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This Vaccine Could Be a Game-Changer for People with Celiac Disease

Can a vaccine for celiac diseasse change the way the disease is treated?


Can a vaccine work against celiac disease? Photo: MilitaryHealth

Celiac.com 05/29/2017 - Currently, a gluten-free diet is the only way to manage celiac disease. Can a celiac vaccine change that? One company thinks so. ImmusanT corporation has developed a therapeutic vaccine, Nexvax2, that is specifically designed to treat celiac disease. The vaccine is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is designed to neutralize gluten-specific CD4-positive T cells to further antigenic stimulation.

As part of their efforts to evaluate the vaccine, a team of researchers recently set out to investigate the efficacy of epitope-specific immunotherapy targeting CD4-positive T cells in celiac disease. Specifically, they assessed the safety and pharmacodynamics of the Nexvax2 vaccine in patients with celiac disease on a gluten-free diet.

An article detailing the findings of their most recent effort, titled Epitope-specific immunotherapy targeting CD4-positive T cells in celiac disease: two randomized, double-blind, placebo-controlled phase 1 studies, appeared in the Lancet.

The research team included Gautam Goel, PhD, Tim King, MBBChir, A James Daveson, MBBS, Jane M Andrews, MBBS, Janakan Krishnarajah, MBBS, Richard Krause, MD, Gregor J E Brown, MBBS, Ronald Fogel, MDCM, Charles F Barish, MD, Roger Epstein, MD, Timothy P Kinney, MD, Philip B Miner Jr, MD, Jason A Tye-Din, MBBS, Adam Girardin, BS, Juha Taavela, MD, Alina Popp, MD, John Sidney, BS, Prof Markku Mäki, MD, Kaela E Goldstein, BS, Patrick H Griffin, MD, Suyue Wang, PhD, John L Dzuris, PhD, Leslie J Williams, MBA, Prof Alessandro Sette, DrBiolSc, Prof Ramnik J Xavier, MD, Prof Ludvig M Sollid, MD, Prof Bana Jabri, MD, and Dr Robert P Anderson, MBChB.

To assess the safety and pharmacodynamics of the vaccine in patients with celiac disease on a gluten-free diet, ImmusanT recently conducted two randomized, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18–70 years who had celiac disease and were following a gluten-free diet.

The goal of the study was to document the number and percentage of adverse events in the treatment period in an intention-to-treat analysis.

The study enrolled a total of 108 participants from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3, 2012, to Sept 10, 2013, in the 16-dose study.

Overall, 62 (57%) of 108 participants were randomly assigned after oral gluten challenge and 20 (71%) of 28 participants were randomly assigned after endoscopy.

None of the study participants, investigators, or staff knew which patients received a given treatment; these details were known only by the study’s lead pharmacist.

In the three-dose study, participants received either Nexvax2 60 μg, 90 μg, or 150 μg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or a placebo.

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In the 16-dose study, participants received Nexvax2 150 μg or 300 μg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or a placebo. In both studies, about 5% of the participants reported were vomiting, nausea, and headache.

Among participants given the MTD, four of eight subjects in the third cohort experienced adverse gastrointestinal treatment-emergent events; zero of three participants had adverse events in the biopsy cohort in the three-dose study, while five events occurred in five (63%) of eight participants in the first cohort, and three events in two (29%) of seven participants in the biopsy cohort of the 16-dose study.

Those who received the vaccine at the MTD on either schedule showed no significant difference between average villous height to crypt depth ratio in distal duodenal biopsies, as compared with those who received placebo.

In the 4-week post-treatment period, ascending dose cohorts underwent a further double-blind crossover, placebo-controlled oral gluten challenge, which had a fixed sequence. Meanwhile, biopsy cohorts received a gastroscopy with duodenal biopsies and quantitative histology within 2 weeks without oral gluten challenge. Of the participants who completed the post-treatment oral gluten challenge per protocol, interferon γ release assay to Nexvax2 peptides was negative in two (22%) of nine placebo-treated participants in the three-dose study.

Compared with two (33%) of six who received Nexvax2 60 μg, five (63%) of eight who received Nexvax2 90 μg, and six (100%) of six who received Nexvax2 150 μg (p=0·007); in the 16-dose study, none (0%) of five placebo-treated participants had a negative assay versus six (75%) of eight who received Nexvax2 150 μg (p=0·021).

The MTD of Nexvax2 was 150 μg for twice weekly intradermal administration over 8 weeks, which modified immune responsiveness to Nexvax2 peptides with no adverse impact on duodenal histology.

Patients who received the intradermal administration of the vaccine reported gastrointestinal symptoms were not subtantially different to those seen with oral gluten challenge.

While the commercial release of a viable vaccine is likely still some time away, early-phase trials have shown promise. Based on these results, ImmusanT will continue clinical development of this potentially therapeutic vaccine for celiac disease.

Both trials were completed and closed before data analysis. Trials were registered with the Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729.

