Tuesday, December 08, 2020

FIP vaccines etc

This post is just some random musings about coronavirus vaccines, most clearly in cats. The rest is speculation.  As an introduction here is the abstract-like entry for a book chapter pulled up by Duckduck from 'tinternet. It sums up pretty much what I recall from back in the days when I was a clinician dealing with the horrible disease of Feline Infectious Peritonitis (FIP), derived from complications of Feline Enteric Coronavirus infection. No author is stated but if I was an editor looking to have a chapter written about FIP I would, without any doubt, send the request to Niels Pedersen, who authored this (very long and involved) review:

A review of feline infectious peritonitis virus infection: 1963–2008

The chapter abstract summarises the interesting bits of the Pedersen's review nicely:


Coronaviridae

In Fenner's Veterinary Virology (Fifth Edition), 2017

Immunity, Prevention, and Control

Feline infectious peritonitis is not controlled easily; control requires the elimination of the virus from the local environment, whether this is the household or the cattery. This requires a high level of hygiene, strict quarantine, and immunoprophylactic measures. Because kittens acquire the infection from their queens, early weaning programs have also been used in attempts to interrupt virus transmission.

The development of a safe and highly effective vaccine remains elusive, even with the availability of bioengineering approaches. The only commercially available feline infectious peritonitis vaccine contains a temperature-sensitive mutant virus, based on a serotype II virus. The vaccine is applied to the nasal mucosa to reduce virus replication and antibody formation. Under these conditions, a cellular immune response is favored, and some protection putatively is achieved. Vaccination of infected, seropositive adult cats is not effective. In addition, experimental challenge of vaccinated cats has resulted in “early death” due to feline infectious peritonitis in some cases.

A broad spectrum coronavirus protease inhibitor drug has recently shown considerable therapeutic efficacy for treatment of cats with feline infectious peritonitis, a finding that suggests the disease might in the future be treated with antiviral drugs.



What is clear from FIP vaccination is that antibody production (or the administration of hyperimmune serum or pure IgG antibodies) in the absence of a cell mediated immune response, is lethal on challenge of kittens with a field strain of FIP virus. The serum is harmless, the IgG is harmless, the vaccine is harmless. What matters is how the disease progresses when field virus meets the antibody replete host. The effect of a vaccinia virus vector vaccine was described here (you only really need to read the title, it says it all):

Early Death after Feline Infectious Peritonitis Virus Challenge due to Recombinant Vaccinia Virus Immunization

which could reasonably be described as a bit of a booboo.

To summarise: Vaccines which stimulate antibody production without stimulating cell mediated immunity are a problem. This is Antibody Derived Enhancement. It's real. It has plagued (no pun intended) certain vaccines, obvious for FIP but Dengue Fever vaccine is a similar but non-related example in humans.

I'll leave FIP alone now except for adding that work with the reagent GS-441524 suggests that FIP is no longer the invariable death sentence which it was two or three years ago. People who have worked clinically with FIP, or lost cats to FIP, will understand the awe that this drug inspires. I hope it gets used sensibly.

Anyhoo.

I was listening to Radio 4's The Life Scientific which featured an interview with Prof Sarah Gilbert from Oxford, heavily involved in the development of an adenovirus delivered vaccine for protection of humans against SARS-CoV-2.

Apart from how genuine and extremely bright she is the main thing I recall is her comment that she was very pleased that the vaccine she was developing produced a robust cell mediated immune response in additions to stimulating antibody production.

This is excellent and is all that you could ask of a vaccine where antibodies are frequently high and ineffective well before admission of patients destined to die of COVID-19 complications in the ITU.

It looks like cell mediated immunity is what matters. That antibodies are non protective is also suggested by the extremely poor results using antibody rich serum from recovered patients to treat unwell patients with COVID-19. There is no suggestion that serum treatment did direct harm, just it didn't do much good.

So the major question this poses is how much good the vaccine might do in patients who are going to become ill with COVID-19 in the future. It is not an unbelievable stretch of fantasy to suggest that the defining characteristic of people who are going to go on to become seriously unwell after exposure to SARS-CoV-2 might just be those are the ones who are unable to mount an effective cell mediated immune response.

How well might the T cells of an 80 year old, morbidly obese diabetic respond to the vaccine, assuming they are not very likely to respond to the field virus?

