Saturday, 23 January 2016

ResearchSpeak & CrowdSpeak: EBV vaccination

Why EBV vaccination may not be the best solution to prevent MS. #CrowdSpeak #MSBlog #MSResearch

"Somebody asked me: 'if you think MS is caused by EBV why don't you simply vaccinate the population against EBV and see what happens?'. This is easier said than done. In addition, population vaccination is a 'hot potatoe'; you just have to read the political fallout of the HPV vaccine for cancer of the cervix prevention to gain some insights into how political the topic of 'population vaccination' can be."



"However, I agree with you the real test of the EBV-MS hypothesis is vaccination. However, the read-out on MS incidence will take 20-30 years. The latency period from environmental exposure to onset of MS is predicted to be in the order of 20-30 years on average. We know this from the Iranian MS epidemic. We think the epidemic of MS in Iran was triggered, and is being sustained, by vitamin D deficiency in women due to mandatory covering-up after the Iranian revolution in 1978. Prior to the revolution vD levels in Iranian women were similar to men. After the revolution Iranian women have been shown to have much lower plasma vD levels than men. The MS epidemic in Iran was noted to start about 20 years later as is mainly in female population. The female to male ratio of incident case of MS in Iran is 5 to 1; the highest ratio in the world and is increasing."

"Before testing a EBV vaccine we need one that works. The last EBV vaccine to be tested was not effective in preventing wild-type EBV infection and as a result was not licensed. The good news is there are renewed efforts at the NIH  to develop a new EBV vaccine despite many challenges. The paper below summarises these challenges. As you can see the main driver for the EBV vaccination programme is onco-prevention and not the prevention of autoimmune diseases. That doesn't really matter as an effective anti-EBV vaccine that prevents EBV-associated tumours should also prevent autoimmunity, in our case MS. In addition it would also prevent IM (infectious mononucleosis) or glandular fever, the main risk factor of EBV exposure when it comes to MS risk."



"Are there any theoretical dangers of EBV vaccination? Yes, I have rehearsed the arguments against EBV vaccination before on the blog. EBV is part of our meta-genome and is one of the most co-evolved viruses to infect humans (meta-genome simply refers to the contribution the microbial genome makes to human biology). I therefore suspect that at a population level EBV must be doing us some good and if we suddenly cull EBV from our metagenome there may be consequences. I have previously hypothesised that as EBV infected B cells have a propensity to survive longer than non-EBV infected B cells, EBV may be responsible for augmenting B cell memory and hence longterm antibody responses. This may mean that if we prevent EBV infection we may reduce our B cell memory; in other words we would be causing a sort of Alzheimer's of B-cells or forgetful B-cells. The so called forgetful B cell hypothesis. We won't really be able to test this until several decades after a mass population-based EBV vaccination programme has started."

"The theoretical and logistical hurdles in relation to EBV vaccination is why finding successful drug treatments that target EBV is so important. May be we won't need vaccination if we can take a simple over the counter safe anti-viral to treat IM and possibly MS. This is why our Charcot project is so important. If you haven't donated money yet please consider doing so now. We have almost reached our target for phase 1 of next antiviral agent we want to test in MS."
Click here to find out more!

Cohen et al. The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine. 2013 Apr 18;31 Suppl 2:B194-6.

Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with several malignancies including nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and lymphoma after organ or stem cell transplant. A candidate vaccine containing soluble EBV glycoprotein gp350 protected cottontop tamarins from EBV lymphoma after challenge with EBV. In the only phase 2 trial of an EBV vaccine in humans, soluble gp350 in alum and monophosphoryl lipid A adjuvant reduced the rate of infectious mononucleosis in EBV seronegative adults, but did not affect the rate of EBV infection. A peptide vaccine corresponding to EBV latency proteins has been tested in a small number of adults to prevent infectious mononucleosis. Some of the barriers to development of an EBV vaccine include (a) whether viral proteins in addition to gp350 would be more effective for preventing mononucleosis or EBV malignancies, (b) the difficulty of performing clinical trials to prevent EBV associated malignancies in the absence of good surrogate markers for tumor development, and the long period of time between primary EBV infection and development of many EBV tumors, (c) the lack of knowledge of immune correlates for protection against EBV infection and disease, (d) the limitations in animal models to study protection against EBV infection and disease, and (e) the need for additional information on the economic and societal burden of infectious mononucleosis to assess the cost-benefit of a prophylactic vaccine.

