostly) is that this is a known risk.  That is why the preclinical prime-boost protocols developed have generally been vector-prime followed by subunit-boost.  This might be needed in people too.  But way more clinical trials to sort it all out.

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28 minutes ago, mimbecky said:

English please.

Layman's terms?

😂

 

I'll try...

 

Once upon a time, most vaccines used either a killed whole pathogen (virus or bacteria), or a live but modified whole pathogen that no longer caused disease. Those worked well for a lot of pathogens, but they tended to cause more significant reactions (especially for killed pathogens) or posed at least a theoretical risk of returning to virulence (able to cause disease).

 

Most work over the last few decades has revolved around subunit vaccines. Those produce one or more specific proteins, or more typically parts of a protein, by fermentation in another organism (yeast, E. coli, etc.) by implanting the DNA to code for the protein by recombinant methods. That's worked very well for a lot of pathogens.

 

There has been a lot of research, mostly pre-clinical, on using either a virus (the vector mentioned above) or DNA coding for a protein (a lot of the work revolved around implanting the DNA on very tiny gold beads and using an electrostatic device to get them into the living layers of the skin). Those technologies were very successful in studies at stimulating an immune response, but it wasn't always very robust, and it didn't always last very long. A number of those studies found that if you used either DNA alone or a virus vector to introduce DNA or potentially RNA to code for a protein that could produce protection, and then followed it up with a subunit (the actual recombinant protein), you could get both a good initial immune response, often for pathogens where that immune response was difficult to produce, and a robust and lasting immune response.

 

Prime-boost strategies (the terminology usually applied to those techniques) have largely been a pre-clinical/lab thing. From a regulatory standpoint, they're two different products with their own safety profiles, that then have to be used together to achieve immunity. And most of the work has been done on "hard pathogens" and frequently orphan pathogens (Ebola, Marburg, Lassa, etc.) with little or no market to support the work.

 

What Rick and I were discussing is the risk of using a viral vector that can produce its own immune response, which could hinder the response to a second dose, or to an actual booster down the road, whether that's annual, every five years, or longer. The theory would be to take advantage of the vector based vaccines ability to stimulate a good initial immune response, including T-cells that would be vital to a secondary response, to prime the immune system (like priming a pump) and add the potential of a subunit vaccine to boost the response as a second (or third if needed) dose.

 

The mRNA vaccines are kind of unique in this discussion as they seem to behave like a subunit vaccine, and you wouldn't expect an immune response to the RNA. Novovax (at least, maybe others) is working on a traditional subunit vaccine.

 

Hope that makes sense, and helps!

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mimbecky so sorry as I was responding to markeb's comment and forgot where I was!  Yes plain and hopefully simple.  So here goes.  Or anybody feel free to just scroll on by!

 

The most common prime - boost is your typical two shot protein subunit vaccine like Shingrix or Hepatitis B vaccine.  The first shot "primes" the immune system and the second shot results in the "boost" (amplification) of the response and greatly aids in the the longevity and memory of the response.  COVID vaccines being developed by Novavax and by GSK use this approach with purified SPIKE protein. 

 

So what about COVID adenovector vaccines?  Adenovirus is one of our common cold viruses.

The AZ/Oxford vaccine expresses a COVID protein (SPIKE) in a monkey adenovirus vector.   It might possibly be recognized as "foreign" to our immune systems and we mount an attack against the vector itself or something that it produces in addition to SPIKE - probably in the first dose or priming dose.  So the second boost dose is possibly less effective.  It is possible to get around this response against the vector by using human adenovirus vectors (Ad5 and Ad26) instead of monkey.  As they have survived in humans they are adapted.  So J&J (Ad26) and others use this approach. 

 

This is unlike the mRNA vaccines (Pfizer, Moderna) which are actually simpler and just express SPIKE only - no vector, no other components. So the Boost (second) dose is very effective.

