Are vaccines the light at the end of the tunnel?

[Ken the cruiser]

Hey, I just want to thank everyone who has contributed to this thread over these past several months. Yes, there have definitely been some interesting perspectives shared on this thread. But at the same time I've always been amazed how some of our more insightful contributors have stepped up with some very meaningful responses to bring the stress level back down, as this has definitely been some very dark times we've all been going through together.

 

And I know we're not there yet, but with the pending approval of the "one shot" J&J vaccine to go along with the massive ramping up of the production lines associated with the Pfizer and Moderna vaccines, that light keeps getting brighter and brighter.

 

Now, will the cruise lines get a temporary PVSA waiver so Alaska might open up to cruise ships this coming season? Probably not. But, I'm starting to see a glimmer of hope that we may be able to go on some short Caribbean cruises this summer. Of course, that's all up to the CDC and I'm just sitting over here in the peanut gallery. But it does feel like we've past the apex of this very dark ride and the light does seem to be getting a little brighter and brighter every day. 🙃

[markeb]

Generally speaking, they're going to have to take their clinical trial to completion and file a complete BLA. Most of those trials run late into this year or through 2022. They're all doing rolling submissions on fast track, so there's a possibility that at some point they'll either suggest to the FDA they have enough data, or the FDA will suggest to them they have enough data. Not my area of experience, although there are a few people on this thread who have worked those programs as regulators.

 

With rolling submissions and continued data analysis, it theoretically wouldn't be long after filing a complete BLA (Biological License Application) to receive approval. There's also a probability that as incidence of disease drops, you'll lose statistical power for more studies, and ideally you won't have enough disease for more trials. They should be collecting a ton of what would normally be post-marketing and/or Phase IV data now.

[TeeRick]

23 minutes ago, markeb said:

With what looks like a high probability of approval of an EUA for J&J, possibly as early as this weekend, and the already approved  Pfizer and Moderna vaccines, some random, hopefully not too technical thoughts, on what's next in the US.

 

First, if J&J meets most of its delivery targets, and Pfizer and Moderna stay on track, they will arguably produce enough vaccine to meet US needs. Absent an unmet need, I personally think these are the three EUAs for the US. That doesn't mean that Novavax, for instance, can't go through a full clinical trial and submit a full BLA for licensure in 2-3 years, but the way the law is written, you need an unmet medical need for an EUA. My only caveat on a subunit vaccine like Novavax is if it ultimately appears "safer" in some population. But the safety profiles on these novel vaccines have been very good to excellent so far.

 

What about variants? These three have made it to a point that the FDA appears willing to allow them to bridge their previous safety and efficacy trials to new antigens produced basically under the same methodology. So the two mRNA candidates can produce additional mRNA for different SPIKE configurations, perform small scale clinical trials, and go back for amendment to their previous filings. Same for J&J. I don't know if that will extend to two or more mRNA or vectored vaccines in the same vial, and what will be necessary for that modification; there's guidance out, but I haven't looked for that level of detail.

 

IMHO, that means that AZ is not going to get an emergency approval in the US, and it may well have to modify antigens and repeat trials. I don't know if the FDA guidance would allow bridging in the US as I don't believe they have a filing for approval here. European authorities may allow them to change antigens and bridge.

 

I will be the first to admit that when this thread started in July, I was more than a little skeptical that we'd be where we are this week. Especially with what everyone thought was the lead horse coming up lame on the backstretch. For those of you who've not witnessed up close the perils and pitfalls of vaccine development, this is a miracle.

Novavax is definitely in the mix for an EUA.  And I believe so is AZ/Oxford.  Both are completing large Phase 3 studies in the US.  Novavax is a traditional subunit technology so it might be used for maybe people with allergic reactions to mRNA vaccines?  AZ/Oxford Adeno might be compared to J&J for similarities and differences for an EUA to be approved.  But all of the doses count!  We want them all I think!

https://www.dailymail.co.uk/health/article-9286595/Novavax-completes-enrollment-U-S-trial-COVID-19-vaccine.html

 

https://www.businessinsider.com/when-will-astrazeneca-covid-vaccine-be-approved-in-us-2021-1

 

[TeeRick]

36 minutes ago, mimbecky said:

I have heard a few people say they won't take the vaccine as long as it has only an EUA. 

