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Now tracking the new emerging South Africa Omicron Variant

Is it time to move on from mRNA vaccines

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Hazelpad View Drop Down
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    Posted: December 10 2021 at 3:59am

This is just my own opinion and idea so no references at bottom of post. Feel free to debate all opinions welcome.

My overriding concern is what appears to be a monopoly on vaccine designed.  Trying to stop a pandemic with a vaccine designed around one single protein of the virus doesnt make sense to me.  Not everyone will process epitopes from the spike protein efficiently. They need other parts of the virus to make the full effective response.  It's the way we evolved, and it's maybe why China took a different approach and designed their major covid vaccine around the whole virus.( they predominantly use the more traditional whole vaccine attenuated design over mRNA designed).  

Immunologly we are all genetically different so when 2 people are infected with the same virus the whole virus is pulled to pieces and bits of that virus are held out to our immune system.  Like waving a scented rag to a sniffer dog.  Thing is genetically different people wave different scents to their immune sniffing dog, the scent your dog (immune system) responds to will be different from the person next to you.  If you wave the wrong scent you get a muted response from your dog, it may go after it once but isnt stimulated so soon stops attacking the scent, or sometimes no response. So many people out there may not make good responses to the spike protein.  They need another part of the virus.  Maybe one of its assembly protein or one in its outer capsule. 

It's called immunodominant epitopes and maybe the spike protein does not contain certain peoples immunodominant sequence.

The Chinese use whole viral vaccines.  That is they take the virus and treat it so it cant replicate.  Then stick this virus in the vaccine.  That way the immune system gets access to the whole range of viral proteins not just the single spike protein.  They give the immune system a choice from a buffet we give it a set single course of one protein. I am not saying it's a perfect vaccine but it's different to ours. Worth looking at this traditional method as it's the way we always did it before mRNA.

I appreciate why we went down this line, but I cant understand why we have just stopped with our vaccine design and gone with completely with mRNA vaccine.  

I dont know if omicron is due to selective pressure from vaccine or due to reassortment with another coronavirus in the same individual (pick up genetic material from common cold virus) some sequencing data may indicate this.   However we cant be dominated by a few vaccine manufacturers.  There are other approaches we need to explore.

My fear is we are just creating a market for the mRNA vaccines and that this is too narrow a focus.

Open up vaccine and treatment research but it seems to have stagnated in Europe and USA.and we have gone  mRNA vaccine design or bust. 

I am not saying mRNA vaccines did not have and still has a part to play and have no doubt they saved and are still saving lives,but is it time to move on from relying on this strategy but we seemed to have squashed all other vaccine competitors or candidates.

Hz x



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Thank you Hazelpad, I couldn't agree with you more. My vaccine hesitancy is entirely due to the technology of the vaccine. If Sinovac, the Chinese attenuated traditional vaccine, was available in New Zealand, I would happily consider having it. That style of vaccine technology has been around for years and has proven to be safe and effective. My family is fully vaccinated on everything except Covid. I will not have an mRNA vaccine or even the nanotechnology Novavax one until there is ample long term safety data on it, but I would have Sinovac. 

I'm also concerned that mRNA vaccines will replace the traditional type. They are already talking about replacing the flu jab with mRNA ones. I guess there's more money to made from them. I can't think for one moment that they are being suggested because they are better for us. But call me a sceptic.....

"Once you've decided that something's absolutely true, you've closed your mind on it, and a closed mind doesn't go anywhere. Question everything. That's what education's all about." ~ David Eddings
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I am a bit confused  at the apparent concern that only mRNA vaccines are being used , more people in the world have been and will continue to be vaccinated with none mRNA vaccines than with mRNA vaccines ( AstraZeneca+sinovax+Sputnik ).

The mRNA vaccines appear to have a higher efficacy than the none mRNA vaccines.

If someone is concerned about having part of a viruses sequence either injected into them (or created inside them), then why would they be less concerned with having the entire virus sequence  injected inside them????

The longer the sequence of the novel virus (in this case covid 19) that is inside a person then surely the greater the chance that more people would have adverse reactions to parts of that sequence.

