Potential Stomach Virus Vaccine is Promising

**Admiral Piett** · February 16, 2012, 06:18 AM

An experimental vaccine has been shown in a small study to protect people from norovirus, infamous for sickening hundreds in outbreaks aboard cruise ships.

Noroviruses spread from person to person and through contaminated food or water, causing diarrhea, vomiting and stomach pain. The infection causes more than 20 million cases of acute astroenteritis annually in the United States, and there is no treatment.

Researchers tested a vaccine containing a weakened, noninfectious version of the virus in hopes that it would prompt a protective immune response in humans. Seventy-seven healthy men and women aged 18 to 50 participated. In two doses given three weeks apart, 38 subjects received the vaccine and 39 an inactive placebo. The results appeared in the Dec. 8 issue of The New England Journal of Medicine.

After the second dose, all volunteers drank a liquid containing norovirus. Infection and illness developed in 37 percent of those who received the vaccine, compared with 69 percent of those who took the placebo. Among those infected, the illness was less severe and of shorter duration in the vaccine group, and the vaccine had no serious side effects.

Still, a marketable vaccine is years away, according to Dr. Robert L. Atmar, the lead author of the study and professor of medicine at Baylor. “What this shows is a proof of principle that norovirus can be prevented through vaccination,” he said.

The study was paid for by grants from the N.I.H. and from LigoCyte Pharmaceuticals.

http://www.nytimes.com/2011/12/13/he...s-promise.html

FINALLY. I always thought that the stomach bug was the most neglected class of illness which is amongst the most prevalent of common diseases, rivaled only by the common cold and the flu. To be honest, I'd rather take either of the latter over the winter stomach bug. My emetophobic tendencies simply shrill everytime January rolls around. This year there's a highly publicized strain going around, infecting half the cast of American Idol. Norovirus is the most common cause of stomach illness in the world and its high time we finally started developing some vaccines to help against this garbage. I've been more seriously ill from this stuff than any flu. The fact that anywhere from 50 - 60% of acute gastroenteritis is caused by this should have led to vaccine studies a long time ago.

If I had it my way, I would deal with the problem ala zombie outbreak. Shoot all victims, barricade the windows, and eat from only from cans and sealed packages.

**Robertclive** · February 18, 2012, 02:45 PM

I haven't had that virus since 4th grade(knocks on wood), but I never want it again lo..

**Logios** · February 19, 2012, 07:12 PM

It could be to early to get your hopes up about this vaccine. The article describes a phase I clinical trial that gave a proof of concept but did not give an obvious lead to a phase II trial. IMO this trial is not useful since the placebo group did not receive the adjuvant monophosphoryl lipid A (MPL) in the placebo solution, just the sugars used to stabilize and flavor (it is formulated as a nasal spray).
Lots of changes are needed before a new phase I trial with a new, more effective formulation could be attempted.
The Virus-like particles (VLP) used in this trial are monovalent, protecting only against the GI types of norovirus while the GII types (particularily GII.4) are more commonly associated with current infections. The new vaccine formulation should either contain VLP's of both types expressed and self-assembled separately or VLP's combined from both types combined into single multivalent VLP's. The dream scenario could be if a highly conserved epitope was identified (an amino acid sequence found in all noroviruses), but with the high diversity of noroviruses this is not likely.
Even digging in the references to the references of the article could not precisely reveal to me the similarity of the VLP's to the virus itself in regards to size similarity as one article describes a factor 100 difference in this: http://jid.oxfordjournals.org/conten...t_2/S317.short while another (from 1992) describes them to be of similar size: http://jvi.asm.org/content/66/11/6527.abstract
I found an article not on the reference list of th OP article about research in multivalent NV VLP's, but those used here lacks some further development: http://www.sciencedirect.com/science...64410X06003975
The VLP's described in those articles were all expressed in insect cells made transgenic using a baculovirus as a vector for the norovirus capsid protein gene. (except for the last one where a mammalian cell-line was used) This is an expensive and slow expression platform, and one difficult to scale up to huge production tanks needed to provide so much product that it becomes even remotely affordable. Other vaccines consisting of VLP's (like Gardasil) are expressed in recombinant S.cerevisiae yeast (baking/brewing yeast), but are still quite expensive compared to more oldfashioned vaccines. Some articles exists that describe expression of the VLP's in trangenetic tobacco and potatoes, but if that succeeds it would be truly groundbreaking (have not read those yet, sorry).
What is your blood type, @Future Filmmaker. Maybe you are immune to the norovirus if you have type B or AB or if you are of A or O with a defective FUT2 gene, because in those cases the virus will not be able to attach itself, as the right proteins will not be present on the gut wall.
An article on this, that seems to be open-access (ref. 11 of the OP article): http://jid.oxfordjournals.org/content/185/9/1335.short
All in all it would take about 5 years (just my educated guess here) before a working vaccine is available and it will be quite expensive. It may not be affordable for those in the 3. world who actually die from stomach flu, and on our parts better hygiene in food handling and in general (wash those hands!) may be more effective. Avoid raw molluscs and raw (esp. frozen) raspberries (and some other foods that may have been contaminated with sevage)
BTW, I feel for those from the OP article who could not make the nasal spray devices work, and lol at the person being excluded from the placebo group after vomiting from overeating, just the thing to do while you are being paid to contract stomach flu.

