PlagueWatch 2020-23 - Coronavirus

[MarkD83]

Have not been to this thread in awhile so I hope this is not old news.

https://www.cbsnews.com/news/covid-1...ion-doses-day/

"The Centers for Disease Control and Prevention on Wednesday reported that more than 951,000 doses of the vaccine had been administered to people around the country. That is by far the fastest daily pace of vaccinations since the rollout started a month ago and a big jump from the previous day, when just under 340,000 doses were given."

[Mike Corey]

Love that pace picking up speed!

[Mike Corey]

Hey experts. This seems promising from J&J.

[budwom]

Hey experts. This seems promising from J&J.

I know someone there, and they're keen on their vaccine, though they've had a manufacturing hiccup...they do have massive mfg capacity is they can straighten that out.

[tbyers11]

Hey experts. This seems promising from J&J.

Yes, good news. Just looked at the NEJM link you posted.

Neutralizing Ab titers after one dose look pretty strong. Far better than either mRNA vaccine after the first dose. Makes the case that one shot might be enough for this vaccine. Have to wait for efficacy to confirm because as the authors correctly state we don't really know what a "good enough" level of nAb is yet. Although the authors state that the immune response in 65 older group was "modestly lower' after one shot than the youngsters they look pretty similar to me. T cell data looks good. Strong and the right type of CD4 and strong CD8 response.

I am confused why they enrolled the 65 and older cohort 2 months after the 18-55 cohort which means we don't have post second shot data for the 65+ yet. But that is coming and it appears both 18-55 and 65+ are studied in the both one shot and 2 shot cohort for the ongoing Ph3 efficacy trials. As I assume their one shot Ph3 study is the one that will finish first (their Ph3 2 dose regimen gives 2nd dose 57 day after the first) and is being touted for potential EUA in February this is promising for a 3rd vaccine in the US.

[CDu]

Yes, good news. Just looked at the NEJM link you posted.

Neutralizing Ab titers after one dose look pretty strong. Far better than either mRNA vaccine after the first dose. Makes the case that one shot might be enough for this vaccine. Have to wait for efficacy to confirm because as the authors correctly state we don't really know what a "good enough" level of nAb is yet. Although the authors state that the immune response in 65 older group was "modestly lower' after one shot than the youngsters they look pretty similar to me. T cell data looks good. Strong and the right type of CD4 and strong CD8 response.

I am confused why they enrolled the 65 and older cohort 2 months after the 18-55 cohort which means we don't have post second shot data for the 65+ yet. But that is coming and it appears both 18-55 and 65+ are studied in the both one shot and 2 shot cohort for the ongoing Ph3 efficacy trials. As I assume their one shot Ph3 study is the one that will finish first (their Ph3 2 dose regimen gives 2nd dose 57 day after the first) and is being touted for potential EUA in February this is promising for a 3rd vaccine in the US.

Yes, the JnJ vaccine appears likely to be approved next month and the AstraZeneca vaccine is targeting late-March. Hopefully the results for each will be good and we'll have 4 options available in the Spring.

Of course, just as importantly is the rollout and administration. Right now we still have about 20 million doses that haven't been administered out of the ~30 million that were delivered. It won't matter much if we have a ton of doses if those doses aren't efficiently getting into people's arms.

[tbyers11]

Yes, the JnJ vaccine appears likely to be approved next month and the AstraZeneca vaccine is targeting late-March. Hopefully the results for each will be good and we'll have 4 options available in the Spring.

Of course, just as importantly is the rollout and administration. Right now we still have about 20 million doses that haven't been administered out of the ~30 million that were delivered. It won't matter much if we have a ton of doses if those doses aren't efficiently getting into people's arms.

Agree on rollout and shots in arms. Even if JnJ has a 2 month delay it is not going to matter if they don't have a huge amount of doses in February because we will not have administered all the Moderna and Pfizer that we have.

If they can catch up by April hopefully we have a more robust vaccination program in place to take advantage of lots of JnJ doses (and any potential issues that might crop up with Moderna or Pfizer manufacturing).

[CDu]

Agree on rollout and shots in arms. Even if JnJ has a 2 month delay it is not going to matter if they don't have a huge amount of doses in February because we will not have administered all the Moderna and Pfizer that we have.

If they can catch up by April hopefully we have a more robust vaccination program in place to take advantage of lots of JnJ doses (and any potential issues that might crop up with Moderna or Pfizer manufacturing).

Yep, that is the key. We need to get our rollout to the point where we can handle 2+ million doses administered per day. It doesn’t do much good to get 40+ million doses per month if we are only administering at half that pace.

[rsvman]

Hey experts. This seems promising from J&J.