We can but hope that if they do fail to develop cell mediated immunity then at least their antibody response (which will still happen) does no harm. And we can hope that cell mediated immunity response has been carefully assessed in the population to which to a COVID-19 vaccine is being rolled out as of today in the UK... 

Otherwise it's a bit of an experiment on many, many people's grannies.

Peter

41 comments:

Tucker Goodrich said...

I brought this to Derek Lowe's attention back in April.

“Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins”

He's been doing some pretty in-depth vaccine reviews since then.

"There was also no sign of antibody-dependent enhancement in any of the treated animals."

Or any of the human subjects.

So happily this appears to be more of a theoretical risk, than a deal breaker.

Eric said...

Very interesting, thank you. For me, this came right after seeing this:
https://www.theguardian.com/world/2020/dec/08/covid-mixed-vaccine-trial-likely-to-begin-in-uk-next-month

So the vector vaccine might rely mostly on stimulating T-cell response. This would explain why it was not so effective in older people. I got this much.

Both mRNA vaccines mainly stimulate antibody production which may not be all that useful. If that is the case, why is it then that they are highly effective in everybody and seems to generate long lasting immunity? After all, there are no cells to attack for the T-cells. This is what still puzzles me.

As a layman, my main concern would be that in a person that had (undetected?) immunity already, mRNA instructing the body's cells to churn out spike proteins could trigger an outsize immune reaction, but apparently, this is not the case:
https://nyti.ms/37FsHuP

(scroll down to:
I had Covid. Is it safe for me to get a vaccine? If so, when could I get one?
It’s safe, and probably even beneficial, for anyone who has had Covid to get the vaccine at some point, experts said.)

Eric said...

Another new thing for me:

https://www.youtube.com/watch?v=MKNavonhXyk

18 Minutes into the video, Dr. Gilbert talks about antibodies, at least in low concentrations, making it easier for the virus to get into cells.

Eric said...

Let me type that from the slide - it's about lessons from CoV-1 = SARS.

SARS-CoV: immunopathology after vaccination and viral callenge in some preclinical studies
- vaccinated animals exibited greater severity of infection than the controls.
- Th2-skewed immune response resulting in eosinopil infiltration of the lungs
- antibody-dependet enhancement of infection
whereby the presence of non-neutralising antibodies resulted in entry of SARS-COV into haematopoietic cells via an FcgammaR dependent and ACE2- ph-cysteine protease independetn pathway.


(Greek to me)

Peter said...

Tucker, that would be excellent.

Eric, I'm not sure how much any of these things have been looked at critically without following Tucker's leads. But ultimately, we're in the process now here in the UK so I'm hoping it all goes well.

The other aspect I expect to come out (and it might not) is that I expect none of the vaccines to prevent transmission. This seems to be very common for injected vaccines against respiratory pathogens. This need to vaccine to be highly effective at preventing sever disease in the compromised elderly. It might.

FIP was a bruising condition to (fail to) manage. I'm glad the kiddie vets have a tool which helps, even if it is a nightmare to get hold of.

Peter

Gyan said...

I don't understand why a person who has recovered from a covid infection should be vaccinated. He presumably has all the antibodies and cell-mediated immune response. What is the point of artificially provoking a response that is actually existent naturally.

Unknown said...

Hi Peter, as you enjoyed the Dr Rich Breeze talk I thought you might like this one. It covers antibody, immunity and vaccinations from the guy at Siemens who developed their assay - the only one to hit the MHRA's TPP assessed by PHE: https://www.meliohealth.co.uk/issue/covid-antibody-testing-immunity-and-vaccinations-with-james-freeman

Peter said...

Hi Gyan, my work colleagues are generally middle class, skinny women with school age kids. They have watched their friends, of similar status, have COVID-19 with convincing symptoms and even a positive PCR test result, for what that is worth. None of them are exactly keen on getting vaccinated! That's without any influence from working with me. It's a common sentiment among other non-comorbid people I've met... I'm keen my wife's step-father continues to shield as he has certain significant risk factors. Here in East Anglia we had a mild first wave so are playing catch-up at the moment, so I feel we will be late getting to herd immunity to protect him. I guess he will have the vaccine and be glad of it.

