MAP Vaccine Ready for Human Trials - Could be Used for Crohn's

[xeridea]

Thinking out loud here. But how would a vaccine help if you already have CD? Isn't a vaccine intended to help your immune system learn to recognize how to fight a foreign antigen when it first encounters it? What about the case where you're already exposed to the disease, and your immune system just can't figure out how to cope with it? How does the vaccine strengthen your immune system to fight something it has failed to stave off already?

 

[Deleted member 431298]

Thinking out loud here. But how would a vaccine help if you already have CD? Isn't a vaccine intended to help your immune system learn to recognize how to fight a foreign antigen when it first encounters it? What about the case where you're already exposed to the disease, and your immune system just can't figure out how to cope with it? How does the vaccine strengthen your immune system to fight something it has failed to stave off already?

This explanation is copied from the map vaccine website


Mechanism of action: The vaccine is what is called a ‘T-cell’ vaccine. T-cells are a type of white blood cell -an important player in the immune system- in particular, for fighting against organisms that hide INSIDE the body’s cells –like MAP does. Many people are exposed to MAP but most don’t get Crohn’s –Why? Because their T-cells can ‘see’ and destroy MAP. In those who do get Crohn’s, the immune system has a ‘blind spot’ –their T-cells cannot see MAP. The vaccine works by UN-BLINDING the immune system to MAP, reversing the immune dysregulation and programming the body’s own T-cells to seek out and destroy cells containing MAP. For general information, there are two informative videos about T Cells and the immune system below.

 

[JMC]

This explanation is copied from the map vaccine website


Mechanism of action: The vaccine is what is called a ‘T-cell’ vaccine. T-cells are a type of white blood cell -an important player in the immune system- in particular, for fighting against organisms that hide INSIDE the body’s cells –like MAP does. Many people are exposed to MAP but most don’t get Crohn’s –Why? Because their T-cells can ‘see’ and destroy MAP. In those who do get Crohn’s, the immune system has a ‘blind spot’ –their T-cells cannot see MAP. The vaccine works by UN-BLINDING the immune system to MAP, reversing the immune dysregulation and programming the body’s own T-cells to seek out and destroy cells containing MAP. For general information, there are two informative videos about T Cells and the immune system below.

That does not explain whether it would be an effective therapy for people who already have MAP infection rather than just a preventative vaccine. As far as I know, there a very few (possibly none) other examples of a therapeutic T-cell vaccines currently approved for use. Additionally, there haven't been any trials of CMV in cattle with established Johnes disease which might prove this as an effective therapy.

 

[Deleted member 431298]

The claim is that the vaccine works by enhancing immunogenicity (immune response) to the MAP infected cells. I guess that would mean its mechanism of action allows it to work in people that are already infected.
In theory. It will be interesting to follow if it works in practice.

 

[Raggyruby]

Xeridea, yes the vaccine is intended to be both preventative and therapeutic. As OleJ has already answered you can find all of the answers to your questions on the very clear and easy to navigate CMV website.
www.crohnsmapvaccine.com there is further information on www.hav-vaccines.com
There is also a support group on FB if you have further questions Crohn's MAP Vaccine-Fundraising and Support Group.

 

[mtseeg]

I would recommend their Facebook page: https://m.facebook.com/crohnsmapvaccine/?locale2=en_GB

They also have a Twitter page that's regularly updated:

https://twitter.com/CrohnsVaccine

 

[JMC]

The claim is that the vaccine works by enhancing immunogenicity (immune response) to the MAP infected cells.

A reasonably large body of evidence has been published showing that Crohn's patients have an immune deficiency which could impair the handling of intracellular pathogens such as MAP. If that is the case, there must be a high chance that a Crohn's patient would not respond to stimulation by vaccine in the same way that a "healthy" person might. In other words, the vaccine could be effective, yet still not work on the small minority of the population who have Crohn's. The real problem here though is the gap between the claims and experimental evidence - lots of impressive claims are being made with little or no experimental evidence to back it up.

