Are vaccines the light at the end of the tunnel?

[phoenix_dream]

45 minutes ago, markeb said:

 

Sadly, I think you're probably right.

 

And I think you vaccinate the institutionalized population as soon as possible to stop transmission in that population, and to reduce the risk they infect staff, who infect their grandparents, etc. And you take that population rapidly out of the susceptible population.

 

I'm doubtful there will be data on under 5 at licensure, but maybe? So that may be a theoretical point for a few months. But that's going to be a heck of a conversation with a pediatrician if there is no data. I think you vaccinate them regardless of immune status, if the data supports 'regardless of immune status' at entry into kindergarten, once the data supports the age group.

 

But I'm a public health guy these days, not in human patient care...

Regarding risk to the staff at the jails, I certainly think the staff should be vaccinated early on.  Their job is rough enough to begin with!  And I am not a prison expert (thankfully!) but it would seem to me that if they vaccinate the staff, and then find a way to quarantine new prisoners for 14 days or whatever the current contagion time is estimated, they could delay vaccinating everyone.  Won't happen, but it could.

[phoenix_dream]

8 hours ago, TeeRick said:

I think that prioritizing by severity of crime will be a constitutional issue and not likely.  Even those on death row.  Very interesting legal and human rights battles ahead I think.  However if prisoners are simply treated like the general US population, then they can be prioritized based on age and health just like the rest of us.  Prisoners over 65+ for example.

I agree with what you are saying.  It still seems sad to me that there will be those who fight for prisoners who have created heinous crimes, rather than fighting to save the lives of healthy seniors.   I doubt they will prioritize them (prisoners) like the rest of us - too much paperwork and bureaucracy - not the government's finest skills for sure.  And based on the proposal we were discussing, there is no priority for people over 65 that I can see, at least the healthy ones.  I don't think they are considering age an underlying condition, or they wouldn't be specifically mentioning seniors in nursing homes, etc.  All they would need to say is people 65+.  I know it is too early to know what will finally happen, but going by the specific wording as a healthy 69 year old I would be at the end of the pack.  Time will tell.

[markeb]

10 minutes ago, phoenix_dream said:

Regarding risk to the staff at the jails, I certainly think the staff should be vaccinated early on.  Their job is rough enough to begin with!  And I am not a prison expert (thankfully!) but it would seem to me that if they vaccinate the staff, and then find a way to quarantine new prisoners for 14 days or whatever the current contagion time is estimated, they could delay vaccinating everyone.  Won't happen, but it could.

 

It's almost impossible to say anything here and stay out of politics, but I'm going to try to stay with on a public health track...

 

There are roughly 2.3M incarcerated persons in the US. Somewhere around 550,000 of those are in pre-trial confinement and under the US and state constitutions are presumed innocent. That population is almost impossible to actually characterize for a number of reasons. Presumably a majority in that population have never been convicted of anything (some almost certainly have). They're in local jails for the most part, which are by design somewhat rotating doors (DUI comes in for 1-3 nights and leaves, etc. Pre-trial confinement stays.). So the DUI comes in with COVID19, passes it to the pre-trial confinement case, who finally makes bail, has charges dropped, someone realizes they've been there for 6 months for no reason (rare, but you'll find cases if you hit Google), and off they go back to the outside population while contagious.

 

The federal system in particular moves people fairly regularly (Remember Con Air? That actually exists.), so it's much harder to test, quarantine, and only vaccinate staff. And the inmate population is both a source of the virus and at risk for the virus if unvaccinated. States typically don't move people as often, and city/county is pretty unusual. And most facilities operate at or above capacity, so I don't know how they're quarantining incoming inmates. Like you, that's thankfully not an area of expertise!

 

So, from a pure public health, disease prevention standpoint, they need vaccinated as early as possible, just like long term care facilities and true nursing care facilities. And college students, etc. Any population that by nature puts a lot of people in close proximity for extended periods of time.

