Talk:Flu research

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[edit] Can a cocktail of HA1..HA16 and N1..N9 be used directly as a flu vaccine with a promoter?

Can a cocktail of HA1..HA16 and N1..N9 be used directly as a flu vaccine with a promoter?

I've just read in this article that:

"Another technique is use of cell cultures to grow vaccine strains; such as genetically engineering baculovirus to express a gene that encodes an influenza coat protein such as hemagglutinin or neuraminidase. A recent NIAID-supported Phase II clinical trial of a vaccine produced by Protein Sciences Corporation using this strategy showed that it is well tolerated and immunogenic; the company is conducting further clinical evaluation of this product."

It would seem to me that rather than creating a vaccine against a single HA or neuraminidase, it'd make sense to create a vaccine against a COCKTAIL of all 16 HA's and all 9 Neuraminidases (along with a promoter).

Presumably, this might give a very broad initial immunity to the general population which could then - if and only if necessary - be supplemented with the more traditional last minute specialized/ad-hoc vaccines that change every 6 months or so.

Does anyone know if these folks &/or other researchers are doing this ?

Regards, 129.78.64.100 10:58, 20 February 2007 (UTC) G. Holt

You ask:Can a cocktail of HA1..HA16 and N1..N9 be used directly as a flu vaccine with a promoter? The answer is no. Each year a highly specific vaccine is make for the three exact strains most likely to be the major strains, and if the strain is even moderately different, the vaccine doesn't work. So we would need to create a vaccine for every possible stain (trillions at least), not just every possible subtype. Further the vaccine wears off somewhat over time. There is an attempt to create a vaccine using the M2 protein which doesn't mutate much, but as it is underneath the H and N proteins, a relative lack of access to it by antibodies makes the idea iffy. See H5N1 clinical trials for what H5N1 vaccines are under clinical trial.WAS 4.250 22:57, 20 February 2007 (UTC)


[edit] RE : Targeting HA[1..16] and N[1..9] CONSERVED EPITOPES with a Vaccine ?

Thank you for your response above. If I am understanding it correctly, then you're saying that EACH HA subtype (for example HA2) has a very large number of sub-SUB-types, and furthermore, that these sub-SUB-types DO NOT share one or more (identifiable) conserved EPITOPES ?

If this is the case, then I think that I understand your point. If this in NOT the case - eg. if each HA subtype has AT LEAST ONE (or possibly more) epitopes that are shared, (or at least that are highly cross-reactive) then I'm still unclear as to WHY one couldn't (at least in theory) try to create a FOCUSSED immune response directed SPECIFICALLY at those CONSERVED Epitopes (or versus related mimotopes). In theory, then this should provide some immunization against the entire HA-subtype.

Since immune response is massively parallel, presumably, one could create a vaccine that contained one or more conserved epitopes from EACH HA subtype, and (for good measure) versus conserved epitopes from each N subtype with suitable promoters. If this were the case, then presumably, at least in theory, even if lots of other surface proteins on the prevailing virus changed in a combinatorically explosive number of ways, to the extent that those CONSERVED epitopes are still expressed and visible on the viri, wouldn't a stronger/protective immune response still be likely to occur ?

Offhand, I could see how the huge variation of surface proteins might distract the immune response and prevent it from spontaneously generating effective lasting immunity against the FEW conserved epitopes (unless it were ARTIFICIALLY caused to do so). Or perhaps no such conserved epitopes exist ? Or perhaps there are some other things that I'm confused about.

Please let me know. Thank you for your time.

