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Life Sciences => Physiology & Medicine => COVID-19 => Topic started by: Petrochemicals on 09/04/2021 07:52:15

Title: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 09/04/2021 07:52:15
Given that the technology is tried and tested and  Chinese inactivated vaccine appears to work, should we have been persuing n inactivated virus vaccine in march 2020.

Would it have been quicker?
Would it have been faster?
Would it have been easier to produce?
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: CliffordK on 09/04/2021 08:40:25
I was ready for a vaccine to come out by late January a year ago. 

I think when the dust settles from this pandemic, the greatest tragedy will be all the delays in the vaccine rollout.

If one compares the COVID vaccine rollout to the 2009 Swine Flu rollout.  The Swine Flu was beginning to be reported in early April 2009.  COVID by the first of January 2020 (a full 3 months and change earlier).  Vaccines approved (USA) on September 15 (5 months later).  Late December 2009, vaccine available for all (USA), so about 8 months into the pandemic. 

With COVID, on the other hand, everything started 3 months earlier, and we were barely rolling out the first vaccine doses in late December, and now into April and still struggling to get people vaccinated.

We have nearly 3 million global deaths, 560 thousand dead in the USA, 127 thousand dead in the UK, 167 thousand in India, and still counting.

Had we gotten the vaccine out by the end of October, the numbers might have been 1 million dead, kids would be back in school, and life would be returning to normal.

Somehow we have the capacity to get flu shots out to half the population every year (which I got one last fall), but struggle with capacity issues for the COVID vaccine. 

Somehow we accept a 50% efficacy for the flu shots (it's just the flu that kills thousands of vulnerable people), but needed better for COVID.

Yet, a 50% efficacy of the shots may still have kept millions of people out of the hospital, and out of the morgue.

And we could have followed up with a 2nd or 3rd vaccine after an early one.

Obviously the FDA and other similar organizations in other countries are vital for regulating drugs, and safety of chemical drugs.  But, I wonder if vaccine safety is different.  Yes, there are dosing issues...  but...  that could be determined quickly. 

Then there is real world efficacy.  And, of course the risk of giving people a false sense of security.  But, even a moderate efficacy might have reduced millions of infections, and potentially kept those that got the disease from being admitted to hospitals.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Bored chemist on 09/04/2021 08:45:48
This viral infection has an R value of about 3.
A vaccine that reduces it by 50% will take it to about 1.5
That's still more than one.
So that vaccine will not stop an outbreak.
So, the answer to the question is: no we should not have wasted time on something which wouldn't have done the job.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: chris on 09/04/2021 09:01:46
Valneva, one of the vaccine manufacturers, is going down the route of inactivated virus.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: CliffordK on 09/04/2021 11:02:19
This viral infection has an R value of about 3.
A vaccine that reduces it by 50% will take it to about 1.5
That's still more than one.
So that vaccine will not stop an outbreak.
So, the answer to the question is: no we should not have wasted time on something which wouldn't have done the job.
People may like to have a base replication number but I'm not sure one can consider the R-Value as constant.

Here in the USA we've been on a quite a roller coaster ride, and are now entering our fourth wave.

So, between April and May, cases were decreasing. (R < 1),
Late July to early September, cases were also decreasing (R < 1)
And January 9 through mid March cases were also decreasing (R < 1)

Masks, social distancing, etc, can all reduce spread.  It is quite possible the warm summer + a vaccine would have reduced our summer wave, and put us in a better position for the coming fall.

COVID is under reported, but consensus puts the general population infection fatality rate around 0.3% to 1%. 

Early studies were showing a very low fatality rate in vaccinated patients with the current vaccines.  Perhaps that will be better defined now that we have millions vaccinated.  It is quite possible that even a marginal vaccine would reduce both transmission and the fatality rate. 

The biggest risk would be giving individuals a false sense of security, but getting kids back to school and returning to "normal" earlier could have been very beneficial.

The efficacy studies of the current vaccines only studied developing the disease (or developing symptomatic disease).  If transmission was also reduced, that could further reduce the R value.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: evan_au on 09/04/2021 11:48:17
Quote from: CliffordK
Somehow we have the capacity to get flu shots out to half the population every year (which I got one last fall), but struggle with capacity issues for the COVID vaccine.
There is a fundamental difference here:
Flu Vaccine: There is a well-oiled international machine for detecting and prioritizing new flu variants, for manufacturing a vaccine (in massive warehouses filled with chicken eggs), and distributing it to those who need it.
- A new set of priority variants is identified every 6 months, and bulk manufacturing is available before those variants start to spread in the winter of the target hemisphere.
- The factory is unchanged, the manufacturing process is unchanged
- the vaccine safety is well-tested over many years, accelerating the safety trials
- this makes approval very straightforward.