Getting vaccinated when you are certain you have recovered from field infection is utterly, utterly stupid. Prior SARS infection recovery from 17 years ago appears to confer immunity to COVID-19 today.

Plus, never forget Swine Flu! Had you forgotten? Me too.

Peter

Peter said...

Thanks Unknown, I'll give it a watch. Dr Breeze's chat was excellent.

Peter

Peter said...

Hi Unknown,

Had a listen. I struggle with his ideas slightly. Towards the end comes the concept that having recovered well the field virus may not stop you carrying, excreting and infecting others with the virus. This is an interesting idea and suggests that the human immune system is ineffective at stopping transmission. Which, in general, it's not (there are exceptions).

I can completely accept that a vaccine which produces a combination of systemic IgG (plus systemic cell mediated immunity) would leave your mucous membranes wide open to carrying the virus until such a time as you mount a surface IgA response within your airway. This will not come from an injected vaccine, which may well not get in to the airway (though adenovirus vectored vaccines might, dunno for sure on that one).

Obviously if you are vaccinated and then exposed to the virulent virus you will, in all probability, develop effective pharyngeal surface IgA immunity without becoming unwell making you less of a vector, but that's not easy to test for.

Having neutralising IgG in your blood will do nothing to a virus particle in your pharynx. IgA is designed to do this. You get IgA from direct contact of pharyngeal membranes with virus (or vaccine if it's an intranasal vaccine). I doubt a systemic vaccine will ever do as good a job as the field virus does on the nasal mucosa.

Ultimately, if you are a morbidly obese diabetic you are going to grab the vaccine with both hands and hope it works for you personally, even if it doesn't stop you transmitting the virus to others...

Peter

John said...

HI Peter...Don't know how to get a hold of you Sorry to disturb this thread... IVERMECTIN looks like the answer to COVID?

https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdf


Lots of info coming out but I think Pig Pharma not happy...as they are not happy about ARTEMISININ.
Have followed/used this for several years and keep my 6 puppers healthy....this post starts w Artemisinin which has killed my leukemia and prostate issues...I'm 75 and have read you for a few years...live in Belize...an old Pole familiar w K...further down in post he addresses IVERMECTIN...I like this guy too...CHEERS! JOHN MAZURA JMAZURA.BELIZE@PROTONMAIL.COM

https://jeffreydachmd.com/2016/02/artemisinin-our-ultimate-cancer-weapon-a-gift-from-china/

Eric said...

Peter, very interesting information that you need IgA to get rid of the virus on mucous membranes.

So would it be a good idea to combine the jab with a spray? Have not seen that reported.

I also wonder if this the reason we are seeing cases go through the roof in places that should by all rights have herd immunity:
- 48% of Tokyo commuters having had antibodies by August
- no Covid cases in two months in Stockholm hospital by August as reported by Dr. Sebastian Rusworth
- at least 110 million people (yes!) in the UK having had the virus if one calculates backwards from fatalities to infections

On the other hand, I would assume that a reinfection of the mucous membranes can trigger a PCR or antibody test but would usually not result in a severe case. But what we are seeing is a huge increase in ICU occupancy and deaths almost everywhere. Something does not add up. Anybody for hypotheses?

About the hesitany to get vaccinated if skinny and healthy, there are just too many cases of people without risk factors getting very sick. And I have read accounts from healthy people in their 30s and 40s loosing their sense of smell and taste for months. While not life threatening, it seems to be quite an ordeal and may not be good for one's mental health.

Unknown said...

Thanks for the food for thought on the podcast, Peter. I got the impression he was extremely cautious about the words he used, especially as his company produces the test. Though a similar point was made by Adrian Hayday, the Immunologist, in a podcast that he did with Melio.

Peter said...

Unknown, I think what he is offering is of great interest to people wondering if a vaccine may or may not have produced a protective effect. My assumption is that any antibody, of any family, resulting after recovery from field virus exposure is a surrogate for your having made a completely effective response, ie evidence you have been exposed without being ill suggest that you have a competent cell mediated immune response as well as an antibody response. For this information a messy yes/no would be fully adequate, if carefully set up to minimise false positives. And false negatives too, although it's the false positive which could get you killed!

Peter

Peter said...