129.78.64.100 10:44, 27 February 2007 (UTC) G. Holt

If you start by believing that "EACH HA subtype (for example HA2) has a very large number of sub-SUB-types, and furthermore, that these sub-SUB-types DO NOT share one or more (identifiable) conserved EPITOPES" then you are at least moving in the right direction. You can refine this by understanding that "subtype" is used with a very specific meaning in Influenzavirus A terminology and the millions of varients (immuniologically significant strains) within each subtype is not called a "sub-sub type" as a matter of terminology. Please take a look at:
You are welcome. If you have additional questions, please first consult some of the above literature. I'm happy to assist you in your research. WAS 4.250 18:32, 27 February 2007 (UTC)


Thank you for the references! I've only had a chance to start looking at a few of them, but I found these very interesting comments in the Influenza report source :

"In influenza infection, the receptor binding site of viral hemagglutinin (HA) is required for binding to galactose bound sialic acid on the surface of host cells (Weis 1988). Certain areas of the binding site of HA are highly conserved between subtypes of the influenza virus (Daniels 1984). " In :

           Binding to the host cells
           Chapter :   Pathogenesis and Immunology 
           by Georg Behrens and Matthias Stoll


"Vaccines to conserved proteins have been considered, and among the candidates are the M2 and the NP proteins. It is hoped that, by producing immunity to conserved proteins, i.e. proteins that do not undergo antigenic change like HA and NA do, a vaccine can be produced that does not need to be "reinvented" each year. This is also on the WHO's agenda for a pandemic vaccine (Couch 2005). Such vaccines have been shown to be effective in laboratory animals, but data are not available for human studies. "Generic" HA-based vaccines, aimed at conserved areas in the protein, are also being considered (Palese 2002b).


              Chapter :      Vaccines 
              by   Stephen Korsman

from

http://www.influenzareport.com/ir/pathogen.htm


Interesting!


I also recently found this article written by a bunch of researchers at the Wistar Institute :

Gerhard W, Mozdzanowska K, Zharikova D. Prospects for universal influenza virus vaccine. Emerg Infect Dis [serial on the Internet]. 2006 Apr [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-1020.htm

Here's the abstract :

"The current vaccination strategy against influenza A and B viruses is vulnerable to the unanticipated emergence of epidemic strains that are poorly matched by the vaccine. A vaccine that is less sensitive to the antigenic evolution of the virus would be a major improvement. The general feasibility of this goal is supported by studies in animal models that show that immunologic activities directed against relatively invariant viral determinants can reduce illness and death. The most promising approaches are based on antibodies specific for the relatively conserved ectodomain of matrix protein 2 and the intersubunit region of hemagglutinin. However, additional conserved determinants for protective antibodies are likely to exist, and their identification should be encouraged. Most importantly, infection and current vaccines do not appear to effectively induce these antibodies in humans. This finding provides a powerful rationale for testing the protective activity of these relatively conserved viral components in humans."

It's pretty recent.

129.78.64.100 07:41, 2 March 2007 (UTC) G. Holt

Above, I told you "There is an attempt to create a vaccine using the M2 protein which doesn't mutate much, but as it is underneath the H and N proteins, a relative lack of access to it by antibodies makes the idea iffy." Since you seem interested in this area of research here is another link http://www.stjude.org/media/0,2561,453_5715_20703,00.html WAS 4.250 10:05, 2 March 2007 (UTC)

[edit] New influenza detection technology

"The FluChip successfully distinguished among 72 influenza strains--including the H5N1 avian influenza strain--in less than 12 hours."[1]69.6.162.160 13:41, 30 August 2006 (UTC)Brian Pearson

After reading the details, I wouldn't call it "successful". Even the for-profit company promoting the FluChip says is four years away from marketing a finished version. At its current best it is wrong an unacceptably high percent of the time. It is admittedly irrelevant to a pandemic strain for the simple reason that a pandemic strain does not yet exist. And the current method can do the same thing more accurately in less than a day in an adequate lab. The method does hold promise for further research tho. And it does illustrate the current state of research and the limitations of current methods (needing a very expensive lab). WAS 4.250 15:04, 30 August 2006 (UTC)

For a technology in its infancy, I would say it looks promising. Also, a big plus is that it doesn't require "high-level biosafety facilities."69.6.162.160 00:40, 3 September 2006 (UTC)Brian Pearson

New technique, if refined and developed, could detect specific viruses in 60 seconds, rather than 12 hours.[2]Brian Pearson 04:16, 20 November 2006 (UTC)