[Ken the cruiser]

The silence is driving me nuts.  No new news on COVID stage 3 vaccine testing in the last few days. No new news on CDC and the No Sail Order. Us for over in the peanut gallery need updates! ☺️☺️

[markeb]

4 minutes ago, Ken the cruiser said:

The silence is driving me nuts.  No new news on COVID stage 3 vaccine testing in the last few days. No new news on CDC and the No Sail Order. Us for over in the peanut gallery need updates! ☺️☺️

Silence is good. Science outside public influence is usually better science. It suggests the regulatory affairs and actual clinical trials folks have temporarily taken over from the PR and finance folks...

[REEtired]

26 minutes ago, Ken the cruiser said:

The silence is driving me nuts.  No new news on COVID stage 3 vaccine testing in the last few days. No new news on CDC and the No Sail Order. Us for over in the peanut gallery need updates! ☺️☺️

🎼 Momma said there’d be days like this 🎼. Driving me nuts as well, but maybe no news is good news. Finger toes arms and eyes crossed.  Any day now !  

[mimbecky]

14 hours ago, Ken the cruiser said:

The silence is driving me nuts.  No new news on COVID stage 3 vaccine testing in the last few days. No new news on CDC and the No Sail Order. Us for over in the peanut gallery need updates! ☺️☺️

 

Well Inovio isn't in phase 3 yet (I don't think) but they are paused now. 

https://markets.businessinsider.com/news/stocks/inovio-stock-price-coronavirus-vaccine-trial-pause-trading-halted-biotech-2020-9-1029626833#

 

Sounds like Pfizer will maybe be the first with hopefully substantial news in about a month.

I'm with you, anxious for play by play.  LOL

 

Great insight about the prison system!

 

M

[markeb]

1 hour ago, mimbecky said:

 

Well Inovio isn't in phase 3 yet (I don't think) but they are paused now. 

https://markets.businessinsider.com/news/stocks/inovio-stock-price-coronavirus-vaccine-trial-pause-trading-halted-biotech-2020-9-1029626833#

 

Sounds like Pfizer will maybe be the first with hopefully substantial news in about a month.

I'm with you, anxious for play by play.  LOL

 

Great insight about the prison system!

 

M

 

Can't find it this morning, but saw either a press release or actual story on this last night. Had to do some looking this morning.

 

Inovio is working on a DNA vaccine. This concept has been around for probably 20 years, but I'm unaware of any being licensed. Naked DNA doesn't get into cells, so historically (and sounds like what Inovio is doing, but their PR is somewhat vague) the DNA that codes for the immunogenic protein was embedded in tiny gold beads, and administered via an electrostatic device that essentially produces an electrostatic charge that momentarily opens up the cells in the deeper layers of the skin to accept the beads and the DNA, which then gets incorporated into protein synthesis in the cell, and bingo, you have SPIKE (in this case). The superficial skin layers are dead cells, so you've got to get it into the living, deeper layers.

 

It looks like the device is in question. I'll confess when I was working vaccine requirements in a previous life, I was never a fan, because there's so much that can go wrong, and you need the device everywhere you're going to administer the vaccine. They seemed to work really well in pre-clinical trials, but the logistics of using them always seemed a bridge too far. Most of the lead candidates in the US now are using novel technologies, which means they're great if all goes well, but they all have potential Achilles heels. The subunit vaccine from Novovax is probably the safest candidate from a regulatory standpoint, but we are just now entering the danger zone on delivering a safe and effective vaccine...

[K.T.B.]

Maybe I missed it, but I found this to be interesting:  https://www.yahoo.com/lifestyle/dr-fauci-says-heres-normality-111021867.html

 

Especially this quote:

 

"I feel cautiously optimistic… given the preliminary data we had in the early phase of the trial and some of the animal studies, that we will have a vaccine that is effective," Fauci told ITV News on Friday.

 

"How effective it is going to be, is totally an open question but we believe we'll have some kind of an effective vaccine by November or December, we're hoping.

 

"But we have to say for honesty and transparency that's not a guarantee, but I think it's a reasonable projection."

 

I'll take that reasonable projection, especially since it's from Fauci.

