The cure for the flu is coming in 2012

[Brainonska511]

It's a vaccine that's aimed at raising a T cell response specifically against some viral proteins.

I thought I read about this somewhere else too - it might have been a paper in a similar vein of thought. If I remember correctly, the goal was to get the immune system to react against parts of the virus coat proteins that are highly conserved (rarely mutate), thus providing protection against a range of influenza types. Of course, computational design sounds great in theory, but it is difficult to work out in practice, thus leaving a lot to large scale screens...

 

[Gibsons]

I thought I read about this somewhere else too - it might have been a paper in a similar vein of thought. If I remember correctly, the goal was to get the immune system to react against parts of the virus coat proteins that are highly conserved (rarely mutate), thus providing protection against a range of influenza types. Of course, computational design sounds great in theory, but it is difficult to work out in practice, thus leaving a lot to large scale screens...

That's a different thing...

Conventional, current vaccines against flu work by raising an antibody response against the viral protein HA, which is found on the surface of the virus. HA is shaped like... well, like a penis. Circumcised. Most or all of the antibodies raised by vaccines (and probably by infections as well) bind to the head portion of HA, the outermost part, furthest from the viral surface. This part of the protein varies a great deal between strains, and from year to year, hence the need for a new vaccine every year.

There have been attempts to get antibodies that bind to the 'shaft' portion of HA. This part shows a lot less variation, so in theory antibodies against it might be effective for long periods. Then again, we might just be applying selective pressure to a different place, with similar results.

 

[Mr. Pedantic]

I know what a paper is. Just i dont know what they mean by paper in this text.

An article, written directly by the scientists performing the research and for other scientists in the field, submitted, accepted, and published by a reasonably well-known peer-reviewed journal.

http://cid.oxfordjournals.org/content/52/1/1.full

Thank you.


That is pretty cool. I'm assuming that the nucleoprotein and matrix protein they immunized against are normally expressed on the external membrane of infected somatic cells, given the CD8+ rise. What would be really cool would be to see that given this is how T-cell populations respond ex vivo to the different administrations of the vaccine, how they respond in vivo and whether this has any influence on the incidence of influenza infection.


Of course, however, even though NP is highly conserved currently, given the vaccine and the new selective pressure of immunized humans, I wouldn't be surprised to see greater variance start to creep into NP as well.

 

[Gibsons]

That is pretty cool. I'm assuming that the nucleoprotein and matrix protein they immunized against are normally expressed on the external membrane of infected somatic cells, given the CD8+ rise.

Sort of. Not so much on the membrane, but peptides derived from it are found within or on a host surface molecule that's on the cell membrane. T cells kind of look initially for the surface molecule. If the surface molecule contains a foreign peptide, they can (hopefully) kill the cell. If it has self peptides they leave it alone (assuming there's no autoimmune process).

Of course, however, even though NP is highly conserved currently, given the vaccine and the new selective pressure of immunized humans, I wouldn't be surprised to see greater variance start to creep into NP as well.

I agree, this could be interesting. There's a little bit of variance in NP right now. It might be on a tighter evolutionary/functional leash than HA, but who knows.

 

[MotionMan]

I know what a paper is. Just i dont know what they mean by paper in this text.

In this context, a "published paper" is an article that is published in a credible, relevant, science publication.

MotionMan

 

[Mr. Pedantic]

I agree, this could be interesting. There's a little bit of variance in NP right now. It might be on a tighter evolutionary/functional leash than HA, but who knows.

I would assume that the reason they're more highly conserved because they're more important to the viral cycle, but on the plus side, this would at least give evolutionary biologists more proof of macro-evolution.

Sort of. Not so much on the membrane, but peptides derived from it are found within or on a host surface molecule that's on the cell membrane. T cells kind of look initially for the surface molecule. If the surface molecule contains a foreign peptide, they can (hopefully) kill the cell. If it has self peptides they leave it alone (assuming there's no autoimmune process).