15 comments:

  1. EBV as part of the metagenome brings to mind bad software - it may do a job, but not necessarily very efficiently, and it causes a lot of bugs and blips along the way. I think I would be all to ready to obliterate my EBV - if I could - and see what happens, even though, if I take the computer analogy too far, I have learned painful lessons in the past from experimental deletion of things on my laptop I didn't fully understand! But ~10% of the population don't have EBV, so it surely can't be that crucial? Anyway, I hope that an antiviral can treat or at least control MS.

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    1. The analogy that you did Sterntaucher was exactly what I was already thinking about it. EBV infects 90% of the world population, 10% who knows why were not infected, and of these 90% infected it causes some disorder, as well as EBV is associated with certain forms of cancer, such as Hodgkin's Lymphoma, Burkitt's Lymphoma , Nasopharyngeal Carcinoma and conditions linked to HIV (Hairy Leukoplakia and Lymphomas of the central nervous system). And as I posted in a previous review, EBV appears to be linked to other autoimmune conditions, are looking for Lupus mostly.
      There is also evidence that EBV infection is associated with dermatomyositis, lupus, Sjögren's syndrome rheumatoid arthritis (it looks like a lesser extent with the RA). So if EBV is part of the metagenome, and comparing with a software, it is very buggy so yes, more buggy than having your possible action "beneficial" is intended or actually utilized...
      Oncologist when they look at EBV and its causality with Hodkings Lymphoma think they opine for their extermination even ...

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    2. Yes - it seems a wonder, given all the system failures that EBV is associated with, that there has not been an awful lot of research into antivirals specific to EBV already, long ago!

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  2. Prof G - Given your Iran example, shouldn't we be investigate how vit d affects EBV? Perhaps it helps keep it under control?

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    1. Would I be correct in saying mono is an upper respiratory infection due to the throat symptoms?

      "Studies have shown that there is a link between vitamin D levels and the risk of getting a respiratory infection. People who have low vitamin D levels tend to have a higher chance of developing a respiratory infection."
      http://www.vitamindcouncil.org/health-conditions/respiratory-infections/

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    2. That seems a good question - I'd be interested in the answer to that too,

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    3. On this topic, I thought this to be interesting (in German):
      http://aktuell.ruhr-uni-bochum.de/pm2012/pm00322.html.de

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    4. As Mono often affects the spleen and liver and the virus is throughout the body then no it is nothing like an upper respiratory infection.

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    5. The same page on the vitamin D Council site goes on to say some interesting key points and I wonder if young adults have a good vitamin D level could this reduce the risk of them getting mono?

      Key points from the research
      •People who get respiratory infections are more likely to have low levels of vitamin D.

      •Vitamin D can help reduce inflammation caused by the respiratory infections and increase the number of proteins that fight against viruses.

      •Respiratory infections tend to increase during the winter, which is when vitamin D levels are known to decrease in the population.

      •Some experiments have shown that taking vitamin D supplements can help to prevent respiratory infections, but results are mixed.

      •Some research has shown that people with high levels of vitamin D who get respiratory infections have a shorter illness duration or less severe symptoms.

      •Some researchers recommend getting more vitamin D to protect against respiratory infections. Still, more experiments are needed for scientists and doctors to clearly understand whether or not taking a vitamin D supplement can prevent respiratory infections.

      http://www.vitamindcouncil.org/health-conditions/respiratory-infections

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    6. Important to note Mono can be caught through coughs and sneezes too, not just kissing and sharing food.

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    7. Some URI's (upper respiratory infections) can be very nasty. Tonsillitis can have complications if left untreated, rare complications such as scarlet fever and rheumatic fever which can lead to painful inflammation throughout the body and other complications.
      My grandmother had rheumatic fever.

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  3. When people are diagnosed as having glandular fever it would be interesting to know their vitamin D level. Is this something that is already now tested ?
    Of course those who have glandular fever need lots of rest and nutritious food to help them recover.

    If people are given high dose vitamin D if they are diagnosed with glandular fever does that help the recovery? If they have low levels of vitamin D.

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  4. Congratulations Prof G and all we reached the target for crowdfunding!! Prof G you did a great job promoting it all.

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    1. Thanks I was going to put a few bob in but too late.

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  5. Congratulations on meeting the target. Would anti-virals targeting EBV have any effect on MS activity? If not, why not?

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