Any idea when any of them would have full approval? 

I personally think it is an excuse but maybe that would make a difference for some people.

 

These are people who really do not understand the process I think.

[Ken the cruiser]

I have to admit the weekly production estimates of that many vaccine doses just staggers my mind. I love it!

 

U.S. poised to have 3M vaccine doses available per day by April (yahoo.com)

[cangelmd]

Do you think J and J will be recommended for everyone, or just some groups, particularly younger people?

[mimbecky]

1 hour ago, TeeRick said:

These are people who really do not understand the process I think.

Of course not, but neither do I.

However I  must be more trusting because I’m just waiting for my delayed 2nd dose and am thrilled to get it soon 🤞🏼💪🏼
Just wondering when I might stop hearing the mantra “it’s not even fully approved” . Of course there will always be an excuse.

[Fouremco]

1 hour ago, Ken the cruiser said:

 

Now, will the cruise lines get a temporary PVSA waiver so Alaska might open up to cruise ships this coming season? Probably not. But, I'm starting to see a glimmer of hope that we may be able to go on some short Caribbean cruises this summer.

Bermuda and most Caribbean islands are opening up to visitors, but with strict health protocols. https://www.travelweekly.com/Caribbean-Travel/Caribbean-readies-for-a-wave-of-reopenings

 

I certainly hope that the cruise lines and CDC can come to an agreement on COVID-related health requirements, and that these protocols are subsequently deemed sufficient by the Caribbean nations for them to make exceptions for cruise passengers. 

 

🤞

[cruisemom42]

2 hours ago, markeb said:

I will be the first to admit that when this thread started in July, I was more than a little skeptical that we'd be where we are this week. Especially with what everyone thought was the lead horse coming up lame on the backstretch. For those of you who've not witnessed up close the perils and pitfalls of vaccine development, this is a miracle.

 

Amen to that.

 

As someone who has worked in the pharma industry, it is both amazing and gratifying to see what has been done. Six months ago most posts on CC on this topic were saying there is no way we'd have a vaccine in a year, nevermind three and over 1.88 million doses given so far in the US alone.

[SeaHunt]

I posted this on the RCI board but thought if you haven't already read it you might like to see it too 😊

 

Crew-center has an interesting article about crew vaccinations that includes this tidbit:

 

"According to the Chairman of the Indonesian Seafarers' Union (KPI) Bali I Dewa Putu Susila, 6,000 crew members in Bali are waiting to board the cruise ships in April".

 

http://crew-center.com/latest-insights-about-covid-vaccination-crew

[Arizona Wildcat]

1 hour ago, cangelmd said:

Do you think J and J will be recommended for everyone, or just some groups, particularly younger people?

J&J was tested on 18+.  Any comments welcome on permission processes for under 18 and those not capable of granting permission.

 

Am guessing getting approvals from parents or guardians for "children" would be often difficult.  Similar to issues locally in getting permission to vaccinate many in memory care units.

[Charles4515]

17 minutes ago, SeaHunt said:

I posted this on the RCI board but thought if you haven't already read it you might like to see it too 😊

 

Crew-center has an interesting article about crew vaccinations that includes this tidbit:

 

"According to the Chairman of the Indonesian Seafarers' Union (KPI) Bali I Dewa Putu Susila, 6,000 crew members in Bali are waiting to board the cruise ships in April".

 

http://crew-center.com/latest-insights-about-covid-vaccination-crew

 

They could be waiting in May. Or June. Or July. Or August....etc.

[TeeRick]

1 hour ago, mimbecky said:

Of course not, but neither do I.

However I  must be more trusting because I’m just waiting for my delayed 2nd dose and am thrilled to get it soon 🤞🏼💪🏼
Just wondering when I might stop hearing the mantra “it’s not even fully approved” . Of course there will always be an excuse.

Over 65 million doses in the US and counting as of today.  Not many issues reported.  This is better than a phase 3 trial - producing safety and efficacy data post EUA.  Not sure what more evidence people need to get vaccinated but I sure wish I could get an appointment!

