COVID-19: Vaccine/antidote and testing procedures Megathread [Mod Warning - Post #1]

tobefrank321 · 03-09-2020 11:11AM

Any vaccine would have to work on the elderly and those most at risk.

If it doesn't, its easy to foresee a situation where a large percentage of the healthy population refuse to get the vaccine for various reasons. This would leave the elderly open to infection or almost as bad in permanent fear of meeting the wrong person who isn't vaccinated.

I'm not sure how extensive trials have been of potential vaccines on the elderly and those with weakened immune systems so far.

Cordell · 03-09-2020 11:27AM

I think the vaccine must be prioritized for those that can break the transmission chain (like teachers and health workers) rather than those most at risk.

ddarcy · 03-09-2020 11:40AM

tobefrank321 wrote: »

Any vaccine would have to work on the elderly and those most at risk.

If it doesn't, its easy to foresee a situation where a large percentage of the healthy population refuse to get the vaccine for various reasons. This would leave the elderly open to infection or almost as bad in permanent fear of meeting the wrong person who isn't vaccinated.

I'm not sure how extensive trials have been of potential vaccines on the elderly and those with weakened immune systems so far.

Phase III is where this occurs. So more diverse groups are tested. If initial results on a healthy population are meeting expectations then it’s rolled out to more high risk groups. The patients are flagged in the beginning for this.

And it’s not talked about much but there is also a Phase IV. The drug is approved for use after III but only gets the official nod after IV. This is when you see really abstract interactions with the drug. So it needs to be evaluated from a safety standpoint on the rollout as well. If you’re not on any other medications there are almost always no risks, but if you have a combination of insulin/ birth control/ blood pressure/ pain meds, etc then there could be an issue, but these are very rare areas to test.

Phase IV is like a mortgage. Phase III is approval and you get the house. Phase IV is you paying it back and meeting all the criteria Of the mortgage. You stop paying it back you lose the house (except for Ireland, but that’s a different story!). The same goes with medicine if on full launch more issues are seen, it could be pulled or more restrictions put onto it. If this occurs most pharma companies will investigates why and go through trials ago with an altered drug that don’t have these adverse events.

tobefrank321 · 03-09-2020 11:58AM

Cordell wrote: »

I think the vaccine must be prioritized for those that can break the transmission chain (like teachers and health workers) rather than those most at risk.

That seems to be the plan in most countries, but again, can you force teachers and healthcare workers to take the vaccine? What are the penalties if some refuse? Even one or two non vaccinated pose a risk if they come into contact with someone infected elsewhere.

Cordell · 03-09-2020 12:12PM

No, you can't really force them (but you can advise them that the refusal may be taken into the account in the future for various purposes including promotions and redundancies), but I expect 90% or even more in case of health workers will take it voluntarily and this will be a big improvements.
The risk and transmission will never be zero, so bringing them as low as possible will be the goal.

iguana · 03-09-2020 12:21PM

tobefrank321 wrote: »

Any vaccine would have to work on the elderly and those most at risk.

Our immune systems wane as we age, so it's usual that elderly people do not have as strong an immune response from vaccines. (The same is true for people with various immune deficiencies.) There isn't a whole lot we can do about that except ensure that as many healthy people as possible vaccinate. Vaccines work by nearly whole populations having a degree of immunity. They simply can't be designed to protect the most vulnerable if the rest of us are swanning around the place potentially passing on infections.

It's why attempts to sway anti-vax people by telling them that they are endangering their children won't work. They probably aren't. Most of them will have had the standard childhood illnesses themselves and know that for the majority they are fine. Making the reality clear that you and your healthy children are protecting others who are not so lucky, would probably be better a way forward. Vaccination is so often an act of kindness and caring. Vaccination makes an individual a little bit stronger but as a society it makes us infinitely stronger and that strength protects the most vulnerable. Not vaccinating is a refusal to help those we are genetically luckier than. It's utter, mindless selfishness. And it really needs to be understood that way.

Gael23 · 03-09-2020 12:36PM

Say if I as a young healthy person get the vaccine and I come into contact with a person who had not been vaccinated, are we both protected?

Does the vaccine stop me hosting the virus and infecting others or just from entering my own body

iguana · 03-09-2020 12:42PM

Gael23 wrote: »

Say if I as a young healthy person get the vaccine and I come into contact with a person who had not been vaccinated, are we both protected?

Does the vaccine stop me hosting the virus and infecting others or just from entering my own body

We don't know yet but some reasonable suggestions are that, with a first vaccine at least, it might be the latter. A vaccinated person with a robust response to the vaccine will be protected from getting anything more than very mild symptoms but may still be a vector.

charlie14 · 03-09-2020 12:46PM

tobefrank321 wrote: »

That seems to be the plan in most countries, but again, can you force teachers and healthcare workers to take the vaccine? What are the penalties if some refuse? Even one or two non vaccinated pose a risk if they come into contact with someone infected elsewhere.