With the caveat that this study is only looking at adverse effects and antibody production, I agree that the data look pretty good. Antibody levels will likely correlate with efficacy, but this study is not equivalent to the ones done by Pfizer and Moderna that actually looked at Covid-19 in vaccine recipients versus placebo recipients.

I don't know anything about the specific adenovirus vector that they used to make the vaccine, and that information is not in the article, as it was only addressing safety and immunogenicity (I'm sure they have published a paper earlier about their vector and how they produced the vaccine, but I haven't read it). Generally speaking, I like the idea of the mRNA vaccine better than a vectored vaccine, but without knowing more specifics about it, I don't want to opine further.

For the uninitiated, the way a vectored vaccine works is generally like this: 1) you make a plasmid (essentially circular genetic material) and insert it into a replication-competent virus, 2) you infect the animal with the virus. The idea is that when the virus infects the cells, it begins to produce the protein that the plasmid encodes (in this case, the S protein of SARS-CoV-2), which allows the body to make an immune response to it.

Adenoviruses are so named because they were found deep in adenoid tissue that had been surgically removed. In addition to acute, rapidly self-resolving infections, adenoviruses can also produce more long-lasting, low-level replication infections in tissues like tonsils and adenoids.

One concept of vectored vaccines would be to have the vector replicate briefly and then either shut itself down or have it be shut down in some way. This is sometimes accomplished by using a virus that doesn't replicate very well in the tissues into which it is introduced, often because said tissues are not in its host range. For example, we could use a fowlpox virus as a vector. The fowlpox virus is optimized to replicate in fowl, so in humans, after a brief period of successful replication (ideally just long enough to produce enough antigen to stimulate an antibody response), the virus shuts itself down (more precisely, it is unable to continue replicating). Such a vaccine would work in a very similar way to an mRNA vaccine (because mRNA is broken down by RNases in the body after a brief period of time).

Another thing about vectored vaccines that I don't particularly like is that your body might also make an immune response directed at the vector. Would this shut it down too soon? Would it make it harder to get a good response the next time vaccination is required? Perhaps on the plus side, maybe the vectored vaccine would produce a more durable response if it replicates a bit longer than mRNA would be expected to survive? Another plus of vectored vaccines is that they don't require adjuvants and that they tend to produce good cytotoxic T-cell responses in addition to antibody responses. I am certain that since the last time I thought seriously about vectored vaccines they have come a long way; specifically, the vector could be genetically altered to "program it" to replicate a certain amount, perhaps to take away some of its own immunogenicity, and to prevent side effects.

I am not really an expert in vectored vaccines, and, as I mentioned, I don't really know much about the adenovirus vector they are using (like what its host range is, etc).

I am typing this response off the top of my head; very busy at work today and do not have time to actually review the preclinical data. Adenoviruses are DNA viruses, and my area of expertise is really RNA viruses. All this is to say please don't take any of these ramblings as gospel. In all likelihood they have chosen a great vector, genetically modified it to produce the amount of replication they want, and to be very safe. It is also likely that the immunogenicity (antibody) responses they published will translate into excellent protection. It may also generate a broader immune response, which might make it work even better.

Final disclaimer: still fighting off the last of the extreme sleepiness that the second vaccine gave me; my response may ramble a bit because of this persistent "brain fog."

[dudog84]

Yes, good news. Just looked at the NEJM link you posted.

Neutralizing Ab titers after one dose look pretty strong. Far better than either mRNA vaccine after the first dose. Makes the case that one shot might be enough for this vaccine. Have to wait for efficacy to confirm because as the authors correctly state we don't really know what a "good enough" level of nAb is yet. Although the authors state that the immune response in 65 older group was "modestly lower' after one shot than the youngsters they look pretty similar to me. T cell data looks good. Strong and the right type of CD4 and strong CD8 response.

I am confused why they enrolled the 65 and older cohort 2 months after the 18-55 cohort which means we don't have post second shot data for the 65+ yet. But that is coming and it appears both 18-55 and 65+ are studied in the both one shot and 2 shot cohort for the ongoing Ph3 efficacy trials. As I assume their one shot Ph3 study is the one that will finish first (their Ph3 2 dose regimen gives 2nd dose 57 day after the first) and is being touted for potential EUA in February this is promising for a 3rd vaccine in the US.

Am I wrong to be bothered that my cohort (I assume cohort 2 was age 56 to 64) was not included?

[Tooold]

.....
Final disclaimer: still fighting off the last of the extreme sleepiness that the second vaccine gave me; my response may ramble a bit because of this persistent "brain fog."

Thanks for all this information! I understand most of what you wrote, and I appreciate your insight!

[tbyers11]

Am I wrong to be bothered that my cohort (I assume cohort 2 was age 56 to 64) was not included?