Hi Eric,

Sorry to be anglo-centric but ICNARC report that ICU occupancy for October is absolutely on the mean of the last four October values. We may get November's today but it's not on the website yet. ICU occupancy has been below that for previous years for June, July, August and September this year. The trend is now upwards, so November might be just above the values from the previous four years. Overall we are certainly not overwhelmed in the UK.

Wild speculation. Respiratory viruses are seasonal. What if countries which got caught badly before the end of their winter season are doing OK now, just some catch up (like I'm expecting us to do here in East Anglia). Countries which missed out on the first wave may have much, much more catching up to do.

Now, if we knew what made made influenza etc seasonal then we would be on to something.

Of course here in the UK the health service has been pretty badly damaged by the lockdowns and people's fear of going to hospital. You are probably aware that doctor's strikes (there have been quite a few) ALWAYS result in a marked fall in all cause mortality, which reverses immediately on ending the strike.

The COVID difference is that A&E has always been maintained throughout doctor's strikes. In COVID people stayed at home and just died, about 1000 per week since the start of April, according to the UK Office of National Statistics. Of course people dying at home don't end up in the ICU!

Peter

Eric said...

Peter, did you really mean to write this?
You are probably aware that doctor's strikes (there have been quite a few) ALWAYS result in a marked fall in all cause mortality, which reverses immediately on ending the strike.

I may have strong reservations about doctors but I didn't think they were this bad for our health :)

Bob said...

Hi, Eric,

I've read this is also true of police strikes and crime, at least in the USA. The reason given is that police are under certain constraints when dealing with suspects (yes, I realize it's controversial how constrained police sometimes are), but private citizens are not so constrained, and crooks know it. So they're less likely to break into someone's abode and deal with a furious and frightened resident who can't call the on-strike cops.

Just another reminder things don't always work the way they're "supposed" to.

Peter said...

Eric,

It is simple fact. Elective procedures benefit well being but are never risk free. They stop during Drs strikes.

https://www.sciencedirect.com/science/article/abs/pii/S0277953608005066

COVID restrictions are very different to a Drs strike.

ICU occupancy for November is out now, ICNARC have accurate, up to date data until Dec 2nd. We are about 600 case occupancy in ICU above average for Nov (which is around 2,800 most years) but admission rate is currently dropping rapidly, certainly faster than it rose. Obviously not everyone leaves the ICU alive but falling admission rates are clearly excellent... The incomplete data for the following few days suggests an on going fall in admissions through early December. From

https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports

using the link in the first section to "COVID-19 report".

My feeling is the UK was unlucky in Spring and is doing ok-ish now. Germany looks to be the converse... As Tegnell has said, we will have to wait a year or two to see how things really work out.

Peter

Peter said...

Thanks Bob, hadn't read about police strikes, interesting. The Dr strikes phenomenon I read about back in the late 70s. It was well established then. Yea gods, did I read all sorts of stuff before 'tinternet.

Peter

Eric said...

Peter, it is always interesting what I can learn here. It would be interesting to see if the gap is fully made up of deadly outcomes of elective procedures. Maybe it is just people staying away from GPs and not getting prescribed what I call elective or ill-advised medicines.

Just looking at Covid deaths, the UK, France, and Germany are not too different, it is just that they are coming from different places. It with widespread immunity that should be there in the UK and France, I find it surprising that deaths are still that high.

The UK might be looking somewhat better right now because of increasing immunity (my guess was that this should have been achieved by summer, but somehow it wasn't) or because it entered a serious second lockdown much earlier. Germany is getting serious just now, and they are still talking about keeping schools and shops open until right before Xmas.

Re ICU-occupancy, I doubt you can compare countries. The UK always had a low ICU capacity (which may be a good thing for various reasons), so a given severity of Covid might land you in ICU in Germany, but not the UK.

This graph (at the very bottom of the article) has ICU occupancy over time in Germany. Orange is Covid without ventilation, brown is Covid with ventilation. Their total is around 4000 now. Overall capacity has been going down since November for various reasons:
- staff being sick
- more staff needed to care vor Covid than for other patients
- elective procedures limited, hence less need for reserve capacity
- hospitals trying to pressure politcs into more action

Eric said...

sorry, here's the link:
https://www.swr.de/swraktuell/so-wirkt-der-teil-lockdown-100.html

Peter said...