I cannot see a vaccine being mandatory in most countries.
Like any other vaccine the level of risk will depend on who, and how many, avail of it.
There have been figures floating around that if 60% acquiring naturally immunity, this would be sufficient to provide herd immunity to shield the most vulnerable, as they cannot acquire this natural immunity themselves.
If the uptake is the same or greater then it will have the same or greater effect.

The major advantage of a vaccine will be if it can be taken by the most vulnerable and those at greatest risk.
If it is, then I would imagine the uptake by that group would be of a very high percentage and the percentage uptake by the rest of the population would not be of that great an importance.

hmmm · 03-09-2020 12:54PM

charlie14 wrote: »

The major advantage of a vaccine will be if it can be taken by the most vulnerable and those at greatest risk.
If it is, then I would imagine the uptake by that group would be of a very high percentage and the percentage uptake by the rest of the population would not be of that great an importance.

Iguana's post above is a good explanation as to why that isn't the case. You need healthy people to take a vaccine to reduce the likelihood that someone who is infected will come in contact with someone who is vunerable. A vaccine doesn't provide perfect protection, and vaccines are often not effective for those who are "vulnerable".

If Granny takes the vaccine, her immune system might respond weakly. Your cousin who is on cancer treatment might not be able to take a vaccine. If you have the virus, they are still at risk.

charlie14 · 03-09-2020 01:12PM

hmmm wrote: »

Iguana's post above is a good explanation as to why that isn't the case. You need healthy people to take a vaccine to reduce the likelihood that someone who is infected will come in contact with someone who is vunerable. A vaccine doesn't provide perfect protection, and vaccines are often not effective for those who are "vulnerable".

If Granny takes the vaccine, her immune system might respond weakly. Your cousin who is on cancer treatment might not be able to take a vaccine. If you have the virus, they are still at risk.

I realise that the first vaccines to come on the market will not provide perfect protection for all.
But I would imagine that should they work for those outside of the most vulnerable, then they will give them a degree, relative to the uptake, of herd immunity. Especially if they prevent transmission, and would result in further research into developing a vaccine for at least some of those vulnerable categories.

Knex* · 03-09-2020 02:10PM

Might have been discussed before, but Novavax early stage results seem promising.

Think the headline is a bit misleading as it makes it sound like that its ready to be shipped to everyone, but good news nevertheless.

https://edition.cnn.com/2020/09/02/health/novavax-vaccine-safe/index.html

Hmmzis · 03-09-2020 02:14PM

A sub-unit vaccine candidate from Australia, pre-clinical results in mice and macaques:

https://www.biorxiv.org/content/10.1101/2020.09.01.278630v1.full.pdf+html

The paper explains quite a bit why the RBD sub-unit approaches don't seem to do so well in mice models and might not be the best for humans either. The macaques seem to respond really well to both of them, the RBD and full S proteins.

Cordell · 03-09-2020 02:22PM

Well, if anything this will result is some advancements in vaccine types and methods, the stuff that was supposed to happen a long time ago, with the first deadly outbreaks of this family of viruses.

Hmmzis · 03-09-2020 05:55PM

That would be some stroke of irony:

https://www.medrxiv.org/content/10.1101/2020.09.01.20182220v1.full.pdf+html

Trying to get a vaccine for SARS-cov-2 we might be collaterally taking out some of the common cold viruses as well. Most of the convalescent people would be now protected against at least some of the circulating hCoVs.

Hmmzis · 03-09-2020 09:36PM

On the treatment side, direct dosage of the vitamin D3 metabolite calcifediol:

https://www.sciencedirect.com/science/article/pii/S0960076020302764?via%3Dihub#tbl0005

There are some discrepancies between the treatment group and standard of care group, but to me they can't explain away the differences in outcomes (ICU 1:13, deaths 0:2). Needs a larger trial for sure I think.

hmmm · 03-09-2020 10:52PM

Hmmzis wrote: »

There are some discrepancies between the treatment group and standard of care group, but to me they can't explain away the differences in outcomes (ICU 1:13, deaths 0:2). Needs a larger trial for sure I think.

That's an incredible result, and Table 2 (Risk factors) is very interesting.

From a quick google, Calcifediol is not what you get in a Vitamin D supplement, that appears to be Cholecalciferol - is that correct?

Anyone know what the side effects are potentially from this?

hmmm · 03-09-2020 10:57PM

https://twitter.com/NPRKelly/status/1301602842625662976

Hmmzis · 03-09-2020 11:11PM

hmmm wrote: »

That's an incredible result, and Table 2 (Risk factors) is very interesting.

From a quick google, Calcifediol is not what you get in a Vitamin D supplement, that appears to be Cholecalciferol - is that correct?