Surface Enhanced Raman Spectroscopy is also backed up by
"This proposal addresses the need for miniature, low power, reagentless, robot-mounted, instruments for real-time detection and classification of trace concentrations of biological and chemical agents on surfaces. Deep UV laser induced native fluorescence (UVLINF) is the most sensitive technique for detection and rough classification of trace amounts of biological and organic materials. Photon Systems has used this technique to demonstrate detection of single spores at a working distance of 30cm. Higher levels of classification specificity can be obtained using deep UV resonance Raman spectroscopy (UVRRS), with similar levels of sensitivity to surface enhanced Raman spectroscopy (SERS), although the sensitivity is less than UVLINF. We propose an advanced, robot-mounted, electro-optical instrument that combines UVLINF and UVRRS for non-contact detection and classification of trace concentrations of biological and chemical agents while requiring no consumables or sample preparation and producing no waste products. At the heart of this instrument is a deep UV laser consuming less than 5W of battery power that simultaneously generates Raman scattering and excites native of fluorophores contained within microorganisms and many organic and inorganic materials. Using an onboard real-time algorithm the UVLINF and UVRRS data are processed to identify and classify contaminants in less than 1 second."Department of Defense contract Awarded: 15aug06
Looks interesting! WAS 4.250 06:21, 20 November 2006 (UTC)
I requested the original article at University of Georgia office of public affairs news service site, since the maze there is sometimes hard for me to navigate, and received this:[3]Thank you, UGA.Brian Pearson 23:48, 20 November 2006 (UTC)

An improvement to the FluChip DNA microarray (based on 3 flu RNA segments) called the Mchip (based on one RNA segment - the Matrix segment) has been reported by the National Institute of Allergy and Infectious Diseases and covered by CIDRAP with the technical abstract at the American Chemical Society’s journal Analytical Chemistry. WAS 4.250 09:04, 20 November 2006 (UTC)

[edit] Treatment 'to neutralise all flu'

"Crowding out the invading influenza" is a possibility. See Treatment 'to neutralise all flu' - 69.6.162.160 00:35, 4 October 2006 (UTC)Brian Pearson

The article says "Professor Nigel Dimmock has spent more than two decades developing the new approach. To create the 'protecting virus' he deleted around 80% of the genetic material of one of the eight RNA segments that make up the flu virus. This deletion makes the virus harmless and prevents it from reproducing by itself within a cell, so that it cannot spread like a normal influenza virus. However, if it is joined in the cell by another influenza virus, it retains its harmless nature but starts to reproduce - and at a much faster rate than the new influenza virus. This fast reproduction rate - spurred by the new flu infection - means that the new invading influenza is effectively crowded out." This is not junk science, but as the article also says "This is cutting edge science, but there is a lot that could still go wrong." WAS 4.250 01:49, 4 October 2006 (UTC)
Another promising approach is the discovery of a peptide which could prevent "numerous subtypes" of flu.[4]If that isn't enough, maybe a combination of approaches would be. 69.6.162.160 02:55, 5 October 2006 (UTC)Brian Pearson
There is enough government money and venture capital available that anyone with an idea is floating it in press releases trying to get funding. Whether any of it will pay off or not is unknown. But traditional approaches are being funded along side new ideas and between Jan 2007 and Jan 2009 the world will see solutions available. I just hope we see solutions before a pandemic rather than after. If the pandemic comes too soon all we'll have is prepandemic vaccines for a few million people that might make a deadly flu into a nondeadly flu for those who get the prepandemic vaccine. WAS 4.250 05:56, 5 October 2006 (UTC)

[edit] New approach helps the immune system

Discovery is a promising advance which could lead to new treatments for Hepatitis C, AIDs, and other chronic viruses.

LIAI's research team used a novel method for tackling a chronic viral infection, which involved releasing the disease-fighting power of the immune system by blocking the interleukin-10 (IL-10) messenger molecule receptor with a simple antibody. Normally, this molecule, which is produced at substantial levels during hepatitis C, HIV and cytomegalovirus infections, acts to suppress the immune system's attack on chronic virus infections. "We thought, 'what if we try to correct what the immune system seems to be doing wrong in response to many chronic viral infections?,'" said von Herrath. "So we unleashed the power of the immune system by using an antibody to block the IL-10 receptor. This taught the immune system to take the right action and fight the disease."