 In the UK currently 73 people (AstraZeneca vaccinated) are assumed to have died due to clots caused by their bodies reaction to part of the virus sequence (note if they had caught covid it is estimated that they would have been 8 times more likely to have had fatal blood clots due to their bodies reaction to the same sequence, and being realistic the chances of any of us in the UK being able to avoid covid long term is practically  zero!!!!,)

KiwiMum , you appear to have some strange ideas about how vaccines work , NO vaccine is 100% safe or effective, NO vaccine can stop you catching something , vaccines work by priming the bodies defenses so that you have a better chance of defeating the attack.




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Post Options Post Options   Thanks (0) Thanks(0)   Quote A-I Quote  Post ReplyReply Direct Link To This Post Posted: December 10 2021 at 9:49pm

Originally posted by Shady Shady wrote:

I am a bit confused  at the apparent concern that only mRNA vaccines are being used , more people in the world have been and will continue to be vaccinated with none mRNA vaccines than with mRNA vaccines ( AstraZeneca+sinovax+Sputnik ).

The mRNA vaccines appear to have a higher efficacy than the none mRNA vaccines.

If someone is concerned about having part of a viruses sequence either injected into them (or created inside them), then why would they be less concerned with having the entire virus sequence  injected inside them????

The longer the sequence of the novel virus (in this case covid 19) that is inside a person then surely the greater the chance that more people would have adverse reactions to parts of that sequence.

 In the UK currently 73 people (AstraZeneca vaccinated) are assumed to have died due to clots caused by their bodies reaction to part of the virus sequence (note if they had caught covid it is estimated that they would have been 8 times more likely to have had fatal blood clots due to their bodies reaction to the same sequence, and being realistic the chances of any of us in the UK being able to avoid covid long term is practically  zero!!!!,)

KiwiMum , you appear to have some strange ideas about how vaccines work , NO vaccine is 100% safe or effective, NO vaccine can stop you catching something , vaccines work by priming the bodies defenses so that you have a better chance of defeating the attack.




Meh you were saying??? Ima throw a small pox vaccine in the pot as well. LOL

https://www.cdc.gov/vaccines/parents/diseases/index.html

"Facts don't care about your feelings" I'M A UNVAXXED DEVIL so kiss my rebel ass.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote carbon20 Quote  Post ReplyReply Direct Link To This Post Posted: December 10 2021 at 10:25pm

AI, you mentioned Smallpox vaccine in another post,

You do know that smallpox is DNA based ,

The flu and Covid viruses are RNA ,as you will know DNA is far more stable than RNA, therefore it's easier to produce a vaccine as it  mutants very little at all stays very much the same ,

Flu ,and Covid viruses change all the time ,that's why we have never cured the Common cold,we will never conquer covid,

vaccines just stop you getting really sick and and keep you out of hospital.nit sure about the mutations rates of the other disease,at the moment will now go and look.....

Take care all 😷😉💉

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Everything we hear is an opinion, not a fact. Everything we see is a perspective, not the truth.🖖

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Just pulled this off the net..

Thanks I'm learning new stuff myself......


Some viruses mutate frequently, such as those that cause the common cold (e.g., rhinovirus), influenza, hepatitis C and HIV. Others like the chicken pox virus (varicella-zoster virus) and the mono virus (Epstein-Barr virus), mutate less frequently. Viruses like SARS-CoV-2 are RNA viruses and they mutate frequently.7 Sept 2021

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Sorry Hazelpad,

 getting off topic 

I think mRNA will be the main way of making vaccines in the future,

Thats doesn't mean abandoning other methods,but given a bird flu pandemic, normal vaccine production wouldn't work that well,as the virus kills the eggs that the vaccine is Produced,as far as I aware.......

Take care all 😷😉💉





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Post Options Post Options   Thanks (0) Thanks(0)   Quote A-I Quote  Post ReplyReply Direct Link To This Post Posted: December 10 2021 at 11:27pm

Originally posted by carbon20 carbon20 wrote:

AI, you mentioned Smallpox vaccine in another post,

You do know that smallpox is DNA based ,

The flu and Covid viruses are RNA ,as you will know DNA is far more stable than RNA, therefore it's easier to produce a vaccine as it  mutants very little at all stays very much the same ,

Flu ,and Covid viruses change all the time ,that's why we have never cured the Common cold,we will never conquer covid,

vaccines just stop you getting really sick and and keep you out of hospital.nit sure about the mutations rates of the other disease,at the moment will now go and look.....