COVID-19 Vaccine: The international network for detecting and identifying new respiratory diseases apparently ignored it, because it wasn't a flu virus.
- In fact, it was a coronavirus, for which there had never been a successfully deployed vaccine in humans
- They had to work out how to create a new coronavirus vaccine, and then mass-produce it
- This has resulted in a number of vaccine approaches, all of which have some degree of novelty
- This requires a new factory and production techniques
- The safety of these novel vaccines needs to be tested carefully in clinical trials
- Genetic engineering techniques were used extensively in design of these new vaccines. Again, this is a newish technique.
- The main reason that it could be done so quickly is that there was a competition several years ago to develop vaccine "platforms" that could be quickly adapted to a new pandemic. These platforms delivered some of the first approved COVID-19 vaccines.

Yes, availability of the COVID-19 vaccines was slower than the annual seasonal flu vaccine (which is available before the start of the flu season).
- I think that the causes are entirely reasonable
- Frankly, I think that it is amazing that the COVID-19 vaccines are available as quickly as they were
- I agree there are lots of production problems; you expect this with ramp-up of a new product and process
- The main risk is that the large number of COVID-19 cases in the worldwide community will continue to spawn large numbers of new variants, some of which are likely to escape the current vaccines.

I think we can aspire to having a COVID-19 vaccine process that is as effective at dealing with variants as the flu virus is today
- And hopefully, an international monitoring network that will detect new pandemic candidates, even if it doesn't match the expectations created by the last pandemic.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: evan_au on 09/04/2021 11:50:14
Quote from: OP
Chinese inactivated vaccine appears to work
Please point to the peer-reviewed paper showing the efficacy, and how they calculated it.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 09/04/2021 14:39:29
Quote from: OP
Chinese inactivated vaccine appears to work
Please point to the peer-reviewed paper showing the efficacy, and how they calculated it.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext

There is a sort of greyness to the current situaltion as there is with astrazenica.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Bored chemist on 09/04/2021 15:35:40
but I'm not sure one can consider the R-Value as constant.
True, and I spent quite a lot of time failing to explain that to people here who would not listen.

However, the point remains that only dropping the infection rate by half isn't really good enough- it just means that people die over a longer period (with a slight additional reduction if that stops healthcare getting overwhelmed).


There is a sort of greyness to the current situaltion as there is with astrazenica.
The situation with AZ is that people are worried about a blood clot risk from a vaccine which might allow them to take a foreign holiday in which which the air travel  exposes them to roughly a hundred fold greater risk of a clot than the vaccine.

That's not "grey" that's scaremongering.


Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: set fair on 09/04/2021 19:13:40
The only thing to seriously complain about is the manufacturing capacity. A goal of at least 50 million doses a day should have been set. It's a bit rich for Tedros to lament slow rollout in poorer countries - he is the one who should have set the goal. Of course wealthy countries will vaccinate their own first.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Bored chemist on 09/04/2021 20:31:51
Given that the technology is tried and tested and  Chinese inactivated vaccine appears to work, should we have been persuing n inactivated virus vaccine in march 2020.

Would it have been quicker?
Would it have been faster?
Would it have been easier to produce?

There's an implication there that the various drug companies round the world might have got their managerial boards together and decided "I know; let's not try to be first to market with an effective vaccine, and let's make it unduly difficult".

There's also an implication that
"Would it have been quicker?"
is different from
"Would it have been faster?"

But that's just a comment on the OP's wisdom
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: evan_au on 09/04/2021 21:40:34
Quote from: Petrochemicals
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext
That is a Phase 1 trial (144 participants), which is about Safety: Will it harm a large number of the participants?
- & Phase 2 trial (600 participants), which is aimed at Dosing to produce effective antibodies (and look closer at side-effects)
- These phases are important, to minimize harm, and ensure it has some chance of working

To get an idea of efficacy, you need a Phase 3 trial, typically with 30,000 participants.
- You need to compare the number of people who catch the disease, and the number who die with/without the vaccine
- This paper does not do this.
- That is why the last line says
Quote from: Sinovac trial
In summary, CoronaVac was well tolerated and induced humoral responses against SARS-CoV-2, supporting the approval of emergency use of CoronaVac in China and in three phase 3 studies. The protective efficacy of CoronaVac remains to be determined.