I guess that would mean its mechanism of action allows it to work in people that are already infected.
In theory. It will be interesting to follow if it works in practice.

There have been lots of attempts to create MAP vaccines - just search on PubMed, the majority are targeted at Johnes disease and most (if not all) have failed to produce lasting immunity.

 

[mtseeg]

There are at least two Johne's disease vaccines still on the market: one contains live virus, the other is dead. The latter is sold in the U.S. under the trade name, Mycopar.

https://www.drugs.com/vet/mycopar.html

Also here's a link on the livestock variants.

 

[Crohn2357]

But how would a vaccine help if you already have CD?

The same question can also be directed towards the Qu Biologics SSI trial, though I can't remember if the E. Coli they've been using is an intracellular one or not.

Personally, I'll have a second resection surgery in a few months, and I'm waiting to see what the upcoming announcement of the RHB-104 trial will reveal. I will proceed depending on that announcement.

 

[JMC]

There are at least two Johne's disease vaccines still on the market: one contains live virus, the other is dead. The latter is sold in the U.S. under the trade name, Mycopar.

https://www.drugs.com/vet/mycopar.html

Also here's a link on the livestock variants.

Problem is, they don't work which is why this is still such an active research field

 

[Raggyruby]

Once Jenner have published their findings on phase 1 on healthy volunteers and phase 2 is called, activated, concluded and published as well we will finally have the answers we need.

 

[Deleted member 431298]

Crohn2357- I am sorry the hear you will perhaps need another resection.
Do you usually have elevated calprotectin I wonder? I have read studies that conclude high calprotectin indicate a mycobacterium infection (as I wrote in another thread).

 

[mtseeg]

Problem is, they don't work which is why this is still such an active research field

Interesting. Would you mind posting links to some of the studies indicating these approved vaccines for livestock do not work on the livestock for which they are targeted? The second URL I provided illustrates that they are indeed effective, but I'd like to get a more rounded viewpoint from the scientific community.


From the article:

"Vaccination not only delayed the onset of fecal shedding, but reduced mortality attributed to Johne's disease by 90% in the 200 vaccinated sheep. Silirum is a killed strain of MAP, also related to 316F, that has been tested in Australian cattle. This vaccine has recently been shown to reduce prevalence of clinical disease, as measured by lymph node pathology and fecal culture at slaughter.

Click here for article source

 

[Crohn2357]

Crohn2357- I am sorry the hear you will perhaps need another resection.
Do you usually have elevated calprotectin I wonder? I have read studies that conclude high calprotectin indicate a mycobacterium infection (as I wrote in another thread).

Statistics say the great majority of Crohn's patients will eventually need to undergo at least one surgery during their lifetime.[1]

I have been tested for fecal calprotectin during the early days of my diagnosis, it was used more of an additional diagnostic tool, and the results were always high. I don't know if it indicates the presence of a mycobacterium infection or not. Even if it does, I don't think it would be the only reason for the elevated levels.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976865/pdf/GH-06-587.pdf
http://www.ioibd.org/wp-content/uploads/2012/09/Surgery-and-hsopitaliz-in-Crohn-Gut-2012.pdf
http://www.crohnscolitisfoundation.org/resources/surgery-for-crohns-uc.html

 

[JMC]

Interesting. Would you mind posting links to some of the studies indicating these approved vaccines for livestock do not work on the livestock for which they are targeted? The second URL I provided illustrates that they are indeed effective, but I'd like to get a more rounded viewpoint from the scientific community.


From the article:

Click here for article source

I will dig out the review papers later when I am at a computer at home. To summarise, the problem is that the effect of vaccination is transient - short term improvements fail after a number of months so animals are never cured and is why vaccination (at least LAV) has not eradicated MAP as a problem in the agricultural industry.