Eric, the same has been said for current hospitalisations for COVID in the UK, the criteria for admission are lower now than they were in the spring because there is no overwhelming problem at the moment. At least that's Carl Heneghan's view. Given the choice between trusting someone specialised in evidence based medicine vs Matt Hancock I feel a tendency towards someone who is not a pathological liar... Easy choice really!

Peter

Bob said...

"...the criteria for admission are lower now than they were in the spring because there is no overwhelming problem at the moment."

I wonder if this is true in California as well. We're "locked down" again more severely than ever (apparently LA Mayor Garcetti decreed "no non-essential walking" -- oh, brother!) mostly over declining ICU capacity.

It's easy to think of some variables as fixed in nature, like hospital admissions. But, if Heneghan is right, some variables are, um, variable (I guess like PCR test thermal cycles). Makes it impossible to do apples-to-apple comparisons.

Eric said...

Bob, I can imagine the thing about criminals being more careful during police strikes to be true in the US, and even barely so. Many people keep guns at home and may used them against an intruder with few restrictions. They do use them even when the police are not on strike because "it's their right" and they will be quicker than any patrol. Still, burglary rates are high on an international scale.

In countries with fewer guns at home and more restrictions on their use in self-defense, even that explanation falls apart.

Eric said...

Peter,

are your work colleagues reserved about getting vaccinated because they think they don't need it or because they are sceptical about side effects or long term damage? Apparently, a survey by the German vaccination council (I suppose our equivalent to SAGE when it comes to vaccines) found out that medical personal are more reserved than the average population about getting vaccinated. No explanation was given, but Karl Lauterbach (a very vocal MP and former epidemiologist) tweeted immedeately that this was driven by a false sense of security (PPE, and doctors appear to feel invincible in general) and that they should reconsider both their personal risk, the risk of becoming spreaders, of not being able to care for their patients, and about setting an example. Full guilt assault!

But I am curious if reservations about efficacy and safety do exist. What do your colleages say?

Eric said...

Peter,

I typed this up yesterday but somehow it didn't get posted. I had not previously seen the low ICU occupancy rate for Covid in the UK:
https://www.thesun.co.uk/news/13219465/covid-patients-hospital-still-rising-icu-admissions-falling/

So I can see why you say the severity is probably not as bad in the UK as it is elsewhere.

So we have < 200 in ICU in England (not UK, so 56 million inhabitants) out of adult ICU capacity of about 4200. Are pretty much all of them being ventilated?

In Germany (pop 83 million) we have 4000 in ICU, half of them ventilated, out of a total capacity of currently due to staff shortages 27,000. It may simply be that doctors, justly or not, are taking the decision to transfer to ICU more lightly.

When we look at infection rates, the UK and Germany have been at give or take 20,000 per day for the last four weeks, and deaths by Covid are eerily similar at 430 resp. 440. France, through a long lockdown, has infections down to 10,000 and deaths are lagging but now at 370 (used to be in 500-600 territory). Spain, which was in a bad place in September, is now down to 6,600 infections and 200 deaths.

Sweden is now at 5,900 infections / day and 64 deaths. At the same time, the Stockholm region has 100% ICU occupancy now and they are having to transfer patients to Finland and Norway. The reason they are seeing few deaths (even compared to Spain which has the same average infection rate for the past week) is that they have been trending up whereas everyone else had plataued (UK, Germany) or was receding (France, Spain).

Italy is at 17,000 infections and 650 deaths. They had their peak infections about two weeks ago so hopefully deaths are going to be much lower in two weeks time.


The picture that I see here is that infection rates seem to matter, pandemic history and ICU capacity not so much.

Now, excess mortality (available for most countries out to mid November) is a different story:
Significant second peaks in Spain, France, Italy, Switzerland, Austria, the Netherlands, Portugal and a triple peak in Belgium. Very little in the UK, nothing in Germany, Sweden. Italy is only reporting into August. This, again, supports your take that the UK is doing okish.

It will be interesting to look at December numbers when they are out.

Eric said...

forgot the link again:
https://www.spiegel.de/wissenschaft/medizin/coronavirus-infizierte-genesene-tote-alle-live-daten-a-242d71d5-554b-47b6-969a-cd920e8821f1

Worldwide numbers (one week average) is the first data insert, excess mortality the third.

Eric said...

