The data described by Naser et al in this recent paper suggest that genetic polymorphisms may play vital role in T-cell regulation, susceptibility to mycobacteria and ultimately response to treatment. This is the first study to report the detection of MAP DNA in the blood of RA patients; further studies are needed using larger number of samples.

 

https://www.frontiersin.org/articles/10.3389/fcimb.2018.00011/abstract

 

“Current vaccines cannot distinguish vaccinated from infected animals, thus compromising JD diagnostic tests (80), and strain 316F was generated in the 1920s by random attenuation procedures …. that are only now being investigated (81). In the final analysis, a vaccine of high efficacy is needed to significantly control JD (82).”

https://www.frontiersin.org/articles/10.3389/fvets.2017.00187/full

Collins et al (Nov 2017)

 

This excellent paper lends weight to the idea that pathogens cause many insidious diseases, in this case Multiple Sclerosis. We recommend you read the whole paper, but if you are short on time, John Kurtzke’s conclusion is as follows:

Is there any way to consolidate in some sensible fashion this mass of material I have gleaned over the last 60 years? How could primary multiple sclerosis affection be the cause of multiple sclerosis? One possible formulation that supports my hypothesis at this point follows as a series of arbitrary and dogmatic statements, each of which could well be presented as questions, but all of which together explain to me this illness:

  • Primary multiple sclerosis affection is a specific, persistent gastrointestinal infection, presumably viral, and is the initial stage of clinical multiple sclerosis in a few of those infected;
  • Susceptibility to primary multiple sclerosis affection is mostly limited to ∼11–45 years of age, but transmissibility ends after ∼25–30 years of age;
  • In natives of high risk multiple sclerosis areas, primary multiple sclerosis affection acquisition requires ∼4 years of exposure from the age of 11 and is likely to be asymptomatic;
  • Immigrants from lower to high risk areas require ∼3 years of exposure from age 11 for acquisition, also likely asymptomatic;
  • In virgin populations, primary multiple sclerosis affection infection begins as an acute illness acquired by persons of all ages (cf. measles), but persistent primary multiple sclerosis affection requires ∼2 years of exposure, also from the age of ∼11–45;
  • Early after acquisition the primary multiple sclerosis affection agent in some of the affected patients starts to cross the gut wall into regional lymph nodes, from which a further fraction then begins a lifelong invasion of the CNS through the blood stream and CSF (cf. acute poliomyelitis); and
  • This is a testable hypothesis.

https://academic.oup.com/brain/article/136/9/2904/293020/Epidemiology-in-multiple-sclerosis-a-pilgrim-s

Howdy All-

So it’s come to my attention that there are some folks very interested in the current Crohn’s vaccine trial happening in Oxford and, being a trial participant, I might be able to shed some light what is going on. I’ll do my best to give you what information that I can and not compromise anything without knowing it. So let’s start with some basic info about me-
I’m a white American (now also British!) male, 41 years old. 100kg and 187cm – okay you probably didn’t need to know all that, but hey I feel I’m on display so why not give that info for those wondering.
As for my background, I am a PhD researcher currently working at the University of Oxford with the very group [Clinical Biomanufacturing Facility] who has physically made this vaccine that I recently got injected with [though when I signed up to do this trial, I didn’t know they had made the vaccine]. Prior to working with these folks, my research focus was on vaccines and rare diseases with focus on gene therapy of a few different types. But none of my research has been with Crohn’s or those associated with Crohn’s.

I do not have the disease (obviously) but my brother does. I have always kept him informed of the latest research and tried my best to translate it for him at a non-scientist level. And I made promise to him if I could ever help with the research in the disease in some way or another I would. So as soon as I found out about this study I got myself signed up and purposely requested to be one of the folks at the highest dosage level. I figured if I could tolerate it, he’d have a great chance too.