 

[JMC]

From July 2016: Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection


A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969274/

 

[Deleted member 431298]

Crohn2357: Even if it does, I don't think it would be the only reason for the elevated levels.

I am curious to know if you have any references to what other causes of Calprotectin rises there are, apart from mycobacteria? I read that NSAID an alcohol could cause slightly elevated levels, but not more than 300 ug/g. According to wikipedia calprotectin has bacteriostatic and fungistatic properties in vitro, but the specific kinds of fungi and bacteria is not mentioned. Also, that these properties come from an ability to sequester manganese and zinc.
Maybe elevated calprotectin is not just a bad thing, but an indication of the body working to get rid of an infection? Zinc supplement is sometimes discussed here as a helpful supplement with CD.

 

[Crohn2357]

According to wikipedia calprotectin has bacteriostatic and fungistatic properties in vitro, but the specific kinds of fungi and bacteria is not mentioned.

Exactly.


Quoting from the Aronofsky's Pi (1998):
"When your mind becomes obsessed with anything, it filters everything else out and you will find that thing everywhere in nature."

I am curious to know if you have any references to what other causes of Calprotectin rises there are, apart from mycobacteria?

Just read a general article about calprotectin in pubmed, you'll see the answer. Calprotectin isn't even specific as a digestive system marker (let alone being specific to immune system's encounter with mycobacterium), so "fecal" calprotectin doesn't have any distinction from elevated levels of calprotectin found in other tissues.

Calprotectin – a Pleiotropic Molecule in Acute and Chronic
Inflammation

 

[Deleted member 431298]

Quoting from the Aronofsky's Pi (1998):
"When your mind becomes obsessed with anything, it filters everything else out and you will find that thing everywhere in nature."

Well, OK. Let us give this topic a rest then.
The thread is about the MAP vaccine anyway.

 

[deedee714]

ok

 

[Crohn2357]

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017


RedHill Biopharma Accelerates RHB-104 Phase III Study in Crohn’s Disease with Top-Line Results Expected Mid-2018

 

[Crohn2357]

The Anti-MAP Therapy Support Group

 

[Guerrero]

Mongersen a new biologic that was presented as a possible new drug for crohn's showed lack of efficacy and his testing has been stopped.

I hope anti map vaccine will work then. We need a cure!

 

[crohninator]

This is what I think about the vaccine. Its actually my last hope.

 

[ronroush7]

Amen to we need a cure.

 

[Deleted member 431298]

Second that.
And until that happens I for one will stay clear of dairy and cow's meat out of precaution.
There is just too much circumstantial evidence around now to ignore the possibility that the MAP present in our food chain is triggering and maybe also perpetuating the inflammation cascade.

A) we know MAP is present in pasteurized milk, cheese, and similar products:

B) we know animals get very sick and die from MAP causing a CD-like condition

C) we know (some of) the CD genes are linked to how the immune system deals with mycobacteria

 

[crohninator]

Problem is quite simple: symptomatic medications work in mild cases (in some cases). They do not work for "real" Crohns. But nevertheless this fact doesn't really care anyone and everybody is pretending an "intact world" where we can "controll the disease" and it has "lost its horror".
NO IT HASN'T LOST ITS HORROR - THIS IS ONLY TRUE FOR PHARMCOMPANIES AND THE MAJORITY OF DOCTORS. You cannot control any disease without treating the cause.

 

[wild_one353]

I thought this study would be important to understanding the relationship with map and the microbiome.
https://www.ncbi.nlm.nih.gov/pubmed/27494144

My stance is that the pathogen map was not as important as the diversity of the microbiome as a whole, and the no cure would be achieved by eradicating map, but restoring the natural diversity of gi microbiome with perhaps a fecal transplant would be a real cure.