[nocl]

7 hours ago, TeeRick said:

I agree that this is the elephant in the room right now.  The more transmissible versions of the virus (like UK variant for example) have been out there for awhile.  Even before a lot of vaccinations in the UK happened.  But could it morph into something else in vaccinated people?  Maybe so but can it get a true resistance against vaccine polyclonal antibody responses and T-cell responses?  And to become actually more deadly?  Or will it cause mild to moderate Covid only? 

 

I am definitely a bit concerned as anything can happen.  But not overly concerned at this point in time.  If a new vaccine-resistant variant arises, the current vaccine technology can be applied pretty quickly to match it.  The new vaccine can be tested quickly now according to FDA (and other regulatory agencies will likely follow).  It can be used as a booster in those vaccinated or as the primary vaccine in those not yet vaccinated.  Or mixed in a vial together.  Or prime boost.  A lot of options.  Science and medicine will get this little viral bugger!

The question is not so much can it mutate inside vaccinated people as it is that with the vaccine reducing the less infectious strains can a mutation that is vaccine resistant get a foot hold  if people stop doing the other prevention elements.

 

It turns out that California has a home grown more infectious strain (might account for the recent CA case numbers) and they have a case where one person got both it and the UK strain at the same time which has now created a third strain (the two viruses exchanged DNA)

 

Oh eventually we will get ahead if we do not lose patience.

[nocl]

30 minutes ago, Arizona Wildcat said:

J&J was tested on 18+.  Any comments welcome on permission processes for under 18 and those not capable of granting permission.

 

Am guessing getting approvals from parents or guardians for "children" would be often difficult.  Similar to issues locally in getting permission to vaccinate many in memory care units.

The under 18 trials will be much smaller trials, more focused on safety and equivalence than the original phase three trials.  They will still take time.

 

In the meantime anybody that vaccinates someone under the age listed on the product label is doing so off label and assuming risk if anything goes wrong.

[nocl]

2 hours ago, TeeRick said:

Novavax is definitely in the mix for an EUA.  And I believe so is AZ/Oxford.  Both are completing large Phase 3 studies in the US.  Novavax is a traditional subunit technology so it might be used for maybe people with allergic reactions to mRNA vaccines?  AZ/Oxford Adeno might be compared to J&J for similarities and differences for an EUA to be approved.  But all of the doses count!  We want them all I think!

https://www.dailymail.co.uk/health/article-9286595/Novavax-completes-enrollment-U-S-trial-COVID-19-vaccine.html

 

https://www.businessinsider.com/when-will-astrazeneca-covid-vaccine-be-approved-in-us-2021-1

 

With AZ it all depends upon their US trials.  Their original trials were a mess from both the demographics as well as the varying trial protocols.

 

The SA data does not help them since J&J had better results against that variant.

 

In a few months the US will have a vaccine glut.  I expect by early summer it will be a just go to your local pharmacy.

[Ken the cruiser]

14 minutes ago, TeeRick said:

Over 65 million doses in the US and counting as of today.  Not many issues reported.  This is better than a phase 3 trial - producing safety and efficacy data post EUA.  Not sure what more evidence people need to get vaccinated but I sure wish I could get an appointment!

Rick, are you by chance a military veteran? If so, this was just posted Feb 23rd on our local VA's FB page where veterans 55 and older can get a vaccine. You may want to see if there is one in your area offering similar walk-in services. NOTE: If not currently enrolled in the VA, it takes about 2 minutes to do so once you get there.

 

(2) Central Alabama Veterans Health Care System | Facebook

 

 

Edited February 24, 2021 by Ken the cruiser

[nocl]

4 hours ago, markeb said:

FDA professional staff view the J&J vaccine candidate as safe and effective and are recommending an EUA ahead of the advisory committee meeting on Friday.

 

From the WAPO (should be a free article for now). https://www.washingtonpost.com/health/2021/02/24/johnson-and-johnson-vaccine/

 

Some concerns noted as to public perception due to somewhat lower efficacy numbers, but these trials occurred with the circulation of some of the variants, and still had great results against the most significant disease outcomes.