So they get presented on MHC molecules? That makes sense. The immune system never 'made sense' to me, so I'm not so good on immune function, but...


From what I remember, normally viral particles would get caught by antigen-presenting cells, which then find out and signal to memory B cells in lymph nodes using their MHC proteins, which then differentiate into helper and plasma B cells, which upregulate antibody production and T cell differentiation...? Whereas the mechanism this paper relies on the MHCs on normal cells? How do the cells get viral proteins from inside the cell to be ultimately presented on MHCs outside the cells?

 

[BoomerD]

So how come the drug manufacturers wait until the world is supposed to end to find a cure for the flu?
Is that so they don't have to deal with unhappy stockholders when it doesn't really work?

 

[Alone]

I'm not one of those paranoid nuts or anything, but my body seems to do a relatively good job at ridding itself of illnesses shortly after they present themselves. I don't really see a purpose in fucking around with our immune systems just to save ourselves a couple weeks of discomfort.

 

[Red Squirrel]

People talk about the flu like it was some super bad disease like cancer. The flu is actually less bad than a cold.

Flu: lasts 24 hours with a few days of recovery. A bit of puking here and there, fever, lot of sleeping, next day you're a new person.

Cold: can last months. sore throat, coughing, runny and/or stuffy nose, fevers... colds are much worse. They just drag on and on forever and the symptoms are so aggravating.


So if this is a vaccine, then what is the flu shot? I figured it basically was a vaccine as well.

 

[BoomerD]

People talk about the flu like it was some super bad disease like cancer. The flu is actually less bad than a cold.

Flu: lasts 24 hours with a few days of recovery. A bit of puking here and there, fever, lot of sleeping, next day you're a new person.

Cold: can last months. sore throat, coughing, runny and/or stuffy nose, fevers... colds are much worse. They just drag on and on forever and the symptoms are so aggravating.


So if this is a vaccine, then what is the flu shot? I figured it basically was a vaccine as well.

No, influenza can kill millions of people.

http://virus.stanford.edu/uda/

http://en.wikipedia.org/wiki/Influenza_pandemic

While MOST influenza outbreaks are fairly mild, people still die every year from it.

 

[Mr. Pedantic]

I'm not one of those paranoid nuts or anything, but my body seems to do a relatively good job at ridding itself of illnesses shortly after they present themselves. I don't really see a purpose in fucking around with our immune systems just to save ourselves a couple weeks of discomfort.

Because the flu can be quite serious, and because not everyone has the luxury of being healthy with a normal immune system. Also, I don't see how getting a vaccine is "fucking around with our immune systems".

People talk about the flu like it was some super bad disease like cancer. The flu is actually less bad than a cold.


Flu: lasts 24 hours with a few days of recovery. A bit of puking here and there, fever, lot of sleeping, next day you're a new person.


Cold: can last months. sore throat, coughing, runny and/or stuffy nose, fevers... colds are much worse. They just drag on and on forever and the symptoms are so aggravating.

The flu is much worse. True, if you get the flu, then (if you are going to get better) the disease peaks around 24-48 hours in, whereas colds generally last closer to a week. However, there is a higher mortality rate associated with influenza and its symptoms are worse - the FDA thinks so too. Also, especially in elderly patients influenza can cause pneumonia, by itself or secondarily through bacterial infection, and this may be deadly as well.

So if this is a vaccine, then what is the flu shot? I figured it basically was a vaccine as well.

Both are vaccines. However, the way current influenza vaccines are made, researchers have to guess which strain is going to predominate the coming winter, because the proteins the vaccine 'targets' mutate so often. This new vaccine is trying to target different proteins that don't mutate so much, which means that a vaccine will be much longer-lasting before it's deprecated and will be effective the world over.

 

[MustangSVT]

ah.. so this is how the world ends in 2012.

 

[Wanescotting]

I'm not one of those paranoid nuts or anything, but my body seems to do a relatively good job at ridding itself of illnesses shortly after they present themselves. I don't really see a purpose in fucking around with our immune systems just to save ourselves a couple weeks of discomfort.