 

In a variation of the protocol, the two doses can be a bit different in their prime-boost components.  This can be a prime with one human adenovector (say Ad5) and boost with a different human adenovector (Ad26).  Both express the SPIKE protein but they are slightly different adenoviruses. So our immune response against the vector is lessened but we still make strong responses against the COVID protein.  The Russian Sputnik vaccine uses this approach for example (Ad5 and Ad26).

 

Finally the technologies themselves can be mixed in the protocol.  The Prime dose (adenovector) might be followed by the purified protein subunit Boost.  This helps get around the initial response against the vector alone.  This has not been tried in people (yet).

 

 

Edited by TeeRick
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5 minutes ago, markeb said:

 

I'll try...

 

Once upon a time, most vaccines used either a killed whole pathogen (virus or bacteria), or a live but modified whole pathogen that no longer caused disease. Those worked well for a lot of pathogens, but they tended to cause more significant reactions (especially for killed pathogens) or posed at least a theoretical risk of returning to virulence (able to cause disease).

 

Most work over the last few decades has revolved around subunit vaccines. Those produce one or more specific proteins, or more typically parts of a protein, by fermentation in another organism (yeast, E. coli, etc.) by implanting the DNA to code for the protein by recombinant methods. That's worked very well for a lot of pathogens.

 

There has been a lot of research, mostly pre-clinical, on using either a virus (the vector mentioned above) or DNA coding for a protein (a lot of the work revolved around implanting the DNA on very tiny gold beads and using an electrostatic device to get them into the living layers of the skin). Those technologies were very successful in studies at stimulating an immune response, but it wasn't always very robust, and it didn't always last very long. A number of those studies found that if you used either DNA alone or a virus vector to introduce DNA or potentially RNA to code for a protein that could produce protection, and then followed it up with a subunit (the actual recombinant protein), you could get both a good initial immune response, often for pathogens where that immune response was difficult to produce, and a robust and lasting immune response.

 

Prime-boost strategies (the terminology usually applied to those techniques) have largely been a pre-clinical/lab thing. From a regulatory standpoint, they're two different products with their own safety profiles, that then have to be used together to achieve immunity. And most of the work has been done on "hard pathogens" and frequently orphan pathogens (Ebola, Marburg, Lassa, etc.) with little or no market to support the work.

 

What Rick and I were discussing is the risk of using a viral vector that can produce its own immune response, which could hinder the response to a second dose, or to an actual booster down the road, whether that's annual, every five years, or longer. The theory would be to take advantage of the vector based vaccines ability to stimulate a good initial immune response, including T-cells that would be vital to a secondary response, to prime the immune system (like priming a pump) and add the potential of a subunit vaccine to boost the response as a second (or third if needed) dose.

 

The mRNA vaccines are kind of unique in this discussion as they seem to behave like a subunit vaccine, and you wouldn't expect an immune response to the RNA. Novovax (at least, maybe others) is working on a traditional subunit vaccine.

 

Hope that makes sense, and helps!

Thanks Mark- I took a different approach but I think we both answered the question and ended up at the same place.  

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2 minutes ago, TeeRick said:

Thanks Mark- I took a different approach but I think we both answered the question and ended up at the same place.  

 

Typing at the same time...

 

Yeah. Same destination, different routes!

 

😀

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Although the data has not been released or published, some interesting tidbits about the AZ/Oxford vaccine results announced recently.

- very inexpensive to manufacture and distribute, making it a good candidate for a "worldwide" vaccine and AZ has vowed to not take a profit from it during the pandemic period.

- ultralow freezer temperatures not necessary, stable in refrigerator.

- there is a statement about the results showing reduction in infections and in asymptomatic people - after using a nasal swab approach every few days.  Very good if that holds up.  

- 90% efficacy can be achieved by just adjusting the first dose to 1/2 the amount.  This actually stretches out the quantity of the vaccine available to the public if you do the simple math.

 

https://www.bbc.com/news/health-55040635

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Thank you all you science guys for keeping this thread going, keeping it up to date, and explaining so, so much.

