Are vaccines the light at the end of the tunnel?

[ipeeinthepool]

All great news.  Ill be first in line.

[Ken the cruiser]

7 minutes ago, Arizona Wildcat said:

The issues with a vaccine are vaccines for viruses are usually are 60% of less effective along with the older the person the smaller the number of antibodies they produce.

 

Both my DW and I are in our late 60s and in the last 3 years, besides the annual flu shots to include one the other day, we have received shots for Hep A, Japanese Encephalitis, Pneumonia, Tetnus, Typhoid, Shingles and the MMR.

 

So, here's my question. Are our older immune systems more receptive because of this to trigger new antibodies and t-cells to fight off a targeted virus or are we simply doomed to have weaker immune systems the older we get regardless of what we do?

[markeb]

41 minutes ago, Ken the cruiser said:

So, here's my question. Are our older immune systems more receptive because of this to trigger new antibodies and t-cells to fight off a targeted virus or are we simply doomed to have weaker immune systems the older we get regardless of what we do?

 

Hard to say. Certainly, on the average, the older we get, we either get a weaker immune response, or an inappropriate immune response. But that's on average, and there's a distribution around the mean, so some people's immune systems are going to be on the right hand side of curve and overlap with the left hand side of a younger immune system. We only understand the subtleties of aging so much...

 

Same thing most likely on the first part of your question. The more times mammalian cells divide, the more mistakes occur, and the more problems natural process have in correcting the mistakes. So maybe that's less ability to respond, or maybe it's an error in the response such as you see in autoimmune disorders, or hematologic cancers. Or, maybe you as an individual deviate from the mean and respond just fine. Biology is fun...

[Ken the cruiser]

2 minutes ago, markeb said:

 

Hard to say. Certainly, on the average, the older we get, we either get a weaker immune response, or an inappropriate immune response. But that's on average, and there's a distribution around the mean, so some people's immune systems are going to be on the right hand side of curve and overlap with the left hand side of a younger immune system. We only understand the subtleties of aging so much...

 

Same thing most likely on the first part of your question. The more times mammalian cells divide, the more mistakes occur, and the more problems natural process have in correcting the mistakes. So maybe that's less ability to respond, or maybe it's an error in the response such as you see in autoimmune disorders, or hematologic cancers. Or, maybe you as an individual deviate from the mean and respond just fine. Biology is fun...

Well, there you go then. I guess we'll just continue to watch our weight, practise good personal hygiene, eat healthy, keep a positive attitude and hope for the best! 😁😁

[markeb]

6 minutes ago, Ken the cruiser said:

Well, there you go then. I guess we'll just continue to watch our weight, practise good personal hygiene, eat healthy, keep a positive attitude and hope for the best! 😁😁

 

It won't hurt. It may help. And I think most people believe that better overall health is more likely to make you better able to respond to infectious disease.

 

There are those folks who live to 104 or even longer...

 

And then there are giant sea turtles!

Edited September 6, 2020 by markeb

[markeb]

1 hour ago, Arizona Wildcat said:

There are numerous facilities FDA approved that can produce millions of does every month.  Availability in the US and Canada will not be an issue - no idea about elsewhere - as plenty contracted and US has small population and Canada smaller.

The issues with a vaccine are vaccines for viruses are usually are 60% of less effective along with the older the person the smaller the number of antibodies they produce.

 

 

It's really not as simple as total doses. It's going to be paired doses (same vaccine for the same person). And there's a very real possibility that different vaccines will have different efficacies in different people. We just don't know.

 

If you have 50M doses of vaccine A, 50M of vaccine B, and 50M of vaccine C, and each require a two-dose series, you can vaccinate at most 75M people, and at least initially, someone who receives a first dose of vaccine A will need their second dose to also be vaccine A, not B or C; there won't be data on mixing and matching.

 

And efficacy is TBD, and whether antibody response is actually the governing factor is also TBD. It's just what people understand.