According to the Supplementary Index, cohort 2 doesn't appear to be the missing 56-64 age group, but is a different cohort that is going to be longer term study looking at effects of booster vaccinations at 6, 12, and 24 months.

You should be slightly bothered that your 56-64 age cohort was not included. There is evidence (including studies I have worked on) that shows immune response to vaccinations begins to wane a fair amount around 50-55 rather than as was previously thought to occur at 65. High dose flu trials were done with 65 as the age cutoff for example.

So I think JnJ set their high age cutoff in the "regular" adult group at 55 rather than 64 to try and make their "regular" adult cohort potentially look better if their vaccine produced markedly weaker immunogenicity in the 65+ group. Good news is that their 65+ data looks very similar to 18-55 to date.

Does bring up the interesting question though, that if their 65+ data looked much worse that their regular adult (18-55) group would the vaccine be licensed (or given EUA) for only those 55 and under?

[Lord Ash]

Dammit, I love DBR.

[LasVegas]

In Vegas, if I become a smoker I can jump a whole group ahead of where I am at now. Any recommendations on cigarettes?

[CrazyNotCrazie]

In Vegas, if I become a smoker I can jump a whole group ahead of where I am at now. Any recommendations on cigarettes?

I believe New Jersey did the same thing, putting them ahead of teachers. I believe their rationale is that the CDC said that smokers are at higher risk, though I don't think the CDC said this means they should move up in the line. How do you prove you are a smoker, thus allowing you to go to the front of the line?

[rsvman]

In Vegas, if I become a smoker I can jump a whole group ahead of where I am at now. Any recommendations on cigarettes?

LOL. I don't really know. I understand that they might be bad for your health.

[JasonEvans]

I believe New Jersey did the same thing, putting them ahead of teachers. I believe their rationale is that the CDC said that smokers are at higher risk, though I don't think the CDC said this means they should move up in the line. How do you prove you are a smoker, thus allowing you to go to the front of the line?

Live picture of my wife after reading this post...

[CrazyNotCrazie]

Live picture of my wife after reading this post...

Yup. I live about three miles from NJ as the crow flies (with a river in between) - if I started walking now, I could easily be there for dinner. Mrs. CNC has a chronic condition that likely qualifies her in NJ but not yet in NY. And if it doesn't qualify her in NJ, she is happy to have a cigarette to qualify (I believe the first one she has ever smoked).

[sparv]

Yes, the JnJ vaccine appears likely to be approved next month and the AstraZeneca vaccine is targeting late-March. Hopefully the results for each will be good and we'll have 4 options available in the Spring.

Of course, just as importantly is the rollout and administration. Right now we still have about 20 million doses that haven't been administered out of the ~30 million that were delivered. It won't matter much if we have a ton of doses if those doses aren't efficiently getting into people's arms.

Has anyone heard explanations for the holdup? It shouldn't be a storage issue, as the vaccines are already stored once distributed. It certainly doesn't seem to be a demand issue, as plenty of people want the vaccine.

Is it a shortage of people to administer the vaccine? If it is intramuscular (which it looks like to my untrained eye), couldn't people be recruited and trained? Anyone who has done IVF, takes a dermato-biologic, heck - even anabolic steroid users -- already knows how to give an IM shot. Maybe the issue is space? Open up more convention centers, sports arenas, etc that are sitting empty anyway.

Texas has administered less than 60% of the vaccines it has, even weeks after the governor said that no vaccines would be held back.

[aimo]

Has anyone heard explanations for the holdup? It shouldn't be a storage issue, as the vaccines are already stored once distributed. It certainly doesn't seem to be a demand issue, as plenty of people want the vaccine.

Is it a shortage of people to administer the vaccine? If it is intramuscular (which it looks like to my untrained eye), couldn't people be recruited and trained? Anyone who has done IVF, takes a dermato-biologic, heck - even anabolic steroid users -- already knows how to give an IM shot. Maybe the issue is space? Open up more convention centers, sports arenas, etc that are sitting empty anyway.

Texas has administered less than 60% of the vaccines it has, even weeks after the governor said that no vaccines would be held back.

Yes, it is intramuscular. That's why most people are experiencing the arm pain. Where I work, they are requesting more vaccine, they are ready to get people in, but they are not getting consistent enough info on how many doses they're getting and when in order to schedule people accordingly. Very frustrating.

I think once facilities get their logistics figured out (ie, finding enough staff to prepare the vaccines, vaccinate, check in, etc, out of the remaining folks who aren't already testing people, taking care of COVID patients, or out sick themselves) they will be able to set up "blitzes" where they can vaccinate thousands in a day at one site. It is starting slow but I imagine (and hope) it will pick up and catch up quickly.