Source:

Affiliations:
The researchers are variously affiliated with the Division of Gastroenterology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA, the Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA; the Department of Gastroenterology, Auckland City Hospital, Auckland, New Zealand; the School of Medicine, University of Queensland, Brisbane, QLD, Australia; the Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia; the Linear Clinical Research, Nedlands, WA, Australia; the Department of Gastroenterology, Alfred Hospital, Prahran, VIC, Australia; the Clinical Research Institute of Michigan, Chesterfield, MI, USA; the University of North Carolina School of Medicine, Chapel Hill, NC, USA; Wake Gastroenterology and Wake Research Associates, Raleigh, NC, USA; Atlantic Digestive Specialists, Portsmouth, NH, USA; Ridgeview Medical Center, Waconia, MN, USA; Oklahoma Foundation for Digestive Research, Oklahoma City, OK, USA; ClinSearch, Chattanooga, TN, USA; the Immunology Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; the Murdoch Children's Research Institute and Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia; the Immunology Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; the Tampere Center for Child Health Research and Department of Pediatrics, University of Tampere Faculty of Medicine and Life Sciences and Tampere University Hospital, Tampere, Finland; the Tampere Center for Child Health Research and Department of Pediatrics, University of Tampere Faculty of Medicine and Life Sciences and Tampere University Hospital, Tampere, Finland; the Alfred Rusescu Institute for Mother and Child Care and Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; the Tampere Center for Child Health Research and Department of Pediatrics, University of Tampere Faculty of Medicine and Life Sciences and Tampere University Hospital, Tampere, Finland; the Centre for Immune Regulation, KG Jebsen celiac Disease Research Centre, and Department of Immunology, University of Oslo, Oslo, Norway; the Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Pediatrics, Department of Medicine, University of Chicago, Chicago, IL, USA; and ImmusanT in Cambridge, MA, USA.

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15 Responses:

 
Tamra Little
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said this on
30 May 2017 6:55:33 PM PDT
When is it likely to be available in the US?? So hopeful!!

 
Janet
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said this on
06 Jun 2017 3:26:44 AM PDT
I am 63 and I have celiac. I am gluten free and would love to take the vaccine but will not get my hopes up. I probably will be too old or not present at the time!

 
Marie
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said this on
06 Jun 2017 9:05:33 AM PDT
I had read about a problem with this vaccine and it was only DQ2 who could take it. I do not think a vaccine is the answer, genetic manipulation before birth is.

 
Kristine Slager
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said this on
05 Jun 2017 10:22:25 AM PDT
Knowing the inefficacy and and numerous, horrific results of most vaccines, I can't even begin to imagine the nightmares this may cause. And all so you can eat a specific food?!? Following a gluten-free diet is 100% safe with 100% efficacy. Experiment on our family with a vaccine so we can eat a damn doughnut?? NO THANK YOU.

 
admin
( Author)
said this on
08 Jun 2017 8:31:05 AM PDT
What horrific results are you talking about...no more small pox, or that you are not worried about polio?

 
Jeff Adams
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said this on
14 Jun 2017 4:05:05 PM PDT
Most vaccines are, in fact, highly effective. In fact, I can't name a major vaccine that does not work as designed. Can you? So, far from causing "nightmare" scenarios, most vaccines actually reduce death and debilitation from preventable diseases. Also, I'm not sure the folks who are developing this vaccine are planning to "experiment on your family." I'm pretty sure they plan on testing it thoroughly in trials and then on human volunteers to make sure it is safe and effective before they make it commercially available. That is standard practice with all vaccines. Lastly, vaccines save lives. Vaccine hysteria promotes unnecessary suffering and, potentially, preventable deaths.

 
Will
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said this on
05 Jun 2017 3:05:24 PM PDT
Another unreadable article. Tell us in plain English what the results were.

 
admin
( Author)
said this on
08 Jun 2017 8:30:15 AM PDT
Some of the science just can't be easily simplified.

 
Jeff Adams
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said this on
14 Jun 2017 4:14:11 PM PDT
In an effort to assess how well the vaccine is tolerated in humans, it was tested on several groups at several doses. It seemed to work okay. Nothing horrible happened. Aside from a few mild side effects, things went well. Stay tuned for the results of the forthcoming trials.

 
margie
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said this on
05 Jun 2017 9:21:15 PM PDT
You have got to be kidding. With the toxic elements in vaccines and no long-term studies to judge the possible effects of vaccine ingredients, celiac sufferers have enough problems without adding vaccine complications to the list.

 
Jeff Adams
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated ( Author)
said this on
14 Jun 2017 4:09:48 PM PDT
Toxic elements in vaccines? I'm not sure what you mean. Originally, many early vaccines contained small amounts of lead, then later mercury, then later aluminum. Again, we are talking micro-doses as a vaccine delivery vehicle. Literally hundreds of millions of people have received vaccines, and tolerated them perfectly fine. Lives have been saved. Unnecessary suffering, maiming and death have been prevented.

 
LMS
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said this on
06 Jun 2017 5:27:19 AM PDT
No way would I get vaccinated for something controllable through diet! The ingredients in vaccines are questionable at best.

 
Marie LaRock
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said this on
06 Jun 2017 7:04:41 AM PDT
This would sure make my life a lot less complicated! Hope it will be available soon!

 
Hailey
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said this on
15 Jun 2017 7:42:55 PM PDT
I'm really hoping this vaccine will pass the next trials! I don't understand all the negativity with this. If you don't want to take it, fine. But don't ruin it for others. I am so excited about this.

 
Josh
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said this on
24 Aug 2017 1:39:40 PM PDT
Any updates on an expected release date? It would be such a burden off my shoulders to be able to eat out at a restaurant and not worry about cross contamination when I travel.




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