Anyone know what the side effects are potentially from this?

Too much of it can be hard on the kidneys.
Calcifediol is what the liver makes from vitamin D3 (cholecalciferol), it's the actual active substance that we need D3 for.

Hmmzis · 04-09-2020 09:24AM

Another big (long read) update on the current vaccine candidates by Derek Lowe, last update from him was in July so there are a lot of new things in there and updates for the ones we know about already.

https://blogs.sciencemag.org/pipeline/archives/2020/09/03/coronavirus-vaccine-roundup-early-september

Grab a cuppa and have a read, it's very well put together. It's really good to see some intra-nasal and oral candidates appearing on the list, they would have (theoretically and with some pre-clinical data to back it up) the best chances of providing sterilizing immunity.

hmmm · 04-09-2020 12:29PM

Pfizer CEO expects to see data in late October:
https://www.fiercepharma.com/vaccines/pfizer-could-see-early-efficacy-data-for-coronavirus-vaccine-late-october-ceo

Also had this to say in the FT when asked whether they would come under pressure to release the vaccine early:
"Albert Bourla said the US drugmaker would never submit any vaccine for authorisation before it felt it was safe and effective.

“Pfizer last year had its 170th anniversary. It’s a long institution and I don’t plan to reduce its reputation in a year or two,” he said.
"

Hmmzis · 04-09-2020 02:41PM

Phase 1 results for "The Russian Vaccine" have now been published in The Lancet:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31866-3/fulltext

Looks fine at a first glimpse, quite similar to Oxford's ChAdOx1 (prime-boost putting it in the convalescent sera range and both CD4+ and CD8+ types present). The resulting titers against the vectors do look high though.

Stark · 04-09-2020 02:52PM

Hmmzis wrote: »

The resulting titers against the vectors do look high though.

For a layperson, why is that bad? Immune system overreacting, possible autoimmune side effects?

Hmmzis · 04-09-2020 04:41PM

Stark wrote: »

For a layperson, why is that bad? Immune system overreacting, possible autoimmune side effects?

Nope, it would make any potential boosters (or other vaccines) with same vector less potent. It's one of the often stated drawbacks of viral vectored vaccines, one doesn't just get a response against the expressed antigen, there will be a response to the vector itself as well. It makes you immune against the vaccine, to put it simpler (and the cold virus it's based on).

stephenjmcd · 04-09-2020 06:16PM

A bit of misleading headline.

But anyway the first line

"The World Health Organization has said it does not expect widespread immunisation against coronavirus until mid-2021"

Did anyone expect widespread vaccinations prior to mid 2021. I think most said mid 2021 was most likely for widespread vaccinations with priority groups getting it in early 2021 if possible depending on trials and approval.

https://twitter.com/rtenews/status/1301928366212296709?s=19

Gael23 · 04-09-2020 06:36PM

Nothing new there really

ShineOn7 · 04-09-2020 09:45PM

John Campbell has his fans and he has his detractors. But he's very optimistic

https://www.youtube.com/watch?v=d-oQI2RoXPI

Away With The Fairies · 05-09-2020 12:02AM

So the Oxford vaccine is based on an adenovirus. What do they put into it to make it work for this SARS-COV 2 virus?

Hmmzis · 05-09-2020 09:45AM

Away With The Fairies wrote: »

So the Oxford vaccine is based on an adenovirus. What do they put into it to make it work for this SARS-COV 2 virus?

The adenovirus is the vector (delivery mechanism). Inside the Ad shell is a modified genome (DNA in this case) that has the replication genes disabled and a big insertion added that produces the S protein of the SARS-cov-2 virus. Once the Ad virus has done its job of entering a cell the molecular gene transtription machinery will take this modified genome and build the proteins encoded in it, including the S protein that has been inserted there for the purpose of the vaccine effect.

There are ways how our cells then recognise the S protein as foreign (MHC is a big part of that) and then they start initiating an immune response.

There are some other vectors being tried out, including a modified flu virus and VSV (this one is already used in Ebola vaccines).

Away With The Fairies · 05-09-2020 09:53AM

Hmmzis wrote: »

The adenovirus is the vector (delivery mechanism). Inside the Ad shell is a modified genome (DNA in this case) that has the replication genes disabled and a big insertion added that produces the S protein of the SARS-cov-2 virus. Once the Ad virus has done its job of entering a cell the molecular gene transtription machinery will take this modified genome and build the proteins encoded in it, including the S protein that has been inserted there for the purpose of the vaccine effect.

There are ways how our cells then recognise the S protein as foreign (MHC is a big part of that) and then they start initiating an immune response.

There are some other vectors being tried out, including a modified flu virus and VSV (this one is already used in Ebola vaccines).

Thanks for this very knowledgeable post.

COVID-19: Vaccine/antidote and testing procedures Megathread [Mod Warning - Post #1]

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