Take care all 😷😉💉

The reason they haven't cured the common cold is that it is actually a group of about 200 viruses which include Rhino viruses, Corona viruses, RSV and Para influenza. And about 20% to 30% of those 200 common cold viruses are unknown and unidentified. That's why the common cold hasn't been cured. And yes they are all mutating all the time, that's what viruses do.

"Facts don't care about your feelings" I'M A UNVAXXED DEVIL so kiss my rebel ass.
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But do you agree they mutate at different rates,some barely changing, and that's why vaccines work with some diseases,and not others aka Covid.....

Take care all 😷😉💉

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Post Options Post Options   Thanks (1) Thanks(1)   Quote Hazelpad Quote  Post ReplyReply Direct Link To This Post Posted: December 11 2021 at 6:52am

Hi Shady

Thanks for your reply and you bring up a good point that

  1. If some people are concerned about getting a part of a virus sequence injected into them why on earth would they want the whole sequence instead.

 

  1. The longer the sequence the greater chance the adverse reaction.

 

1:  Firstly my concern isn’t about  getting an RNA sequence  injected, I think you are missing the point of my post.  My concern is it is too narrow and specialised a target.   A complete immune response to a virus (even in vaccine induced immunity)  requires a balanced interplay between neutralising antibodies,   specific CD4+ and CD8+ T cells and  with innate immune systems.   The more tuned this is, the more effective the vaccine is.  By effective I mean not just in preventing illness long term, but also in preventing onward spread.  To get all these components of the immune system  in sync , ( right location, optimum amount etc )  is required for effective immunity.    I just don’t see this possible  by  using only  the spike protein as a sole antigen as these vaccine do .  Yes they produce neutralising antibodies against one small bit of the virus,  but we need more than that for longer immunity.   These vaccines only give you immunity to a single spike protein they do  not give you  immunity to the virus like the more traditional vaccines do.  If the spike protein changes your immunity is lost, but those that get attenuated vaccines will have antibodies  to other parts of the virus, and have other immune actions to offset this.  They have other guns in their immune system, a single target mRNA shot only hands you one weapon that the enemy can easily generate a shield against.

 

Sars-CoV2 virus is more complicated than just the spike protein.   There are at least  4 other major proteins but mRNA and Az don’t target any of these others at all.   Does this matter, well probably it does,  For example  during  infection the immune response to Sars-CoV2  produces high levels of antibodies against the viruses N-protein.  This is the most abundant protein in the  virus.  The antibodies to N aren’t neutralising, they are of a different class called IgG2a antibodies.   These IgG2a bind virus and  form a bridge by also binding to cells called macrophages.  This pulls the virus in tethering it to macrophages which then eat and destroy it.  Macrophages also warn other cells and produce the correct cytokines to programme the immune system.  N protein antibodies are also thought to work inside an infected cell which was unheard of.    mRNA vaccines don’t have this N protein, don’t produce IgG2a against N.  Have nothing to do with it.

 

 We also don’t think  mRNA spike protein can produce a type of antibody called IgA specific  antibodies which are the main  defence at the mucosal surface,  so they are unlikely to stop you getting infected in the upper airways so vaccinated people probably can acquire the virus, carry it around in their nose and pass it on but don’t themselves get too sick.   This is a nightmare scenario, producing lots of asymptomatic infection, an ideal breeding ground for the virus.

 

A vaccine should also be able to activate an adaptive cellular IR and not just neutralising antibodies.  By this we mean CD8+ memory CD4+ memory, it should be able to keep it within a tolerable range.  mRNA vaccine trials to Zika and Rabies etc gave wide disparity in  magnitude and longlivity of their immune responses much as we are seeing today. Again this may signal one size of antigen doe not fit all and there are no back u antigens in these mRNA vaccines.

 

I don’t disapprove of the vaccines and in no way am I saying the mRNA vaccines (or the plasmid DNA vaccines like Astra Zeneca which also only includes the spike protein receptor binding domain from the wild type virus) don’t have a role to play.  I do however question if this antigen target is too specialised and narrow to elicit any long standing immunity and especially prevent onward infection.  