So the rollout in China started without actually knowing the efficacy....
- There is a risk that National Pride will determine the deployment of home-grown vaccines, rather than the Clinical Efficacy
- But other countries should expect to see the Clinical Efficacy before they decide to deploy a vaccine

So the question remains:
Quote from: evan_au
Please point to the peer-reviewed paper showing the efficacy, and how they calculated it.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 10/04/2021 04:41:57
Quote from: Petrochemicals
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext
That is a Phase 1 trial (144 participants), which is about Safety: Will it harm a large number of the participants?
- & Phase 2 trial (600 participants), which is aimed at Dosing to produce effective antibodies (and look closer at side-effects)
- These phases are important, to minimize harm, and ensure it has some chance of working

To get an idea of efficacy, you need a Phase 3 trial, typically with 30,000 participants.
- You need to compare the number of people who catch the disease, and the number who die with/without the vaccine
- This paper does not do this.
- That is why the last line says
Quote from: Sinovac trial
In summary, CoronaVac was well tolerated and induced humoral responses against SARS-CoV-2, supporting the approval of emergency use of CoronaVac in China and in three phase 3 studies. The protective efficacy of CoronaVac remains to be determined.

So the rollout in China started without actually knowing the efficacy....
- There is a risk that National Pride will determine the deployment of home-grown vaccines, rather than the Clinical Efficacy
- But other countries should expect to see the Clinical Efficacy before they decide to deploy a vaccine

So the question remains:
Quote from: evan_au
Please point to the peer-reviewed paper showing the efficacy, and how they calculated it.
Ok I'll try to find a phase 3 paper
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 10/04/2021 04:49:47
Valneva, one of the vaccine manufacturers, is going down the route of inactivated virus.
Does this mean it is not particularly fast to achieve?
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: alancalverd on 10/04/2021 09:40:09
Presumably.

Never  mind the humanitarian aspect: given an immediate world market for some 7 billion doses of whatever works, nobody with the capacity to develop and manufacture a vaccine is going to waste time doing anything else.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: set fair on 14/04/2021 09:39:43
Sinovac's coronavac looks like it's about on par with other vaccines. Perhaps not quite as good but given a bad press
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 14/04/2021 13:31:07
Sinovac's coronavac looks like it's about on par with other vaccines. Perhaps not quite as good but given a bad press
That is the grey area. Astra zenica is 60 percent efficient at stoppi g infection, but according to the USA was 100 percent effective in stopping mortality. It has also been suggested AZ is 90 percent efficient at stopping hospitalisation in a Scottish study. The sinovac seems to be similarly ambiguous.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: set fair on 14/04/2021 16:38:43
Time to approval is similar also.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 15/04/2021 13:05:25
Time to approval is similar also.
Time to approval may be similar as desisions are desisions, but time to develop and time to trial may be far smaller, it is after all a very well trodden path. China did produce it very quickly. The flu vaccine is an inactivated virus that is rolled out very quickly, the only problem with the flu vaccine is production as it is cultured in chicken eggs. I wonder how sinovac is produced.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Bored chemist on 15/04/2021 22:34:17
the only problem with the flu vaccine is
... that it is irrelevant.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 16/04/2021 23:49:38
Sinovac in action.

https://www.bbc.co.uk/news/world-latin-america-56731801

Does this mean it is ineffective entirely or just against the Brazil strain. Would producing a deactivated virus to the Brazilian strain be faster or can a Genetic engineered vaccine cover much more all in one.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: evan_au on 17/04/2021 01:48:32
Quote from: Petrochemicals
Would producing a deactivated virus to the Brazilian strain be faster or can a Genetic engineered vaccine cover much more all in one.
It looks like the sinovac method of inactivating the COVID virus is a generic technique that binds up the viral RNA so it can't replicate in a human cell.
- This method should be just as effective at inactivating all strains of COVID-19 (including Brazilian, South African and Kent varieties)

What they need to do is to start bulk-manufacturing multiple strains of COVID virus, inactivating them, and producing a "polyvalent" vaccine that works against multiple strains.

This sounds easier than genetic engineering the Wuhan virus to look like all these other strains, and then bulk-manufacturing that hybrid...

It will require an extensive clinical trial (in multiple countries) to test the polyvalent vaccine against multiple different strains...
- All of the vaccine manufacturers are now calculating the odds on what will be the dominant COVID variant(s) in 6 months time, so they can start developing polyvalent vaccines/boosters.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: set fair on 17/04/2021 02:02:41
What they need to do is to start bulk-manufacturing multiple strains of COVID virus, inactivating them, and producing a "polyvalent" vaccine that works against multiple strains.