And while I am generaly in favor of controlling infections, I think they have gone overboard in our state. They imposed an 8 pm to 5 am curfew on Saturday but left shops and schools open (until Tuesday when the nationwide shutdown starts). You can still meet with 5 people from two different households but if you don't get home by 8, you have to stay the night. Now if they are concerned about private partying, is it better if folks stay and probably continue partying?

Peter said...

Re vaccination, hard to say. It's not just me because people tell me it is a general impression, common in people who don't know me at all.

BTW Have you ever heard of "Feline adjuvant associated sarcoma"? It is supposed to be very rare. I have operated on two staff cats for this in the last 5 years and on a number of other cats too. This is brutal, aggressive, radical surgery with a guarded prognosis. Nurses who have lost cats to this and subsequently had to nurse client owned cats through the same op tend to be somewhat cautious about vaccines.

More generally people who have tested PCR positive and been ill have, in their demographic, been trivially unwell. One coughed for three days, one lost sense of smell for one day. They kept their kids (no symptoms, not tested) off of school for 10 days.

None of the people I work with are overweight, let alone morbidly obese, so this may slew attitudes.

I also guess that even people who voted for Bojo did it for reasons other than any sort of trust in him. They wanted Brexit, Bojo is the tool. I doubt anyone is foolish enough to trust him on anything.

Obviously all politicians are bent, just some hide it better than others. In some ways you do have to admire Bojo. He makes no effort to hide his character. You get exactly what it says on the can.

Peter

Eric said...

Peter, no I hadn't. Is this associated with any particular adjuvant? With most conventional human vaccines beng adjuvant enhanced (as is the AstraZeneca?), one would think that if this were an issue with humans, one would have heard about it. mRNA does without, but then it is the new kid on the block, which carries risks of its own.

I am reasonably sure we've had it (two teenage kids in school, my wife communting by train daily until March, myself travelling to Newcastle, Amsterdam and all over Germany and mingling with people who had just returned from Silcon Valley and Asia in late February, early March. Still there is no was to be sure now, and longer lasting lost of smell or gratitous vascular disease would be deal breakers for me.

Does Boris even know what it says on his tin?

As for our state, we have a green (but somewhat conservative leaning MP) and a conservative coalition partner with a conservative education secretary who sometimes reminds me of Miss Umbridge. It is also the homeland of liberalism in Germany (going back to the failed revolutions of 1830 and 1849). Why introduce a curfew that makes little sense when you think about it before seriously enforcing mask rules in public schools or closing retail and schools?

Eric said...

https://en.wikipedia.org/wiki/Vaccine-associated_sarcoma

Oh boy! And dogs and ferrets can get it, too. I was never happy about aluminum salts in human vaccines, but this is something else. Is there reason to believe humans are fundamentally different from those carnivores?

Re: personal experience, this can be treacherous. I know of plenty of people that have had it but with the exception of one kid in my daughter's class, I haven't met any of these. But a colleage already had four people in his extended family die of the virus. And I know of a colleague (whom I actually knew in person) dying of an embolism in her early forties, but don't know if she had had Covid before. If you go by personal acauaintes only in a reasonably healthy demographic, chances are there isn't anybody with serious damage.

Eric said...

https://oem.bmj.com/content/early/2020/12/01/oemed-2020-106731

7x higher risk of severe covid for medical staff. Doesn't talk about vets, though.

Peter said...

There is no syndrome like Feline Adjuvant Associated Sarcoma in any other species (that I know of). I only mention it because it does nothing to enhance anyone's confidence in adverse reaction honesty from vaccine manufacturers. Personally I buy a non-adjuvated vaccine for my cats and only give it every three years rather than annually. The sarcoma is actually associated with any chronic trauma location, microchips have also triggered it. But the adjuvant makes a spectacular image in the centre of a highly aggressive sarcoma when viewed by the pathologist. It's the common cause. It's a common tumour. The 1 in 10,000 cited in the literature is bollocks.

Peter

Peter said...

I think developing metabolic syndrome is a marker of having qualified as a medic, a sort of badge of honour. I also think three weeks of sleep deprivation under conditions of extreme stress with physical and mental exhaustion will make it a damned sight worse. I think subsisting on Snicker bars from a junk food dispenser because you're too tired to go to the canteen (if you are allowed there from the COVID wards) for a lovely low fat, high carb HeartHealthy pasta dish is only slightly the worse of two evils.