This...getting sick is part of life. If you die of said illness, it was your time to go, simple as that!

 

[eits]

According to http://www.telegraph.co.uk/health/healthnews/8307569/Universal-flu-vaccine-breakthrough.html there will be a cure for the flu. It attacks proteins in the flu and breaks them down. So basically no more flu's. No swine flu's no bird flu no nothing. The flu is very deadly so this cure will be huge for the elderly and children. Deadly flu's have been acouring more often example swine flu and bird flu. This eases my mind greatly. Im afraid something bad is going to happen in the near future to wipe out humanity weither its are own doing or biological or even extraterrestrial. At least this eases my mind a bit. These new flus coming out are very deadly and now we have a way to fight it.

I just wanna say 3 cheers to the ones that are coming out with this vaccine. You did a great job.

old news. and it still needs to be tested to be sure it's safe and effective long-term. but, yeah, i heard about this about 2 years ago.

 

[eits]

vaccine cure same thing in my book. Both make it sure you cant get sick.

not all vaccines make it so you can't get sick.

cures don't make it so you can't get sick.

 

[eits]

Is there a paper published on this yet? Seems pretty implausible TBH.

this.

 

[eits]

Im not sure what you mean by paper but its been on the news alot. Not that the news over exacturates things at all do they. I thought people would be saying old news by now on this thread im suprized no one has said it yet

sorry, came late to the party.

 

[eits]

Ignore the OP, it's basically wrong. This isn't a drug that 'breaks down proteins.'

It's a vaccine that's aimed at raising a T cell response specifically against some viral proteins.



It's a vaccine. It works more through T cells than antibodies though, that's the big deal. It doesn't "break down viral proteins." It causes T cells to specifically recognized infected cells and kill them. This is the best known defense against any virus.



http://cid.oxfordjournals.org/content/52/1/1.full

this.

this.

thanks.

yeah, basically, the hurdle they've been trying to jump, iirc, is to safely be able to boost t-cells to find the protein common to all flu virus strains... that way, even when they evolve, the vaccine will still be effective against it.

correct me if i'm wrong, gibsons.

[edit] i read the rest of the thread.

 

[eits]

So if this is a vaccine, then what is the flu shot? I figured it basically was a vaccine as well.

here's a very hyperbolic example, but imagine that you need to get from point a to point b... one year, point a to point b is straight ahead of you, so you buy a car that can only go straight... the next year, point a to point b is to the side of you, so you buy a car that can only go sideways. what if someone invented a car that could go straight, sideways, backwards, etc? then, you won't have to worry about ever figuring out which specific car to buy each year.

 

[Alone]

The edit button... it serves a purpose.

 

[Gibsons]

I would assume that the reason they're more highly conserved because they're more important to the viral cycle, but on the plus side, this would at least give evolutionary biologists more proof of macro-evolution.

There's already a demonstration of this with HIV. Most HIV proteins seem to have a bit of room to mutate and thus no longer get presented on MHC, ie there are 'escape mutants.' But there's one particular part of one particular protein that isn't so tolerant of mutations. People whose MHC can present that peptide mount a much more effective response against the infection.

So they get presented on MHC molecules? That makes sense.

Correct.

From what I remember, normally viral particles would get caught by antigen-presenting cells, which then find out and signal to memory B cells in lymph nodes using their MHC proteins, which then differentiate into helper and plasma B cells, which upregulate antibody production and T cell differentiation...? Whereas the mechanism this paper relies on the MHCs on normal cells? How do the cells get viral proteins from inside the cell to be ultimately presented on MHCs outside the cells?

Yes, there are (broadly) two types of MHC.

The kind of MHC in this case is found on almost all nucleated cells. What's supposed to happen is that any/all of the proteins made in a cell get broken down into peptides at some rate and some of these peptides get presented on the MHC. It's kind of an ID card for cells. If the cell is infected with a virus, then viral peptides can make their way into the MHC. Killer T cells (CD8+ in the paper) will recognize the foreign peptide and kill the presenting cell. Obviously (?) viruses have been around a while and have ways to get around this to some degree. Or they wouldn't be here.