Too right. The E484K mutation was predicted (from lab experiments last august)) to bloom once people's anyibody & Tcell levels fell enough for people to get reinfected. So they could have started testing it then and had it in the vaccines a few months ago.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Jolly2 on 10/05/2021 23:12:49
Given that the technology is tried and tested and  Chinese inactivated vaccine appears to work, should we have been persuing n inactivated virus vaccine in march 2020.

I would have gone with an inactivated virus vaccine over an mRNA, simply because it should elicit a wider range of immune response, and potentially help those vaccinated against mutations as a result. Still people that have had covid maybe shouldnt get the vaccine as they now have immunity, should maybe start a thread to discuss the implications of vaccinating someone with aquired immunity as the vaccine will trigger the activation of the reserve antibodies from the original infection,  and potentially interfere.

Would it have been quicker?
Would it have been faster?

Arnt they the same question? The mRNA and Chinese vaccines all started trials at more or less the same time, its apparently cheaper to produce mRNA vaccine but atleast for the current vaccines doent appear to be any quicker.

Would it have been easier to produce?

Cheaper for the mRNA not sure it's easier. Rather simple process to produce a virus and then deactivate it maybe more time consuming as you have to wait for the virus' to develop. Not sure it's as easier to produce an mRNA strand and wrap it in a nanoparticle plus the mRNA is still a novel treatment.

Found this link from politics everything you need know about the Chinese Inactivated virus vaccine. https://www.politico.eu/article/everything-you-need-to-know-china-coronavirus-vaccines/
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Jolly2 on 10/05/2021 23:16:50
Quote from: Petrochemicals
Would producing a deactivated virus to the Brazilian strain be faster or can a Genetic engineered vaccine cover much more all in one.
It looks like the sinovac method of inactivating the COVID virus is a generic technique that binds up the viral RNA so it can't replicate in a human cell.
- This method should be just as effective at inactivating all strains of COVID-19 (including Brazilian, South African and Kent varieties)

What they need to do is to start bulk-manufacturing multiple strains of COVID virus, inactivating them, and producing a "polyvalent" vaccine that works against multiple strains.

This sounds easier than genetic engineering the Wuhan virus to look like all these other strains, and then bulk-manufacturing that hybrid...

It will require an extensive clinical trial (in multiple countries) to test the polyvalent vaccine against multiple different strains...
- All of the vaccine manufacturers are now calculating the odds on what will be the dominant COVID variant(s) in 6 months time, so they can start developing polyvalent vaccines/boosters.

Are you suggesting they will give a polyvariant inactived virus vaccine as a booster to people vaccinated with the mRNA shots?

Wont the antibodies gernerated from the original vaccine be called in to fight it, and therefore interfere with the actual effectiveness?

If I was in a country that hasnt yet started a vaccination program,  I would be looking for a polyvariant inactived virus vaccine for all those not having natural immunity. to be the first vaccine program deployed. But in countries where mRNA vaccines have already been used I'm not sure it would be as effective, simply because the now present antibodies might interfere.

We need effective treatments.
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Bored chemist on 11/05/2021 18:59:02
We need effective treatments.
We have several.
And the "first to market" were not inactivated virus ones.

So, if the industry had decided to do what you advocate, the vaccination program would have taken longer to get started, and more people would have died.

Don't you think it's time to stop saying it was a good idea?

And, of course, as that article says.
"But the Chinese jabs are no magic bullet. The efficacy data supporting the vaccines is neither public nor peer-reviewed, and many worry that some of them might not be as effective as their Western counterparts. EU countries that have or will use the vaccines are doing so without the European Medicines Agencys sign-off meaning they must assume liability if an issue arises later."
Title: Re: Should we have tried the inactivated virus approach to vaccines for Covid-19?
Post by: Petrochemicals on 03/06/2021 13:17:44
Would it have been quicker?
Would it have been faster?

Arnt they the same question? The mRNA and Chinese vaccines all started trials at more or less the same time, its apparently cheaper to produce mRNA vaccine but atleast for the current vaccines doent appear to be any quicker.
Yes they are jolly and thanks for the info. Do they grow this one in chicken eggs too?

It seems Chile may be experiencing the effect of the inactivated virus being the wrong strain, as is seen in flu vaccines. Even though they are heavily vaccinated in Chile it does not seem to have made a dent in either the cases or mortality figures. As Jolly points out, it is harder to make the deactivated virus vaccine so it must be harder to change strain types too.