[5]69.6.162.160 01:23, 10 October 2006 (UTC)Brian Pearson

The article also says "One of the next steps will be to test the IL-10 blocking antibody on human cells in the lab to see whether these cells also become normal and functional against the virus and to test combination therapies that add viral vaccines, anti-viral drugs and other antibodies to the IL-10 receptor blockade. Combination therapies bear the promise to minimize potential side effects while achieving synergy in combating the viral disease." A key to helping one decide how much is real and how much is researchers and companies trying to get funding and fame is clinical trials. Are they being done? By whom? Are the results of the clinical trials published? Are those results promising enough that either further tests are to be done or government approvals for patient use are expected? WAS 4.250 06:45, 10 October 2006 (UTC)
The morning after I posted this study, it occurred to me to ask "if we would also need a way to turn IL 10 back on, so it our immune system can fight other diseases as it is designed to do, or if we can safely leave it blocked". Matthias said, "Antibody blockade is always temporary, and the overall immune system will re-equilibrate after such a blockade." - 69.6.162.160
I see you are bringing me back to earth, as usual, WAS 4.250. I'm the optimist whereas you are the skeptic. Could reality be somewhere in the middle? BTW, it appears that they will continue with this research on humans, though I have no idea about the 'funding or fame' question. If I were Mathias, I wouldn't care, so long as I could continue with the research. I've always heard that even negative results can be considered progress -- it is one more thing added to our store of knowledge. - 69.6.162.160
Ants as a group are good at finding food. Individual ants - not so good. As a social species they are evolved to engage in behaviors that are individually reckless but profitable as a whole. Same with humans. So while I have no faith in individual human efforts; I have great faith in our collective efforts. WAS 4.250 03:21, 15 October 2006 (UTC)

[edit] Study: Implications for Influenza Surveillance

"The analysis revealed a picture of flu evolution that was surprisingly different from the prevailing conception of how the virus changes."[6]69.6.162.160 02:00, 28 October 2006 (UTC)Brian Pearson

See Punctuated equilibrium for why the researchers are making a big deal out of a small but important contribution and see Influenzavirus_A#Evolution for where I thought this data should go. It is interesting. But entirely expected in a broad sort of way. WAS 4.250 06:02, 28 October 2006 (UTC)
Regarding "Implications for Influenza Surveillance"; we do have the articles Reporting disease cases and Clinical surveillance, but I can't think of what additions to make to the articles based on this new research. Can you? WAS 4.250 06:08, 28 October 2006 (UTC)
I was unaware of the Clinical surveillance topic, but I could see it going there. At the same time, it appears to still fit under the umbrella of Flu research. The problem is, how. I've searched other possible topics, as you probably have, and not found any good place to put it. But, I've done a bit more reading (almost to the point of getting buried) and found this: Genome Analysis: A Tool to Combat the Influenza Virus[7] This implication I see from this is that they are already doing as much in the way of genome studies as possible, though maybe it can be further expanded and fine-tuned.69.6.162.160 07:28, 31 October 2006 (UTC)Brian Pearson
Also, the Influenza Genome Sequencing Project article could use a section on studies done with the data. WAS 4.250 21:39, 31 October 2006 (UTC)
I was just thinking about the link box in H5N1 under Treatment and prevention for humans. Maybe it could be expanded to include the other topic links you mentions, such as Influenza Genome Sequencing Project and Clinical surveillance. Copies of the expanded version could be posted at all related topics.
As to adding sections, I'm not sure I have the aptitude to write in that style. I'm something of an idea person and I can write -- possibly I could do it, given time. Most of my contributions to Wikipedia have been in the way of minor edits.69.6.162.160 01:43, 1 November 2006 (UTC)Brian Pearson
WAS 4.250, I was going to pursue the first idea, expanding the link boxes, but found I couldn't 'see' it in edit mode.69.6.162.160 00:10, 13 November 2006 (UTC)Brian Pearson
I don't know if that "link box" (nav or navigation box is more customary terminology) should be altered or not; so maybe its a bad idea to help you out here. None-the-less, let's see what happens if I empower you with data ... If you edit an article, below the edit box you will find links to transcluded entities that you can get to by clicking on them. Anytime you see a transcluded template in the edit box like {{Flu}} you can type "Template:Flu" in the search box on the left (above "Go" and "Search") to get to it. The "Template" part is one of several terms available for accessing a designated search space on the English Wikipedia. "Template talk" "Talk" "Wikipedia" "Wikipedia talk" "User" and "User talk" are others that can be used prior to a colon and a search term. I forget the rest. WAS 4.250 04:27, 13 November 2006 (UTC)