So what goes on as a volunteer for the vaccine? This is a lot simpler than most people think. You initially go through a quick screening process that does a quick health check [blood pressure, temperature, weight, height] and a blood draw. They also contacted my GP to make sure I had no medical history [i.e. bleeding disorders, etc] that would exclude me. They also had to check on my previous vaccines and any other trials I had participated in, in the past. I have participated in multiple vaccine trials in the past [if you work in vaccines, you have to support other folks however you can] so we had to make sure that I had not been vaccinated with the same type of adenovirus in the past, or at least not within the last 6 months. They felt that if at least 6 months had passed, it should not affect the vaccine even if the same base adenovirus was being used. Now there was one extra step I had to go through because I work within the Jenner institute, I had to go through and extra interview to prove no conflicts of interest. And before I fully enrolled I was also given a document explaining everything that was going to happen during this trial, the virus used, why the trial was taking place and how my info & biological materials were to be used.
Because this is a phase I trial for safety/tolerance the wait between this initial check and when I was finally vaccinated was much longer than normal, almost 3 months. I asked about this and they said it was because of the trial design.

No special prep was need to be vaccinated. On the day of vaccination I had my blood pressure and temperature checked, along with a new blood draw. I then went out to the waiting room while they prepped the vaccine. I was then called back and injected intramuscularly [they were also kind enough to ask which arm I preferred- I chose my non-dominant arm]. I then went back to the waiting room for a 1 hour waiting period to make sure I had no sudden immune response to the vaccine. They did two checks during that time. One check at 30 minutes, looked at the vaccine site and checked my temperature. Then at the 1 hour mark they checked my blood pressure along with the temp and injection site. I was given a card that had emergency info on it if I felt extremely ill and told what to do in case of serious side effects (i.e. how to deal with hospitals and when to call them). I was also given an electronic diary that I had write in each night. I had to return 24 hours later, then at 72 hours, 7 days, and 14 days. I still have to return at 28 days, 56 days, then 365 days. I find these time points interesting as I’m used to having a 3 month and/or 6 month check, not a 2 month check. But every trial is different and there are reasons behind this.
As for the scheduled visits, it is a simple process. With the exception of day 14, blood was drawn at each visit, along with a temperature check, and blood pressure. The injection site was inspected and measured for redness during the first 7 days. And we went over my diary entries. Most visits take less than 15 minutes.
I have been informed that I will have blood drawn again at day 28 and day 56 and I suspect at 1 year.
As for me, I’m not your everyday volunteer. I have been through 5 previous vaccine trials over the last 16 years [Small Pox, Anthrax, Bird Flu, Malaria, & RSV]. Plus my passion is vaccines, hence why I work with them. That said though, I’m still cautious. I make sure I understand the type of study I’m going into. I’m not normally willing to go into a study where there is a true risk to myself or my family [the exception was of small pox back in 2001; technically I could have infected others, including my wife, due to the nature of that vaccine]. And any study I do, I always ask would I be fine with my wife or friends participating in it. If not, then I wouldn’t participate. This was the first time I was willing to take a risk with a truly unknown vaccine as it was for my brother and a potential cure/relief for his Crohn’s. And then I also discovered my co-workers made the vaccine, so I knew who I could pick on if I got really sick.

I hope this, umm, ‘short’ bit of info has helped some folks, but I should state that I only know what any volunteer would know. Meaning I’m not privy to any info about how the vaccine is going in anyone else or what they are specifically looking for in the blood [obviously antibodies, but what levels and types, no clue].
Cheers,
Tom

‘Latently adapted’ organisms can persist for years or decades until reactivation occurs due to a variety of factors including waning of immuno-surveillance.

“These results demonstrate that MAP is capable of adaptation to NRP [non replicating persistence] similar to that observed for MTB with differential susceptibility to antibiotics under aerobic versus anaerobic conditions. Such findings have significant implications for our understanding of the pathogenesis of MAP in vivo and the treatment of CD should this organism be established as the causative agent.”

“Mycobacterium avium paratuberculosis is zoonotic. It is possible that MAP infects an individual, and an immune response ensues that limits but does not eradicate the organism, leaving it to survive in macrophages and other reticuloendothelial cells. For reasons that are unclear, this latent infection responds to a “triggering event” that leads to disease. This is analogous to Mycobacterium tuberculosis, which causes a latent infection; the infection activates when immune status changes in the host.”

Oken et al (May 2017)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493936/

 

CURED not managed Profile Pictures To celebrate World IBD Day 2017, we are relaunching our ‘Cured, Not Managed’ images. Please download, wear and share with pride! The slogan was created by our late graphic designer Joanna Cardwell-Fox in 2014 and the image re-imagined for 2017 by Julie Leask.  Joanna wanted but one thing… to be… Continue reading