[TeeRick]

10 hours ago, Arizona Wildcat said:

There are numerous facilities FDA approved that can produce millions of does every month.  Availability in the US and Canada will not be an issue - no idea about elsewhere - as plenty contracted and US has small population and Canada smaller.

The issues with a vaccine are vaccines for viruses are usually are 60% of less effective along with the older the person the smaller the number of antibodies they produce.

 

Just not true as a general statement.  Vaccines against many viruses are highly effective.  Maybe not influenza vaccine which might be 60% some years.

[Arizona Wildcat]

4 hours ago, TeeRick said:

Just not true as a general statement.  Vaccines against many viruses are highly effective.  Maybe not influenza vaccine which might be 60% some years.

Rick - my statement does have a typo.  Sorry.  Should have said or instead of "of".  There are viruses that are almost 100% controlled such as smallpox.  rDNA viruses like flu easily mutate and for whatever reason - I am not a doctor - the multiple strains are not all in the vaccine.   Viruses are not all like flu.

[Arizona Wildcat]

13 hours ago, markeb said:

 

It's really not as simple as total doses. It's going to be paired doses (same vaccine for the same person). And there's a very real possibility that different vaccines will have different efficacies in different people. We just don't know.

 

If you have 50M doses of vaccine A, 50M of vaccine B, and 50M of vaccine C, and each require a two-dose series, you can vaccinate at most 75M people, and at least initially, someone who receives a first dose of vaccine A will need their second dose to also be vaccine A, not B or C; there won't be data on mixing and matching.

 

And efficacy is TBD, and whether antibody response is actually the governing factor is also TBD. It's just what people understand.

Agree.  You are assuming it will be a 2 dose series.  At this point we do not know.  I agree that every person will produce a different antibody count and if the CDC is correct the number of antibodies produced usually decreases as we get older.

I have no idea when a vaccine will become available, how effective it will be for various ahe groups or how long to generate antibodies.  I do know that the drug companies are working together and that a billion doses could be available 90 days after approval.

I speculate that people not wanting to be first or not wanting vaccination at all will be the issue.  Hope there are few to no side effects from COVID vaccine.  The new shingles vaccine put me down on my back for 2 days.  The one for yellow fever was far worse.

[markeb]

20 minutes ago, Arizona Wildcat said:

Agree.  You are assuming it will be a 2 dose series.  At this point we do not know.  I agree that every person will produce a different antibody count and if the CDC is correct the number of antibodies produced usually decreases as we get older.

 

It's been a couple of weeks since I looked, but all of the vaccines in US trials if memory serves were looking at two doses, either 0-14 or 0-30 (days). I think AZ may have had an arm looking at only one dose, but they have something like 30 (exaggeration) arms in their clinical trial!

 

Yellow fever vaccine was always notorious. It was in the battery of required vaccines in the Army in the '80s...

[Arizona Wildcat]

35 minutes ago, markeb said:

 

It's been a couple of weeks since I looked, but all of the vaccines in US trials if memory serves were looking at two doses, either 0-14 or 0-30 (days). I think AZ may have had an arm looking at only one dose, but they have something like 30 (exaggeration) arms in their clinical trial!

 

Yellow fever vaccine was always notorious. It was in the battery of required vaccines in the Army in the '80s...

I think the attached link from CBC might be interesting as to why Canada unlikely to open up any time soon.  It is sort of the same problem the US is experiencing in SD and surrounding states that previously had VERY low COVID counts.

https://www.cbc.ca/news/health/covid19-immunity-canada-1.5704172

My info is mostly of the Moderna vaccine that has some thousands of volunteers locally in a phase 3 trail.  If the info on CNBC morning show yesterday is correct and one or more vaccines receive emergency approval approx November 1st numbers of 1 billion doses available in 2020 and 8 billion next year were stated.  Those numbers might be high but, for example, there is a small private lab capable of producing a million doses a week using only one shift.  Once approved pharma will gear up quickly with the billions of government money that have been "thrown" their way from many countries.