[cangelmd]

3 hours ago, markeb said:

 

 

It looks like the device is in question. I'll confess when I was working vaccine requirements in a previous life, I was never a fan, because there's so much that can go wrong, and you need the device everywhere you're going to administer the vaccine. They seemed to work really well in pre-clinical trials, but the logistics of using them always seemed a bridge too far. Most of the lead candidates in the US now are using novel technologies, which means they're great if all goes well, but they all have potential Achilles heels. The subunit vaccine from Novovax is probably the safest candidate from a regulatory standpoint, but we are just now entering the danger zone on delivering a safe and effective vaccine...

Markeb, always appreciate your insight and expertise- what do you mean by “entering the danger zone on delivering a safe and effective vaccine”? Just now been long enough to pick up side effects, ADE? Both?.

 

seems 

like it is asking a lot for all these different novel technologies to be successful.

[markeb]

9 minutes ago, cangelmd said:

Markeb, always appreciate your insight and expertise- what do you mean by “entering the danger zone on delivering a safe and effective vaccine”? Just now been long enough to pick up side effects, ADE? Both?.

 

seems 

like it is asking a lot for all these different novel technologies to be successful.

 

I think all of the above, plus anything we haven't thought of yet that could manifest in a large scale clinical trial. Much of what could, but certainly could not, go wrong, could be corrected, but that will take time. 'Danger Zone' was the theme from Top Gun, remember...

 

Yes to your last statement. If any one of them was proven through Phase III and post marketing, I think we'd all be ecstatic at this point, but they haven't been. I'm a huge fan of all the institutes at the NIH (people forget or don't know the I is plural). NCI and NIAID have great track records for basic research, and the line between basic and applied gets pretty blurry at NCI anyway, The old Beltway joke was always that NIH really stood for 'not invented here' and they were big fans of the cutting edge research they either performed or funded. But they were never designed for licensing product, which is one of the big reasons BARDA came online. And BARDA is the actual funding and procurement agency for the US government funded trials as I understand it. At least the big products where the US has committed to procurement.

[TeeRick]

I have personally in my past worked on DNA vaccines.  I am not surprised about the failings of the Inovio DNA vaccine and the gold particle "gene gun" as it is called.  Not really practical (see link below) but if it worked and nothing else did then it would move forward.  DNA vaccines work in animals but not humans.  The West Nile vaccine for horses is a licensed DNA vaccine.

https://en.wikipedia.org/wiki/Gene_gun

 

That is why RNA vaccines (mRNA in lipids)  like the Moderna and Pfizer approaches have surpassed them.  

 

The RNA vaccines are still unproven in humans and there is only the safety data being generated by the current trials.  In normal times it would take a very long time and lots of data for a brand new technology to be approved.  Same can be said for adeno vector vaccines.

 

This is why I hold great hopes for the "turtle" in this race that just entered Phase 3. Novavax.  Also Sanofi/GSK. Traditional protein subunit (SPIKE) in adjuvant.  Lots of clinical data and post-approval data on this type of vaccine.  Very safe.  Hope it works for SARS-CoV-2 and I will line up for it.  In fact I just had my second dose of shingles vaccine this week (Shingrix, GSK) which is Herpes Zoster purified glycoprotein E in adjuvant.  On the market for 10 years now.  Some get a sore arm for a few days but pretty safe and very effective.

 

 

[kelmac]

36 minutes ago, TeeRick said:

In fact I just had my second dose of shingles vaccine this week (Shingrix, GSK) which is Herpes Zoster purified glycoprotein E in adjuvant.  On the market for 10 years now.  Some get a sore arm for a few days but pretty safe and very effective.

 

 

Hi Rick,

I too, got my second Shingrix shot this past Sunday at Walgreens, in addition to my yearly flu shot.  One in the left arm (Shingrix) and the other in my right arm.  Out on the golf course Monday and the left arm hurt a bit and nothing from the flu shot side.  The copay for the shingles shot was $45 and the flu was at no cost to me.  

Enjoying your insight on this subject -- keep it up!  

 

Enjoy!

Kel

[Crazy planning mom]

49 minutes ago, TeeRick said:

I have personally in my past worked on DNA vaccines.  I am not surprised about the failings of the Inovio DNA vaccine and the gold particle "gene gun" as it is called.  Not really practical (see link below) but if it worked and nothing else did then it would move forward.  DNA vaccines work in animals but not humans.  The West Nile vaccine for horses is a licensed DNA vaccine.

https://en.wikipedia.org/wiki/Gene_gun

 

That is why RNA vaccines (mRNA in lipids)  like the Moderna and Pfizer approaches have surpassed them.  