**Admiral Piett** · February 21, 2012, 06:27 AM

Your links seem to be more about Norwalk virus rather than Norovirus. Much of it I don't really the technical language of it.

No one is actually immune to norovirus. Just certain genes and blood types have a higher resistance to it if I'm not mistaken. My type is A-.

Washing hands only goes so far when the virus itself is immune to a lot of sanitizers and it can take as little as 10 particles to cause infection. The fact that this particular virus affects an estimated 20 million Americans every year is just astounding. Sure, flu sucks, but for the most part the flu is a preferable calamity.

**Logios** · February 21, 2012, 03:25 PM

Originally Posted by Future Filmmaker

Your links seem to be more about Norwalk virus rather than Norovirus. Much of it I don't really the technical language of it.

No one is actually immune to norovirus. Just certain genes and blood types have a higher resistance to it if I'm not mistaken. My type is A-.

Washing hands only goes so far when the virus itself is immune to a lot of sanitizers and it can take as little as 10 particles to cause infection. The fact that this particular virus affects an estimated 20 million Americans every year is just astounding. Sure, flu sucks, but for the most part the flu is a preferable calamity.

The Norwalk virus is a particular strain of Norovirus named after the place of a major outbreak (Norwalk, Ohio. 1968). Other species of this genus exists and are named after the placed where outbreaks first occured. Following the discovery of other Norovirus strains than the Norwalk virus the entire genus of 40+ species categorized in 5 genogroups was named Norovirus (in 2002) while the specific GI.1 strain retained the Norwalk virus name. It was the GI.1 (Norwalk) that was used in the trial that the OP artcile is based on, both for the genetic sequence used to produce the virus-like particles and later to challenge the test persons. (I hope they pay them enough)
In Denmark (Europe) where I am from we had an outbreak of a strain very similar to the Norwalk virus which was named the "Roskilde"-disease after the town that was hit (it is on the Stainless Steel map BTW), but today this term is used in general in Denmark about any diarrhea condition regardless of the causative agent.
http://en.wikipedia.org/wiki/Norovirus
http://emedicine.medscape.com/article/224225-overview
Do you have full access to the articles? Here is the introduction to the one you posted in the OP:

Spoiler Alert, click show to read:

Noroviruses are a leading cause of epidemic acute gastroenteritis and are also an important cause of sporadic cases of acute gastroenteritis.1 Because human noroviruses have not been grown in cell culture and there are no convenient animal models in which to evaluate immunity and illness, much of our knowledge about these viruses comes from the study of outbreaks and experimental human infection. Norwalk virus (genotype GI.1), the prototype human norovirus, caused a school-based outbreak of epidemic gastroenteritis in 1968,2 and it is the most extensively studied human norovirus.3-5 Susceptibility to Norwalk virus infection is dependent on expression of a functional fucosyltransferase 2 (FUT2) gene; persons who have a nonfunctional FUT2 gene are genetically resistant to Norwalk virus infection.6,7 The FUT2 gene is involved in expression of the histo-blood group antigen H type 1 on the surface of epithelium. H type 1 and other histo-blood group antigens serve as receptors or attachment factors for human noroviruses and thus influence host susceptibility.1,8,9 Norwalk virus viruslike particles (VLPs) bind less to B histo-blood group antigens than to A or H histo-blood group antigens, and persons in whom the blood group B antigens are expressed are less likely to become ill if infected with Norwalk virus.10,11 Similarly, persons with serum antibodies that block the binding of Norwalk virus to H type 1 histo-blood group antigen are less likely to become ill if infected with Norwalk virus.12
Currently, there is no vaccine to prevent human norovirus infection, and there is no specific therapy available to treat it. Expression of the capsid proteins in eukaryotic cells leads to the spontaneous formation of VLPs,13 and these particles have been immunogenic in animal models, whether delivered parenterally, orally, or intranasally.14,15 A monovalent Norwalk virus VLP formulation delivered intranasally induced virus-specific serum antibodies in the majority of vaccine recipients.16 The purpose of the current study was to determine whether the vaccine provides protection against illness after a homologous norovirus challenge.