 

For those of us who are not scientifically inclined, and sometimes struggle with the info, I found this explanation of the various vaccines helpful.

 

https://www.cbc.ca/news/health/covid-vaccines-canada-profiles-1.5708240

 

Note: this is a Canadian article and is talking about the vaccines that Canada has reserved and the dose reservation mentioned is for Canada not UK,  USA, EU, etc.

 

Again, thanks for the thread,

Cheers, h 🥂.

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Yes thanks for further explanation although I had to read both several times and will probably read them again tomorrow.  I think you are saying that our bodies might be mounting an attack on the vector which then could cause interference in allowing the important part of the vaccine to do its work.  By only giving a half dose at first, the second dose may be less hindered in doing its job. 

I might be way off but that is what I gleaned. Otherwise, I give up on understanding and will just be glad there are scientists who know what it is going on.

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15 hours ago, TeeRick said:

Oxford/AZ vaccine efficacy results just released.  This is the monkey adenovector vaccine.  One dosing protocol resulted in 90% efficacy.  That as a 1/2 dose followed by a full dose at 30 days.

 

Of interest- two full doses a month apart gave only 62% efficacy.  So what leads to these differences?  And why different from the two mRNA vaccines?  Lot's of possibilities starting with immune moderating effects of the adenovector itself.  There are human adenovector versions of this vaccine in phase 3 so we shall see soon if this was a species-related result (monkey vs human).  That has happened before with the vaccines for rotavirus.   We shall see.  It is nice that their are multiple approaches.  

 

https://www.cnbc.com/2020/11/23/oxford-astrazeneca-covid-vaccine-is-70percent-effective-trial-shows-.html

Brings whole new meaning to the dose response curve

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13 hours ago, markeb said:


I’d like some data on this, but it’s possible they’re getting an anti-vector response at the higher dose and that’s curtailing their immune response on the second dose. That would make some sense, but it could be something completely different. 
 

The reviewers may want to look at that phenomenon, so hopefully AZ and Oxford are trying to understand it. It could impact booster schedules, for instance. 
 

But generally good news, I think. 

That could raise some interesting questions about follow on booster shots with the AZ vaccine.

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18 hours ago, terrydtx said:

I can see this being a requirement to get on any cruise ship along with rapid testing before boarding for 2021 and 2022. Additionally I can see,  once a vaccine is available most International airlines and destinations may have the same requirements.

Agreed, and Quantas already announced that they will require the vaccine in the future.https://www.bbc.com/news/amp/world-australia-55048438

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7 hours ago, mimbecky said:

Yes thanks for further explanation although I had to read both several times and will probably read them again tomorrow.  I think you are saying that our bodies might be mounting an attack on the vector which then could cause interference in allowing the important part of the vaccine to do its work.  By only giving a half dose at first, the second dose may be less hindered in doing its job. 

I might be way off but that is what I gleaned. Otherwise, I give up on understanding and will just be glad there are scientists who know what it is going on.


Why couldn’t I have written that?

 

That’s a perfect summary. 

Edited by markeb
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Moderna Chief Medical Officer warns public should not "over-interpret" the vaccine trial results to assume life could go back to normal after adults are vaccinated. "They do not show that they prevent you from potentially carrying this virus transiently and infecting others. I think it's important that we don't change behavior solely on the basis of vaccination."  Which means keep social distancing and wearing masks and hand hygiene.
 
While he believes based on the science that it's likely that vaccine does prevent transmission, there's still no solid proof of that.
 
Hopefully there will be proof by the time cruising eventually starts up next year.
Edited by twins_to_alaska
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1 hour ago, twins_to_alaska said:
Moderna Chief Medical Officer warns public should not "over-interpret" the vaccine trial results to assume life could go back to normal after adults are vaccinated. "They do not show that they prevent you from potentially carrying this virus transiently and infecting others. I think it's important that we don't change behavior solely on the basis of vaccination."  Which means keep social distancing and wearing masks and hand hygiene.
 