I feel we should be looking more at mucosal versions using attenuated versions of the virus, ( mucosal vaccination has huge potential for respiratory viruses)  mRNA vaccines cant go down this route as the adjuvant lipid  they are   enclosed in are far  too powerful and immunogenic  for the mucosal route.

 

2: Lastly concerning your point about  “longer the sequence the greater chance the adverse reaction.”  I do disagree with you.  There is no correlation of that.  It is not the quantity of the material it is the quality.  Vaccines induced immunity is not the same as natural immunity so vaccines often require an “infection signal” called an adjuvant to pull in the immune cells to make a response.  The adjuvant is responsible for most of your side effects not the viral material.  mRNA and DNA are not immunogenic in most people.  Live attenuated don’t use adjuvants.

 

While I have concerns   about long term effectiveness of both the mRNA vaccines and the recombinant viral vectors designed so to only include the  code spike protein   ( Az, Johnson and Johnson and sputnik V).  I apologise if your part of the world are using different vaccines.   Here in the UK we only have access to the spike protein expressing viral vectors,  and no access to protein or live attenuated  in the near future.

Of course we will all have our own opinions and that’s what makes science.   

Hz

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh Quote  Post ReplyReply Direct Link To This Post Posted: December 11 2021 at 7:24am

[url]https://twitter.com/ginnymooy[/url] or https://twitter.com/ginnymooy retweet; Omicron: New report from UK Vlag van het Verenigd Koninkrijk Health Security Agency (link below) not good. It confirms high transmissibility more than delta as in ZA. Also early vaccine effectiveness data after 3 doses only 70-75% vs symptomatic illness https://assets.publishing.service.gov.uk/government/upl

oads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf4/4 Omicron 2: on top of that virus neutralizing antibody data from Germany shows rapid decline within a few months Post 3rd dose. The decline for me is an unhappy surprise, I thought it would hold up better after 3 doses. We need guidance on potential 4th dose, which vaccine?

DJ [url]https://twitter.com/PeterHotez[/url] or https://twitter.com/PeterHotez

Our low cost 

 

  recombinant protein COVID-19 vaccine is being scaled/produced in India 

 and Indonesia 

. Our aspirational goal is to vaccinate the world's low-income countries in the coming months

Maybe new vaccines offer hope ? 

Hazelpad, I get the impression mRNA vaccines may not "do the GLOBAL job"....We need vaccines that also are better atstopping spread-dealing with the virus getting into cells in the "most wide way" possible (opposite what present vaccines may do now-to "narrow" ?)

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Post Options Post Options   Thanks (0) Thanks(0)   Quote KiwiMum Quote  Post ReplyReply Direct Link To This Post Posted: December 11 2021 at 12:01pm

Originally posted by Hazelpad Hazelpad wrote:

Hi Shady

Thanks for your reply and you bring up a good point that

  1. If some people are concerned about getting a part of a virus sequence injected into them why on earth would they want the whole sequence instead.

 

  1. The longer the sequence the greater chance the adverse reaction.

 

1:  Firstly my concern isn’t about  getting an RNA sequence  injected, I think you are missing the point of my post.  My concern is it is too narrow and specialised a target.   A complete immune response to a virus (even in vaccine induced immunity)  requires a balanced interplay between neutralising antibodies,   specific CD4+ and CD8+ T cells and  with innate immune systems.   The more tuned this is, the more effective the vaccine is.  By effective I mean not just in preventing illness long term, but also in preventing onward spread.  To get all these components of the immune system  in sync , ( right location, optimum amount etc )  is required for effective immunity.    I just don’t see this possible  by  using only  the spike protein as a sole antigen as these vaccine do .  Yes they produce neutralising antibodies against one small bit of the virus,  but we need more than that for longer immunity.   These vaccines only give you immunity to a single spike protein they do  not give you  immunity to the virus like the more traditional vaccines do.  If the spike protein changes your immunity is lost, but those that get attenuated vaccines will have antibodies  to other parts of the virus, and have other immune actions to offset this.  They have other guns in their immune system, a single target mRNA shot only hands you one weapon that the enemy can easily generate a shield against.