You can just ask if you have any questions to some of the tecnical terms or want a PDF of one of the articles.

About the 10 virus particles: I could not find anything about how many was needed to infect a person, but the detection limit of an ELISA test for the virus is in that range (on the wiki-page), but it is highly contagious, and one particle should in theory be enough.
True enough, no-one can be considered totally immune it seems, but the resistance seen in people with blood types AB and B and with defective FUT2 is pretty high though. I have added a result table from the last article in my first post. Unfortunately only 5 type B and 2 type AB subjects were included, which is maybe not enough for statistical significance. I am type 0+ myself and I don't know my FUT2 status. The "zombie outbreak" approach seems like a good idea.
The wiki-page also mentions ongoing phase II trials, but I could only find phase I trials for Norovirus (3 development phases exists in clinical trials of medicines):
http://clinicaltrials.gov/ct2/results?term=norovirus

**Admiral Piett** · February 23, 2012, 02:38 AM

Thanks for the explanations, man. Have some rep.

But surely it is progress no? Unless I read the numbers wrong, there was a difference of 37% developed symptoms with the trial and 69% developed them with placebo.

**Logios** · February 23, 2012, 11:15 AM

Originally Posted by Future Filmmaker

Thanks for the explanations, man. Have some rep.

But surely it is progress no? Unless I read the numbers wrong, there was a difference of 37% developed symptoms with the trial and 69% developed them with placebo.

It is a proof of concept in human test subjects, yes, but considering that all the tests in animals and the first tests in humans has to be redone with a new vaccine targeting all noroviruses and not just the GI.1, it must be considered a very small step on a very long road. The overall efficacy must be improved as well since 100% rather than 63% is generally expected for a vaccine, especially considering that it might cost $100+ per shot (and you will need two with some time in between).
The percentages might have been different if the placebo compound had contained the adjuvant ("helper"-compound) as this on its own activates the immune system.

**Killerbee** · February 23, 2012, 10:13 AM

I had it once when I was 12. It truly sucks. I threw up the night I got infected and the following morning and passed out . I just stayed in bed for 2 days, because I got very sick every time I stood up. It really does give you emetophobic tendencies.

**MathiasOfAthens** · February 23, 2012, 10:27 AM

Dude who the

cares... havnt you heard? We are all going to die. Scientists created a stronger bird flu that they say will kill millions... they claim its safe under lock and key but I bet you anything it will get out and then its over.

**Killerbee** · February 23, 2012, 01:55 PM

Originally Posted by MathiasOfAthens

Dude who the

cares... havnt you heard? We are all going to die. Scientists created a stronger bird flu that they say will kill millions... they claim its safe under lock and key but I bet you anything it will get out and then its over.

From what I heard, they merely performed a few manipulations on the bird's virus to see how long it would take for the virus to also be dangerous for human beings. They didn't actually create a virus and then lock it like some sort of super weapon. You saw too much movies man.

**MathiasOfAthens** · February 23, 2012, 02:00 PM

How do you know?

**Logios** · February 23, 2012, 03:22 PM

Originally Posted by MathiasOfAthens

How do you know?

The immune system is extremely diverse in humans, only identical twins has the same tissue type. No matter how a super-virus is designed there will always be some who are immune, either by not expressing anything the virus can attatch to (like discussed earlier) or by chance having immune cells with high affinity towards epitopes on the causative agent.
But I assume you are being ironic

There is something on it here, but it is pretty heavy reading for a wiki-page:
http://en.wikipedia.org/wiki/Major_h...bility_complex