Just opinion. I have no evidence.

Peter

Peter said...

Interesting. Never seen an injection site sarcoma in a dog, at least not that I recognised (and they're not hard to spot!).

Peter

cavenewt said...

Eric, thanks for the Wikipedia link, interesting. Learning about aluminum adjuvants in some vaccines finally pushed me over the edge to stop getting the flu shot every year, around 2014. Reinforced by the fact that I just don't get sick anymore, since I stopped eating carbs in 2010.

Adjuvants are used in vaccinations because they increase inflammation which increases the immune response, essentially making manufacturing cheaper—excuse me, sorry, I meant more efficient—because you can dilute your vaccine. So it makes sense that adjuvants can be toxic substances like aluminum.

Apparently they're still using aluminum adjuvants in some vaccines, which is mentioned in this CDC article. Another adjuvant that is commonly used these days is squalene, most of which is derived from shark livers. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/influenza-h5n1-virus-monovalent-vaccine-adjuvanted-manufactured-id-biomedical-corporation-questions

I did read an article that said no excess sharks will be killed in service of making covid-19 vaccine. Yeah, right.

Peter said "Personally I buy a non-adjuvated vaccine for my cats..." I wonder if such thing is available for us mere civilians here in the US. I do have a question about the feline leukemia vaccine. It's given as an example of another type of vaccine that can cause the sarcomas; do they not give it as a nasal spray anymore? My cat's about five years past due on all her shots. Are nasal spray vaccines also adjuvanted, and have they ever been suspected to cause similar side effects?

Peter said...

cave, intranasal vaccines are usually aimed at respiratory pathogens, they're not adjuvated. The only one for cats which showed up briefly in the UK many years ago was aimed at bordatella infection but it never really took off. Of no obvious clinical benefit really. The currently used canine intranasal is aimed at bordatella too but has a marketing lever because many kennels will not accept non vaccinated dogs. There are many other causes of cough in kennelled dogs but bordatella is a significant one.

The choice in parenteral vaccines is adjuvated vs live virus. Both have their problems. Live vaccines carry the risk of live viral contaminants, such as SV40 in the human live polio vaccines. ISFM is currently recommending FeLV vaccine as a primary course, booster at a year and then every third year after that. When I was a clinician I would discuss discontinuing FeLV vacc after about 12y of age and advised stopping it after about 15y. Susceptibility drops with age and sarcoma risk increases with number of doses was my logic. For fully indoor cats I would always discuss, and advise, avoiding the vaccine. Unless there were very specific reasons for which the fully indoor cat might still be at risk.

The main feline respiratory virus vaccines are all live injected vaccines and I have advised clients for decades that they do not stop infection, merely reduce illness.

Peter

Passthecream said...

"I did read an article that said no excess sharks will be killed in service of making covid-19 vaccine."

I did hear that horshoe crabs might be driven to extinction though. Their blood is harvested to make some important, irreplaceable lab reagent.

cavenewt said...

That's very sad about the horshoe crabs, if true. You think they'd try to find a better way.

I said above that squalene was an adjuvant. Apparently not. It's just one of the lipids they use to encapsulate the payload.

I found a range of opinions on whether mRNA vaccines need adjuvants or not. It's generally agreed that they don't need *as much*. Some articles outright say they're self-adjuvanting, others say an adjuvant "may" be helpful.

Tucker Goodrich said...

Lowe did an update. tl;dr: no sign of it so far in the current vaccine candidates.

"Antibody-Dependent Enhancement"

https://blogs.sciencemag.org/pipeline/archives/2020/12/18/antibody-dependent-enhancement

Peter said...

Good read Tucker. The drive to convert feline enteric coronavirus in to feline infectious peritonitis virus is intimately linked to a mutation which allows it to infect macrophages, which drive the formation of lethal solid granulomata or immune mediated vasculitis. This mutation takes time in the FIP model and prompt clearance of the virus (as is usual in field infection) is what seems to be protective against this development. I have to say that this post is completely based on thinking around FIP and reading Lowe has expanded my knowledge base about ADE a great deal. The on going, never ending war between host and pathogen is fascinating. Not just viral either.

Ta

Peter