 

Sars-CoV2 virus is more complicated than just the spike protein.   There are at least  4 other major proteins but mRNA and Az don’t target any of these others at all.   Does this matter, well probably it does,  For example  during  infection the immune response to Sars-CoV2  produces high levels of antibodies against the viruses N-protein.  This is the most abundant protein in the  virus.  The antibodies to N aren’t neutralising, they are of a different class called IgG2a antibodies.   These IgG2a bind virus and  form a bridge by also binding to cells called macrophages.  This pulls the virus in tethering it to macrophages which then eat and destroy it.  Macrophages also warn other cells and produce the correct cytokines to programme the immune system.  N protein antibodies are also thought to work inside an infected cell which was unheard of.    mRNA vaccines don’t have this N protein, don’t produce IgG2a against N.  Have nothing to do with it.

 

 We also don’t think  mRNA spike protein can produce a type of antibody called IgA specific  antibodies which are the main  defence at the mucosal surface,  so they are unlikely to stop you getting infected in the upper airways so vaccinated people probably can acquire the virus, carry it around in their nose and pass it on but don’t themselves get too sick.   This is a nightmare scenario, producing lots of asymptomatic infection, an ideal breeding ground for the virus.

 

A vaccine should also be able to activate an adaptive cellular IR and not just neutralising antibodies.  By this we mean CD8+ memory CD4+ memory, it should be able to keep it within a tolerable range.  mRNA vaccine trials to Zika and Rabies etc gave wide disparity in  magnitude and longlivity of their immune responses much as we are seeing today. Again this may signal one size of antigen doe not fit all and there are no back u antigens in these mRNA vaccines.

 

I don’t disapprove of the vaccines and in no way am I saying the mRNA vaccines (or the plasmid DNA vaccines like Astra Zeneca which also only includes the spike protein receptor binding domain from the wild type virus) don’t have a role to play.  I do however question if this antigen target is too specialised and narrow to elicit any long standing immunity and especially prevent onward infection.  

I feel we should be looking more at mucosal versions using attenuated versions of the virus, ( mucosal vaccination has huge potential for respiratory viruses)  mRNA vaccines cant go down this route as the adjuvant lipid  they are   enclosed in are far  too powerful and immunogenic  for the mucosal route.

 

2: Lastly concerning your point about  “longer the sequence the greater chance the adverse reaction.”  I do disagree with you.  There is no correlation of that.  It is not the quantity of the material it is the quality.  Vaccines induced immunity is not the same as natural immunity so vaccines often require an “infection signal” called an adjuvant to pull in the immune cells to make a response.  The adjuvant is responsible for most of your side effects not the viral material.  mRNA and DNA are not immunogenic in most people.  Live attenuated don’t use adjuvants.

 

While I have concerns   about long term effectiveness of both the mRNA vaccines and the recombinant viral vectors designed so to only include the  code spike protein   ( Az, Johnson and Johnson and sputnik V).  I apologise if your part of the world are using different vaccines.   Here in the UK we only have access to the spike protein expressing viral vectors,  and no access to protein or live attenuated  in the near future.

Of course we will all have our own opinions and that’s what makes science.   

Hz

Wow. Great info and explanation Hazelpad. Thanks.

"Once you've decided that something's absolutely true, you've closed your mind on it, and a closed mind doesn't go anywhere. Question everything. That's what education's all about." ~ David Eddings
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Shady Quote  Post ReplyReply Direct Link To This Post Posted: December 11 2021 at 4:37pm

@Hazlepad - I will start by saying I am sure that I agree with you more than I disagree with you.

I do understand your point about the majority of the vaccines being targeted at the spike protein , perhaps the title of the thread is not perfect as it implies you are more concerned with the delivery mechanism rather than the target ?

If I was in charge of the world then personally I would want a range of different approaches as putting all or most of your eggs in one basket is risky , it is a shame that it is the Chinese vaccine that has taken the more traditional route as like most people I have a degree of scepticism surrounding any covid data that comes out of China.

Having said that , the logic of going for the spike protein makes sense and so far the data * seems to show that the vaccines targeting the spike protein are more effective than either the Chinese vaccine or by having immunity by infection, how long that will remain the case is open to question.