[Fouremco]

There's a lot of interesting information, some of it historical in nature, in this article. While it deals with setting Canadian priorities for Covid-19 vaccinations, the subject matter is actually quite a bit broader and well worth a read by anyone:

 

https://www.huffingtonpost.ca/entry/covid-19-vaccine-campaign-canada_ca_5f524fe7c5b62b3add3f9974??ncid=newsltcahpmgnews

[BP99]

3 hours ago, Arizona Wildcat said:

Rick - my statement does have a typo.  Sorry.  Should have said or instead of "of".  There are viruses that are almost 100% controlled such as smallpox.  rDNA viruses like flu easily mutate and for whatever reason - I am not a doctor - the multiple strains are not all in the vaccine.   Viruses are not all like flu.

Huh? I am not a virologist but for some friendly clarification:

Flu viruses (Influenza) are RNA viruses. I'm not sure what you mean by a rDNA

virus?? rDNA usually means "recombinant DNA".

The flu virus uses an enzyme (RNA dependant RNA polymerase) to replicate

that does not have proofreading and thus makes errors and causes mutations.

Flu viruses have a segmented genome and can swap genes with other flu

viruses.

[OceanCruise]

On 9/2/2020 at 2:54 PM, markeb said:

 

 

 

So yes, I've read more articles than you can imagine on this. They're almost all from way back in the spring, and they've all had some design flaws.

 

 

If you are only looking at studies from the spring you are very misinformed on the issue. Clearly you haven't read the dozens of further studies that have come out over the summer regarding Covid therapeutics which are all are linked at: c19study.com and include a number of meta-analyses and some randomized controlled-trials. Are you aware that 2 of the major, early negative highly reported studies in the Lancet and NEJM were later retracted? What alternative treatment are you proposing as a pre-hospital intervention other than waiting for a vaccine that may or may not work and may or not be found to be safe as time goes by?  I would personally choose a medication that has been used safely for 60 years (and is sold over the counter in various countries), has shown promising results in many research studies, and for which many doctors actually treating patients (not beaurocrats) say is effective for early-stage treatment. 

[markeb]

1 minute ago, OceanCruise said:

Are you aware that 2 of the major, early negative highly reported studies in the Lancet and NEJM were later retracted?

 

Yes. I've already said that. Those were the studies that appeared to show cardiotoxicity. The dataset could not be verified, and the studies were withdrawn. The original results were more than a little surprising, and I'm much less surprised they couldn't be verified.

 

I'm not a physician. Pre-hospital intervention has not even been shown to be necessary. Ideally, you'd intervene with something with more antiviral activity than HCQ or doxy or azithromycin, but by the time you actually have a diagnosis, given the asymptomatic period, it's unclear how effective any antiviral would be; once you damage enough cells, it's about the inflammatory response.

 

The first 2-3 links on your web page went to 404 file not found when you tried to go to the primary source. One study is a very good safety study on HCQ in RA and I believe SLE. Not surprising results. No, it's shown mixed results at best that have been interpreted by those with an agenda as extremely promising. I actually tried to follow the studies out of curiosity and gave up when the references went nowhere, the, doi numbers went nowhere, and in at least one case, even the primary author went nowhere.

 

Case series with no control group are interesting at best. If they show promise, they tend to trigger actual controlled studies. The NIH multi-center study was randomized and placebo controlled. It found no benefit in hospitalized patients. That was in June. There are currently 250 clinical trials listed globally using HCQ. Many are actually placebo controlled. A few are looking at HCQ versus one or more broad-spectrum antivirals. Only a small handful have completed, and without looking at all 250 (probably less than 25 completed), I may have found one that has gone to publication, but its results are still under review.. A number have been suspended, terminated, or withdrawn for various reasons, including a drop of cases in the study area. Many of those studies with some actual scientific rigor are looking at the pre-hospital setting, but most of them won't finish for months, and won't go to publication for some time after that. 

[mayleeman]

General question on Phase 3 trials: Let's say they have a trial with 30,000 volunteers. Half get vax, half placebo.