 

The RNA vaccines are still unproven in humans and there is only the safety data being generated by the current trials.  In normal times it would take a very long time and lots of data for a brand new technology to be approved.  Same can be said for adeno vector vaccines.

 

This is why I hold great hopes for the "turtle" in this race that just entered Phase 3. Novavax.  Also Sanofi/GSK. Traditional protein subunit (SPIKE) in adjuvant.  Lots of clinical data and post-approval data on this type of vaccine.  Very safe.  Hope it works for SARS-CoV-2 and I will line up for it.  In fact I just had my second dose of shingles vaccine this week (Shingrix, GSK) which is Herpes Zoster purified glycoprotein E in adjuvant.  On the market for 10 years now.  Some get a sore arm for a few days but pretty safe and very effective.

 

 

So, if the Novavax just started phase 3, would we know if it was effective by Jan/Feb?

[wrk2cruise]

I had the old Shingles vaccine just before Shingrix came out so of course my Dr has been recommending getting the Shingrix version.   It was interesting at my Physical a couple of weeks ago he talked to me about it but said lets put it off a year due to the side effects of fever etc.  He didn't want any symptoms to be confused with covid at this time.   Did get the Flu shot during the visit.

[Covepointcruiser]

I had side effects from the new Shingles (2 injections) but I believe the side effects are mild compared with the disease.    If you look at the news today (NYT), the Moderna vaccine is progressing nicely.    
 

I will be ready to demonstrate if prisoners are given priority over law abiding citizens needing the vaccine.     With some of the current PC opinions those on death row will get it before the rest of us!

[markeb]

34 minutes ago, Covepointcruiser said:

I will be ready to demonstrate if prisoners are given priority over law abiding citizens needing the vaccine.     With some of the current PC opinions those on death row will get it before the rest of us!

 

Not even a rounding error in planning. There were approximately 2603 death row inmates in the US in April. I'd have thought it was higher, but it's not. Either including them or not would be PC as small as the numbers are...

[markeb]

2 hours ago, TeeRick said:

I have personally in my past worked on DNA vaccines.  I am not surprised about the failings of the Inovio DNA vaccine and the gold particle "gene gun" as it is called.  Not really practical (see link below) but if it worked and nothing else did then it would move forward.  DNA vaccines work in animals but not humans.  The West Nile vaccine for horses is a licensed DNA vaccine.

 

Kind of curious what you saw? There's a certain randomness in where the DNA goes, but for a Phase I study to hold up the 2/3, you'd think there were safety concerns. Did the device tend to cause trauma at the injection site? My concerns were always logistics or now having to get both a vaccine and delivery device to every place I needed the vaccine.

 

1/2 inch of dermis in a horse versus millimeters in a human gives a lot of margin of error...

[Porky55]

Don’t seem to have the same aversion to the Covid19 vaccine in the China -

https://www.voanews.com/east-asia-pacific/experts-warn-chinas-emergency-use-covid-19-vaccine
 

[BP99]

21 hours ago, markeb said:

 

Can't find it this morning, but saw either a press release or actual story on this last night. Had to do some looking this morning.

 

Inovio is working on a DNA vaccine. This concept has been around for probably 20 years, but I'm unaware of any being licensed. Naked DNA doesn't get into cells, so historically (and sounds like what Inovio is doing, but their PR is somewhat vague) the DNA that codes for the immunogenic protein was embedded in tiny gold beads, and administered via an electrostatic device that essentially produces an electrostatic charge that momentarily opens up the cells in the deeper layers of the skin to accept the beads and the DNA, which then gets incorporated into protein synthesis in the cell, and bingo, you have SPIKE (in this case). The superficial skin layers are dead cells, so you've got to get it into the living, deeper layers.