My point about the amount of sequence that is used was more aimed at the anti-vaxers , as I can already imagine the objections they would raise as already the best info at present suggests that at least some of the fatal reactions to the AstraZeneca vaccine have been due to the bodies reaction to part of the covid sequence rather than part of the vector virus sequence.It is almost certainly the same with Pfizer and/or the same problem would arise using the whole covid sequence. What is not known is how many/any of the Circa 8 Billion people on this planet would have an adverse reaction to other parts of the covid sequence that are not used at present by the western vaccines , given the vast numbers of people its likely that someone somewhere would have an adverse reaction. Its also why I say that no vaccine can be 100% safe or effective as you are relying on the response of each individuals immune system and we are all slightly different, and even an individuals response will vary at different times depending on a range of factors that affect their overall health at the time they need to fight something off. The experts (and I am not one of them) agree that there is still a lot about the immune system that is not yet understood.

 I would agree with Kiwimum that using somebodies vaccination status is not sufficient for international travel and that

 a) international travel should be shut down as much as is possible and

 b) if international travel has to happen then a negative pcr test at the airport should be required , but how do you segregate the passengers before/during/after the tests ?

Like most peple here in the UK, I  have had the AstraZeneca for my first 2 doses and the Pfizer as my booster . I fully accept that there is a risk with any vaccine , but the risk of getting covid without being vaccinated is vastly greater than any risk from a vaccine and assuming that I have not already had covid , its practically a dead cert that I will get it at some point, all I can do is try and make sure I do not get it during a large wave , so that should I be unfortunate enough to need hospital treatment at least I stand a chance of being able to get it.


*Like most people I would prefer to use data from multiple independent peer reviewed papers that have come to the same conclusion and span a few years , but we have to accept that during a pandemic we don't have that luxury and have to go with what we have got.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Hazelpad Quote  Post ReplyReply Direct Link To This Post Posted: December 11 2021 at 5:43pm

Thanks for taking the time for your detailed reply.

Yes I am more worried about the current vaccines from a molecular and cellular immunology point of view. I dont think the Az or the Pfizer is going to turn anyone purple or make them glow in the dark, and I get it's all we have and it had to be developed fast...( actually been trialling for long time) also appreciate the lives they saved...but I think we can do better and find a longer term solution.  

Live attenuated vaccines may be worth a try.  There are modifications that can be done.  (I know Chuck disagrees with this due to coronavirus biology, but that's what science is about opinions). I get that governments are worried.  Recipients shed live virus and then other people say they pick  up the shedded vaccine from surfaces and are therefore being vaccinated against their will.

There are also protein based vaccines  and mucosal or oral vaccines directed at generating immune responses at the mucosal lining.  We need to be investing in other approaches.  

I hear what you say about China and its vaccine efficiency,  but they couldnt over adjuvant their first generation whole viral vaccines  because when they did that with the original SARS 1 back in 2003 it created antibody dependent enhancement.  This was also seen with MERS. They started weaker this time but  by all accounts are  refining and developing second generation covid vaccines.  The point is they are moving forward.

In comparison I am not sure what the UK strategies is.  They are boosting for short term. At the moment I dont even know if our covid boosters are working in a specific manner or if they are just giving the general antiviral responses a boot.  Viral infections work often as natural adjuvant against other viruses.  Maybe by giving flu and covid vaccine together their strategy is to boost each other. 

What carbon says about it not going away now is probably correct.  We have a huge animal reservoir in herd animals that noone knows much about.  It will be mutating in the herds also.  If it came from the wet market from a single host animal then what will spread out from herds of deer etc look like. Mixing and reassortment of zoonotic viruses in herds is not good.

So we need to try other vaccine approaches, think ahead.  We need new therapies and treatment protocols and especially look to repurposing of older drugs.  Not dropping mRNA vaccines but looking beyond.

As I said thanks for your views. I just dont want us to be stuck on a treadmill of vaccine booster after booster with the interval getting shorter and shorter and the public getting more and more disillusioned. So no I dont want to drop the vaccines but I do want to make them better and it can be done as long as we dont stand still. 

Hz x



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