If they are smart they would route the J&J vaccines to the more rural areas that have had issues with the storage requirements for Moderna and Pfizer.  Areas where it is more difficult to coordinate the second shot. Areas that also tend to be a bit lower risk than more dense urban areas.

[markeb]

8 minutes ago, nocl said:

If they are smart they would route the J&J vaccines to the more rural areas that have had issues with the storage requirements for Moderna and Pfizer.  Areas where it is more difficult to coordinate the second shot. Areas that also tend to be a bit lower risk than more dense urban areas.

 

From a purely medical/public health point of view, that makes a lot of sense. From a public perception point of view, with the lower reported efficacy (even though all the vaccines' real world performance is probably too similar to really differentiate), I don't think you can do that. And when you look at the CDC reports, some of the best vaccine rates in the country are in some of the more rural states. They don't break that down by county, but it's been a trend for a while now.

[deadzone1003]

4 hours ago, Ken the cruiser said:

I have to admit the weekly production estimates of that many vaccine doses just staggers my mind. I love it!

 

U.S. poised to have 3M vaccine doses available per day by April (yahoo.com)

Pfizer and Moderna have to distribute at a rate of 3,000,000 doses a day just to make their March 31st contractual obligation of 100,000,000 doses for each company.  If J&J is approved this Friday, we should be past 3,000,000 a day in March.  This is assuming the companies are not having production difficulties, though J&J seems to have some.   One good sign is there was a big jump in distribution in the last few days which I hope is a sign of what is coming.  

[lyndarra]

10 hours ago, TeeRick said:

I agree that this is the elephant in the room right now.  The more transmissible versions of the virus (like UK variant for example) have been out there for awhile.  Even before a lot of vaccinations in the UK happened.  But could it morph into something else in vaccinated people?  Maybe so but can it get a true resistance against vaccine polyclonal antibody responses and T-cell responses?  And to become actually more deadly?  Or will it cause mild to moderate Covid only? 

 

I am definitely a bit concerned as anything can happen.  But not overly concerned at this point in time.  If a new vaccine-resistant variant arises, the current vaccine technology can be applied pretty quickly to match it.  The new vaccine can be tested quickly now according to FDA (and other regulatory agencies will likely follow).  It can be used as a booster in those vaccinated or as the primary vaccine in those not yet vaccinated.  Or mixed in a vial together.  Or prime boost.  A lot of options.  Science and medicine will get this little viral bugger!

I believe your concern is justified.

Of concern to me atm is the massive buy-up of vaccine by rich countries to the detriment of the poor. Unless more assistance is given to poorer countries the virus is free to carry on its merry way mutating into who knows what.

[d9704011]

5 minutes ago, lyndarra said:

I believe your concern is justified.

Of concern to me atm is the massive buy-up of vaccine by rich countries to the detriment of the poor. Unless more assistance is given to poorer countries the virus is free to carry on its merry way mutating into who knows what.

The picture on vaccine for poorer countries isn’t entirely dark.  Look up the recent story on vaccines for Ghana through COVAX.

[lyndarra]

1 minute ago, d9704011 said:

The picture on vaccine for poorer countries isn’t entirely dark.  Look up the recent story on vaccines for Ghana through COVAX.

Thank you. I am aware of COVAX. Also, it was good to see that the US had rejoined WHO.

[nocl]

2 minutes ago, d9704011 said:

The picture on vaccine for poorer countries isn’t entirely dark.  Look up the recent story on vaccines for Ghana through COVAX.

Not entirely dark but to put things in perspective the US is 340 million, the EU is 447 million. So the developed countries maybe one billion.  China, Russia and the rest of the world 6.8 billion.  At best, even if the vaccines are free it is going to take quite a while.

 

 

[d9704011]

3 minutes ago, nocl said:

Not entirely dark but to put things in perspective the US is 340 million, the EU is 447 million. So the developed countries maybe one billion.  China, Russia and the rest of the world 6.8 billion.  At best, even if the vaccines are free it is going to take quite a while.

 

 

Thanks for the transmutation of a little bit of good news into a lump of coal.