 

It looks like the device is in question. I'll confess when I was working vaccine requirements in a previous life, I was never a fan, because there's so much that can go wrong, and you need the device everywhere you're going to administer the vaccine. They seemed to work really well in pre-clinical trials, but the logistics of using them always seemed a bridge too far. Most of the lead candidates in the US now are using novel technologies, which means they're great if all goes well, but they all have potential Achilles heels. The subunit vaccine from Novovax is probably the safest candidate from a regulatory standpoint, but we are just now entering the danger zone on delivering a safe and effective vaccine...

Hi,

The pause for Inovio "may" be the device BUT they also have had lots of bad

press lately about lawsuits due to manufacturing (a change) and information

to shareholders. Do a google with "Inovio and lawsuits".

[TeeRick]

12 hours ago, markeb said:

 

Kind of curious what you saw? There's a certain randomness in where the DNA goes, but for a Phase I study to hold up the 2/3, you'd think there were safety concerns. Did the device tend to cause trauma at the injection site? My concerns were always logistics or now having to get both a vaccine and delivery device to every place I needed the vaccine.

 

1/2 inch of dermis in a horse versus millimeters in a human gives a lot of margin of error...

The simple DNA vaccines (delivered by im injection with or without lipids) always worked in pre-clinical animal models, even monkeys.  The gene gun was not really needed and the horse West Nile vaccine in fact does not use it.  The gene gun logistics would be a formidable hurdle for a worldwide vaccine in any scenario.  But immune responses in human clinical trials with DNA vaccines are spotty at best.  And some still worry about DNA integration into the genome of cells once injected but to my knowledge this has never been seen.

 

But it appears according to Inovio that their trial pause was due to FDA questions about their Cellectra 2000 delivery device which is an electroporation (patch with electrodes) delivery and not gene gun delivery.  The patch is more complicated than a needle but can be adapted to more widespread use than the gold particle gene gun.

https://www.clinicaltrialsarena.com/news/fda-holds-inovio-vaccine-trial/

Edited September 30, 2020 by TeeRick

[Doris&Nereus]

What do you think about this article on an antibody therapy that could be of tremendous help? I know that I posted about this before, but I just don't see why we can't

expand our efforts to include more therapies. We should not put all our eggs in one basket, INMHO.

 

https://www.washingtonexaminer.com/opinion/op-eds/an-antibody-therapy-could-get-us-to-the-new-normal

[BP99]

2 hours ago, Doris&Nereus said:

What do you think about this article on an antibody therapy that could be of tremendous help? I know that I posted about this before, but I just don't see why we can't

expand our efforts to include more therapies. We should not put all our eggs in one basket, INMHO.

 

https://www.washingtonexaminer.com/opinion/op-eds/an-antibody-therapy-could-get-us-to-the-new-normal

Hi,

I think that the monoclonal antibody therapy is a great approach to treating

patients with covid. However (IMO), all FDA approved monoclonals for

other diseases (eg. cancer) are outrageously expensive. They are expensive

to produce and deliver. To be used as a preventative would be costly

(unlike most vaccines).

 

[BP99]

3 hours ago, BP99 said:

Hi,

I think that the monoclonal antibody therapy is a great approach to treating

patients with covid. However (IMO), all FDA approved monoclonals for

other diseases (eg. cancer) are outrageously expensive. They are expensive

to produce and deliver. To be used as a preventative would be costly

(unlike most vaccines).

 

To further add numbers:

There have been 7,500,000 infected with covid in the USA (total).

Usually 1 in 5 requires hospitalization (1,500,000).

The "average" cost for "other" monoclonal treatment ~ $100,000

(but usually ~ $250,000 for annual cancer treatment).

To treat all early covid hospital cases (which is recommend with

the monoclonals) would cost $150,000,000,000. YES, I think

this cost is worth paying to save 100's of thousands of lives!

The companies who make these monoclonals may decrease

the cost for this pandemic but I haven't seen anything on this.

All the numbers I obtained are guestamations and may not

be correct. My examples are at the "high" end. Hopefully

the cost will be reasonable so that no further deaths happen

during treatment of patients.

 

 

 

[TeeRick]

I agree with BP99 here.  Ab therapy is just that - a therapy for COVID patients.  Not an alternative to the billions of doses needed for a worldwide vaccine.