Wednesday, 16 November 2016

#ResearchSpeak: MS prevention can we make it a reality?

We will need Big Pharma to help us develop and commercialise an anti-EBV vaccine to prevent MS. #ResearchSpeak #MSBlog

I spent the best part of my 30th wedding anniversary writing a preventative neurology grant targeting EBV and infectious mononucleosis as therapeutic target to prevent MS. This is a strategic development grant for our medical school and something that brings together 15+ years of thinking and work. I am excited. 


The question is does an anti-EBV vaccine have to cause sterilising immunity, i.e. prevent infection with EBV completely, or can it just prevent IM. As IM is the main risk factor for MS, simply preventing it may be sufficient to protect recipients from developing MS. If this is the case then we have thrown the baby out with the bathwater. The GSK vaccine below did just that; it prevented IM, but not wild-type EBV infection. As it did not stop wild-type EBV infection GSK stopped developing the vaccine and sold it to Medimmune. The last we heard is that Medimmune have mothballed the programme and the vaccine is not going anywhere soon. More worrying is the business case for an EBV vaccine; believe it, or not, IM & MS prevention are not sufficiently big enough to support the market for an EBV vaccine. The business case will need to be based on oncoprevention, i.e. preventing lymphomas. The scary thing is that Big Pharma need the vaccine to sell upwards of ~$2 billion per year to justify the investment in developing and producing such a vaccine. Vaccine development is a risky, and very expensive, business. As it has been shown with Ebola, and now Zika, infection the commercial development and large scale production of vaccines can only be done by Pharma. Governments simply don't have the resources, know-how and appetite for risk to take vaccine development on. Interestingly, they did in the past. What has changed? The regulatory environment and rules governing safety. Commercial vaccine development arguably one of the greatest innovations of all time is beyond is now in the hands of Pharma. Is this a good idea? 

However, we have decided that we are not going to get despondent and worry about the business case. We believe that there is an unmet need for an effective anti-EBV vaccine and that human perseverance and determination will come through at the end of the day. We have a dream; 'a world free of MS'


Sokal et al. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virusvaccine in healthy young adults. J Infect Dis. 2007 Dec 15;196(12):1749-53.

BACKGROUND: To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus.


METHODS: A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen.

RESULTS: The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine.

CONCLUSION: These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00430534.

11 comments:

  1. Of four siblings three of us have had the EBV virus (glandular fever) I have MS, my sister has sarcoidosis and my brother worried me recently experiencing unexplained blurred vision. I am not unsurprisingly strongly in favour of a vaccine. To what extent is the link being made across other conditions such as Sarcoid? The MS community may not be deemed big enough, but if a larger proportion of the human population could be included, would this be more likely to engender investment in a vaccine?

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  2. An MS Prevention Task-force.

    Task-force: a group or committee, as of experts, formed to examine or solve a specific problem.

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    1. Re: "An MS Prevention Task-force."

      Yes, good idea. I sit on three such groups, one run by the UK MS Society, one funded by the NMSS and one Prof. Nick Wald has recently set-up around EBV vaccination as a strategy to prevent MS.

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  3. How about a low dose course of something like cladribine for children of people with autoimmune disease? I have MS, son has mild scleroderma, alkylating spondylosis, daughter has schitzoaffective disorder. Overactive and inappropriate immune system activity for all of these diseases are implicated.

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    1. Unfortunately, this would be too risky! Low dose cladribine probably won't work. The current dose we using in MS is far too low, if only we could use a higher dose it may be as good as alemtuzumab. We had to choose a low dose to prevent prolonged lymphopaenia and the consequences of long-term lymphopaenia.

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    2. Re "if only we could use a higher dose it may be as good as alemtuzumab".
      Have Barts noticed if patients are overweight or obese they do less well on cladribine, than those that are not? As it is a standard dose.

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  4. How do the medical-scientific community adhere to MS prevention through EBV prevention / research?

    Many neurologists are still reticent about the possible causality between EBV infection and MS, are even doubtful as to the relationship of low vitamin D dosage and disease ...

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    1. Re: "Many neurologists are still reticent about the possible causality between EBV infection and MS"

      Slow adopters. Have you have heard about Schopenhauer's dictum?

      All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.

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  5. "Governments simply don't have the resources, know-how and appetite for risk to take vaccine development on. Interestingly, they did in the past. What has changed?"

    Is it due to neoliberalism and the fact everything but everything is related to profits?

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    1. Re: "What has changed?"

      The regulatory environment; the costs have soared. Sanofi has had to spend close to $1B just to build the production facilities for their pneumococcal vaccine. The new you need multiple large scale trials, the cost of insurance, etc. It unbelievable how much tick the boxes for the regulators costs. Gone are the days of making vaccines in academic labs.

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  6. I have read a lot about the EBV. It is known as the mystery illness which causes other mystery illnesses. After the infectious active phase of the virus it lies under the surface attacking something else- your thyroid, your gut , your joints or your nervous system. I told my neuro that I was following an anti-ebv diet and he laughed at me. I would love my children to have an anti-ebv vaccine. Also I reckon if we could completely eradicate the EBV virus from our bodies then maybe MS progression would be halted !

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