 

[Deleted member 431298]

I agree wild_bill - Several factors seems to lead to that conclusion:
- The RedHill study results found that targeting MAP only led to at partial resolution
- Other bacteria/fungei are strongly implicated in the CD cascade (Candida Tropicalis, E.coli, Serratia marcescens)

This picture better match up with the hypothesis that the microbiome is changed and/or has undergone a reduction in diversity, which promotes the presence of many different kinds of pathogens, and results in inflammation.

Reasons? ...
Maybe the stupid binge drinking that is part of western culture (which I for one have had my fair share of right around the time I got CD).
Maybe the "dead" foods we eat / lack of live (fermented) foods
Maybe the food additives and pesticides in our food
Maybe something else, or maybe all of the above

Regardless, it does make alot of sense to start studying how one can best restore and sustain a healthy microbiota - and FMT is a very interesting study object indeed!

 

[wild_one353]

I agree wild_bill - Several factors seems to lead to that conclusion:
- The RedHill study results found that targeting MAP only led to at partial resolution
- Other bacteria/fungei are strongly implicated in the CD cascade (Candida Tropicalis, E.coli, Serratia marcescens)

This picture better match up with the hypothesis that the microbiome is changed and/or has undergone a reduction in diversity, which promotes the presence of many different kinds of pathogens, and results in inflammation.

Reasons? ...
Maybe the stupid binge drinking that is part of western culture (which I for one have had my fair share of right around the time I got CD).
Maybe the "dead" foods we eat / lack of live (fermented) foods
Maybe the food additives and pesticides in our food
Maybe something else, or maybe all of the above

Regardless, it does make alot of sense to start studying how one can best restore and sustain a healthy microbiota - and FMT is a very interesting study object indeed!

According to research: low fiber diet, antibiotics in meat, antibiotics in medical system, vitamin d deficit, emulsifiers that are in most processed foods and all fast food, titanium dioxide food coloring, possibly omega 6 fats. Also factors that stop the restoration of the microbiome like avoiding bacteria too much, we need to be exposed to some degree and build up a diversity but most of this is done when we are born and then breast fed but babies have a knack for putting everything in their mouths so nature makes this pretty easy.

 

[xeridea]

I've been away awhile. Was going crazy before, grasping at straws. Checked recent developments on this site. Same churn. Nothing new. That's disappointing. Nothing seems to have happened for over a year. Damn it! I'll check back again. Next year.

 

[Crohn2357]

Hey, welcome back.

Same churn. Nothing new. That's disappointing. Nothing seems to have happened for over a year.

I am assuming you have seen the results of the RHB-104 trial. Regardless of the results, that study is a significant event in our waiting for a new promising treatment.

I'd be interested in reading your view on the results of it (though it's not published in a journal yet). There's been a big hype surrounding the map hypothesis, a possibility of treating the "cause", and the treatment having at least a significant remission rate distinct from the other treatments.

Check out these links to read about it: https://www.crohnsforum.com/showthread.php?t=82362&page=5
https://www.healingwell.com/community/default.aspx?f=38&m=4044862

 

[Mommabear]

One of my big fears is that if the vaccine fails, many people will believe it will be a reflection on the MAP theory and not simply that the vaccine didn't work (like all of the TB vaccines, which from my count there have been over 20)? Nobody questions TB of course. I hope that I am needlessly worrying and that people know there has never been a therapeutic vaccine that has ever worked except for the recent Hep C one.

 

[rollinstone]

Keep praying guys, there is still hope. As disheartening as it is to hear the rhb104 didn't blow all other meds out of the water, at least it's an option outside of immunosuppressive alternatives. I personally have tremendous hope in the SSI vaccine by qu biologics, and believe that their current 56 week trials will demonstrate a cure.

 

[Mommabear]

My fingers are crossed too rollinstone! I like that they are moving forward, that they have funding (HUGE plus!!!) and that they are looking into why some respond when others take longer to respond or simply don't ... whether a person has been on anti-TNFs. I really like that they have done genetic profiles and can see a pattern with those who have responded. All of those things will help refine this treatment. Plus, they are incredibly nice people!!!