 

From what I understand, the vaccines may have varying levels of antibody response in different people, and that seems like it could vary due to the virus load in any exposure experienced.  It seems mask-wearing by surrounding people could be a major variable in viral load. I don't think they will purposely expose anyone.

 

Maybe this is a naive question or based on a misunderstanding of how success is measured, but how do they control for viral load in measuring success?

[markeb]

1 hour ago, mayleeman said:

General question on Phase 3 trials: Let's say they have a trial with 30,000 volunteers. Half get vax, half placebo.

 

From what I understand, the vaccines may have varying levels of antibody response in different people, and that seems like it could vary due to the virus load in any exposure experienced.  It seems mask-wearing by surrounding people could be a major variable in viral load. I don't think they will purposely expose anyone.

 

Maybe this is a naive question or based on a misunderstanding of how success is measured, but how do they control for viral load in measuring success?

 

You ask people to not alter their routine, although some will. Fortunately, you don't know if you got the vaccine or the placebo, so the exposure probability (and viral load from exposure) should be roughly the same between the vaccinated group and the control group. The size of the trial is to give you statistical power to see a difference.

 

Not easy, but it's how these things are normally done. Depending on the trial, there are multiple endpoints which make subtle differences potentially even more subtle. I'd have to look again; I assume most of the trials are checking titres at some point after the initial vaccine or initial series. But other endpoints are going to be whether or not there's actual disease, whether or not you recover the virus on nasal swab, hospitalization comparison between the groups, and I guess somewhat obviously, mortality.

[npcl]

2 hours ago, mayleeman said:

General question on Phase 3 trials: Let's say they have a trial with 30,000 volunteers. Half get vax, half placebo.

 

From what I understand, the vaccines may have varying levels of antibody response in different people, and that seems like it could vary due to the virus load in any exposure experienced.  It seems mask-wearing by surrounding people could be a major variable in viral load. I don't think they will purposely expose anyone.

 

Maybe this is a naive question or based on a misunderstanding of how success is measured, but how do they control for viral load in measuring success?

In my experience the participants in the trial are instructed in best practices for avoiding the illness.  All participants receive the same instructions.  They are also informed that they may or may not have gotten the vaccine.

 

In a trial for something like this there is no way to control individual behaviors, nor do you even try.  It really comes down to statistical analysis with a large enough sample size to determine that the difference is do to the drug being tested and not individual behaviors or individual differences.

 

After the trial reaches an end point the data will be anaylzed in a number of different ways looking at different locations, age groups, gender, race, etc. to see if there were differences in a number of sub groups. 

 

Just as an example you might see a more of a difference in an area where mask use was mandated than one where it was not.  If you did then you would start looking for reasons why such a difference might occur.  If it was important enough you might even design a follow on trial to test specifically for some item or another.

[mayleeman]

4 hours ago, npcl said:

large enough sample size to determine that the difference is do to the drug

 

The need for a large sample, plus ensuring it covers the demographic variables you mentioned, seems to me to be a huge obstacle to fast-tracking.

Edited September 8, 2020 by mayleeman

[npcl]

5 minutes ago, mayleeman said:

 

The need for a large sample, plus ensuring it covers the demographic variables you mentioned, seems to me to be a huge obstacle to fast-tracking.

Actually for a trial of this type the larger the enrollment the faster you can get enough data for a successful analysis.     The demographic analysis (while you do try and get a wide coverage in the trial) is more a post trial analysis to see if there are differences in either effectiveness or safety in various groups that might impact the label of the product.

[TeeRick]

10 hours ago, mayleeman said:

 

The need for a large sample, plus ensuring it covers the demographic variables you mentioned, seems to me to be a huge obstacle to fast-tracking.

I have been involved with vaccine trials with tens of thousands of healthy volunteers.  And for pediatric vaccines even higher numbers.  In general these have taken several years to complete and analyze.  But a COVID vaccine trial looking at immune responses and hopefully correlated to protection from virus will be straight forward and the time frame will be reasonable.  There are lots of healthy volunteers, elderly, risk groups etc that really want to participate.  At least in the lead phase 3 trials that have started.  And the virus is still everywhere.  So that makes conditions for these trials very doable.