While he believes based on the science that it's likely that vaccine does prevent transmission, there's still no solid proof of that.
 
Hopefully there will be proof by the time cruising eventually starts up next year.

Yes we have had quite a lot of discussion on this thread and elsewhere on this very topic.

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Thank you so much for all your amazing knowledge and willingness to share it. You are all doing a great public service.

 

Scary thing is I am sitting right now in Ottawa Canada. The first story last evening was the vaccine and it was presented as the solution and that everything will be solved. 

 

I recently shared earlier on this thread a National Post article that emphasized that this may well not be the case. Now the evening more clear clarification from Moderna (thanks for sharing).

 

But.....this caution is obviously not being disseminated to the public, at least not here and elsewhere.

I am quite concerned the public is not being suitably informed.

 

 

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5 minutes ago, ABoatNerd said:

Thank you so much for all your amazing knowledge and willingness to share it. You are all doing a great public service.

 

Scary thing is I am sitting right now in Ottawa Canada. The first story last evening was the vaccine and it was presented as the solution and that everything will be solved. 

 

I recently shared earlier on this thread a National Post article that emphasized that this may well not be the case. Now the evening more clear clarification from Moderna (thanks for sharing).

 

But.....this caution is obviously not being disseminated to the public, at least not here and elsewhere.

I am quite concerned the public is not being suitably informed.

 

 

I have stated here and elsewhere that the messaging and education to the public is critical to COVID vaccine success.  So I totally agree with you.  I am pretty convinced that those in charge of this in various countries will do so.  But they really need to wait for an approved vaccine before they can communicate about it.  In the US anyway the EUA for the Pfizer vaccine could come after the Dec 10th meeting.  But it would be premature to communicate anything before then.

 

Also the communications can only state what the vaccines actually did in the clinical trials (efficacy and safety).  And expected side effects.  I do not think that they will focus on preventing transmission - but more in preventing disease and severity.  Only the AZ/Oxford vaccine in a limited way attempted to measure virus in nasal swabs at some frequency in their trial.  They have made positive statements about this but no data yet.  In my somewhat educated opinion (or speculation), if the adenovector vaccines are found to also prevent transmission, then the mRNA vaccines will do so as well given the consistencies of the immune responses between them.

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Not taking anything away from the progress made by Pfyzer and Moderna, but hearing about AstraZeneca's progress yesterday was definitely very uplifting, especially from a global perspective. One big reason was this:

 

What’s more, the AstraZeneca/Oxford vaccine cuts transmission of the virus by reducing the number of asymptomatic infections, the vaccine developers reported.That’s critical because we know that a lot of transmission of SARS-CoV-2 is from asymptomatic people,” said Gandhi during a Nov. 23 news briefing of the Infectious Diseases Society of America. It’s unclear whether the vaccines from Pfizer or Moderna reduce transmission.

 

Another reason was this: 

 

 

AstraZeneca’s vaccine may be easier to distribute than those from Pfizer and its German collaborator BioNTech and from Moderna because the vaccine doesn’t need to be frozen as the other two do (SN: 11/16/20; SN: 11/18/20; SN: 11/20/20). It can be stored at temperatures found in regular refrigerators, unlike the special freezers needed for the Pfizer vaccine.

AstraZeneca says it has the capacity to produce 3 billion doses of its vaccine in 2021.

 

But, it's all good

 

https://www.sciencenews.org/article/coronavirus-covid-19-oxford-astrazeneca-vaccine-effective

 

 

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22 hours ago, terrydtx said:

I can see this being a requirement to get on any cruise ship along with rapid testing before boarding for 2021 and 2022. Additionally I can see,  once a vaccine is available most International airlines and destinations may have the same requirements.

 

I have absolutely NO problem with that.  IMO, that's the only way to get us cruising again.  

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9 hours ago, nocl said:

That could raise some interesting questions about follow on booster shots with the AZ vaccine.

 Yes, seems we would eventually run out of "safe" but "unrecognized" adenoviruses to carry in the spike. ??

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