The way they worked the presentation in the paper was to put the influenza genes onto another virus, vaccinia. Vaccinia is the virus used to immunize for smallpox. It's pretty wimpy overall. They infect people with the recombinant vaccinia virus, the immune system responds against it, including the recombinant influenza proteins.

Yes, there's some concern about what this infection might do by itself. You wouldn't want to give this to someone with a severe immune deficiency for example. That's why you do trials.

In this specific case, the recombinant virus shouldn't be in danger of being a 'super virus' because of the way vaccinia replicates vs the way influenza replicates. They're very very different viruses and the function of NP has little use in vaccinia replication.

 

[disappoint]

No, influenza can kill millions of people.

http://virus.stanford.edu/uda/

http://en.wikipedia.org/wiki/Influenza_pandemic

While MOST influenza outbreaks are fairly mild, people still die every year from it.

So now they will just die of pneumonia instead. If you are that close to death that the flu kills you your days are numbered anyway.

 

[alanwest09872]

There's already a demonstration of this with HIV. Most HIV proteins seem to have a bit of room to mutate and thus no longer get presented on MHC, ie there are 'escape mutants.' But there's one particular part of one particular protein that isn't so tolerant of mutations. People whose MHC can present that peptide mount a much more effective response against the infection.


Correct.


Yes, there are (broadly) two types of MHC.

The kind of MHC in this case is found on almost all nucleated cells. What's supposed to happen is that any/all of the proteins made in a cell get broken down into peptides at some rate and some of these peptides get presented on the MHC. It's kind of an ID card for cells. If the cell is infected with a virus, then viral peptides can make their way into the MHC. Killer T cells (CD8+ in the paper) will recognize the foreign peptide and kill the presenting cell. Obviously (?) viruses have been around a while and have ways to get around this to some degree. Or they wouldn't be here.

The way they worked the presentation in the paper was to put the influenza genes onto another virus, vaccinia. Vaccinia is the virus used to immunize for smallpox. It's pretty wimpy overall. They infect people with the recombinant vaccinia virus, the immune system responds against it, including the recombinant influenza proteins.

Yes, there's some concern about what this infection might do by itself. You wouldn't want to give this to someone with a severe immune deficiency for example. That's why you do trials.

In this specific case, the recombinant virus shouldn't be in danger of being a 'super virus' because of the way vaccinia replicates vs the way influenza replicates. They're very very different viruses and the function of NP has little use in vaccinia replication.

I hate when people use the word shouldn't wont is a much better word. shouldn'ts happen all the time.

 

[Mr. Pedantic]

So now they will just die of pneumonia instead. If you are that close to death that the flu kills you your days are numbered anyway.

Yes, why bother having emergency departments, ICUs, or operating rooms? Why bother having hospitals? Why bother having doctors? Obviously if you die from something you were meant to go anyway.

The way they worked the presentation in the paper was to put the influenza genes onto another virus, vaccinia. Vaccinia is the virus used to immunize for smallpox. It's pretty wimpy overall. They infect people with the recombinant vaccinia virus, the immune system responds against it, including the recombinant influenza proteins.


Yes, there's some concern about what this infection might do by itself. You wouldn't want to give this to someone with a severe immune deficiency for example. That's why you do trials.


In this specific case, the recombinant virus shouldn't be in danger of being a 'super virus' because of the way vaccinia replicates vs the way influenza replicates. They're very very different viruses and the function of NP has little use in vaccinia replication.

I see. This makes sense now. Thanks

 

[Gibsons]

I hate when people use the word shouldn't wont is a much better word. shouldn'ts happen all the time.

Depends on your level of confidence. I'd gladly bet money that this approach is about as safe as any attenuated vaccine, like measles or whatever, but there's always room for doubt.