[TeeRick]

21 hours ago, OceanCruise said:

If you are only looking at studies from the spring you are very misinformed on the issue. Clearly you haven't read the dozens of further studies that have come out over the summer regarding Covid therapeutics which are all are linked at: c19study.com and include a number of meta-analyses and some randomized controlled-trials. Are you aware that 2 of the major, early negative highly reported studies in the Lancet and NEJM were later retracted? What alternative treatment are you proposing as a pre-hospital intervention other than waiting for a vaccine that may or may not work and may or not be found to be safe as time goes by?  I would personally choose a medication that has been used safely for 60 years (and is sold over the counter in various countries), has shown promising results in many research studies, and for which many doctors actually treating patients (not beaurocrats) say is effective for early-stage treatment. 

OceanCruise,

This has been a highly informative vaccine thread on a cruise board and it is a topic highly relevant to the restart of cruising and the future of cruising.  While I hope that effective COVID-19 therapeutics will be developed, and there are many such drugs in development, that is not the topic here.  If you have an opinion one way or another on hydroxychloroquine as many people do, please realize that it is not our topic here.  Plenty of other places to discuss this.  Thank you and be well.

[Arizona Wildcat]

Interesting article in USA Today.  They stated that COVID vaccine will be distributed through McKesson in the US.  They certainly have a wide distribution network.

They explained the packaging for the various vaccines, shelf life one shipped and after vials are at a site to be administered.  There was a large variation from a shelf life of a couple days to a week or possibly more.

More interesting to myself was that some vaccines - think J&J - could be stored at temperatures workable for local pharmacies; while others required very low temps and to be frozen using dry ice for most retail outlets.

For vaccines requiring super cold wouldn't that be difficult in rural areas?

Locally, our county health stated they would partner with both hospitals and pharmacies to have innoculation clinics.

No discussion about a time line.

 

[Arizona Wildcat]

3 hours ago, TeeRick said:

I have been involved with vaccine trials with tens of thousands of healthy volunteers.  And for pediatric vaccines even higher numbers.  In general these have taken several years to complete and analyze.  But a COVID vaccine trial looking at immune responses and hopefully correlated to protection from virus will be straight forward and the time frame will be reasonable.  There are lots of healthy volunteers, elderly, risk groups etc that really want to participate.  At least in the lead phase 3 trials that have started.  And the virus is still everywhere.  So that makes conditions for these trials very doable.

Agree.  Found this in the New York Times.  Gives a picture outside North America and mentions a time frame.

Japan approved a plan to spend more than $6 billion from its emergency budget reserves on coronavirus vaccines. The chief cabinet secretary, Yoshihide Suga, told reporters that AstraZeneca had agreed to supply 120 million doses starting early next year, and that Pfizer would supply 120 million doses by the end of June. Mr. Suga said the government was also negotiating with Moderna for more than 40 million additional doses

[npcl]

2 hours ago, Arizona Wildcat said:

Interesting article in USA Today.  They stated that COVID vaccine will be distributed through McKesson in the US.  They certainly have a wide distribution network.

They explained the packaging for the various vaccines, shelf life one shipped and after vials are at a site to be administered.  There was a large variation from a shelf life of a couple days to a week or possibly more.

More interesting to myself was that some vaccines - think J&J - could be stored at temperatures workable for local pharmacies; while others required very low temps and to be frozen using dry ice for most retail outlets.

For vaccines requiring super cold wouldn't that be difficult in rural areas?

Locally, our county health stated they would partner with both hospitals and pharmacies to have innoculation clinics.

No discussion about a time line.

 

There are three large scale distributors of pharmaceutical products in the US, Mckesson, Cardinal Health and AmerisourceBergen.  I would expect all three to be involved if the distribution goes through normal commercial channels. Between the 3 over 100 distribution centers in the US.

Edited September 8, 2020 by npcl