This is what I thought about doing:

Flu

BTW, I noticed the image is disappearing after the page loads. I tried but failed to figure out how to make it stick. I right-clicked the image and copy-pasted the file name, here, but you'll probably have to hit 'edit' before you can see it. I haven't been able to get it to remain visible, otherwise.: [8]Brian Pearson 07:22, 14 November 2006 (UTC)Brian Pearson

I had no difficulties in viewing the template. Sometimes there is a issue with "flushing the buffer". Maybe that's what happened to you. I changed "Flu research" to "Flu research" and provided shortened labels for the last two. Otherwise, it seems reasonable. But I have no taste in these matters. You could ask others what they think. Or you could do what I do; do it the wiki way; just boldly make the change and deal with objections from whoever changes it back (if anyone). I don't object to your proposed change. Nor do I love it enough to implement it myself. Nor do I dislike it enough to revert it if you implement it. I'm easy. You seem like a cautious fellow so if you wish to run it by other people, try User talk:TimVickers and/or User talk:Waitak. They are both very excellent people who have helped a lot with the Flu/H5N1 series of articles. Do what feels right for you. WAS 4.250 08:36, 14 November 2006 (UTC)

Thanks. BTW, I thought I'd leave the link off of Flu research since that is the topic, here, and do the same elsewhere. I'm not in any big hurry, though, since I'm a bit busy.69.6.162.160 18:43, 14 November 2006 (UTC)Brian Pearson

[edit] Light activated antimicrobrial/antiviral nano film

"In the presence of light, a specific reaction takes place on the surface that makes the air poisonous to the microbes, yet harmless to people," Michielsen says. "The coating doesn't wear out and continually regenerates so it's able to continue killing viruses again and again."[9] Brian Pearson 05:40, 14 November 2006 (UTC)Brian Pearson

Yeah, wood is a better cutting board than other materials because of its anti-microbe properties and numerous materials have interesting anti-microbe properties under various temperature or lighting or other conditions. The problem is microbes create biofilms, so it doesn't matter what the surface is if it isn't scrubbed down at appropriate intervals (depending on dust, soot, oil in the air, water in the air, etc). WAS 4.250 08:14, 14 November 2006 (UTC)
I asked about this, and got this message: Brian
Since viruses only replicate within other cells, they do not create a biofilm of their own, unlike bacteria. Normal cleaning of the surfaces should suffice.
Regards,
Stephen Michielsen Brian Pearson 15:36, 21 November 2006 (UTC)
The point about biofilms is not that viruses create them (they don't) but that "Light activated antimicrobrial/antiviral nano film" has a problem in being useful because the surfaces it could be used on will need to be regularly cleaned of other stuff (including biofilms from bacteria) anyway, so the viruses will be killed/removed during the cleaning and the antiviral properties become redundant. Sorry I wasn't more clear. I had no idea that you would believe that I believed that viruses create biofilms (they don't). Between cleanings, the virus is blocked from contact with the virus-killing surface by biofilms created by other organisms (depending on dust, soot, oil in the air, water in the air, etc) to some degree depending on what it is used for. WAS 4.250 01:04, 22 November 2006 (UTC)
Yes I agree. I wish he had gone into it more, he did say it would need cleaning. And, I guess if they are used as filters, they can be changed periodically, just as they would the standard types. The stuff may even be used in the operating room for improved masks, aside from the fact that they would still have to be fine enough so that viruses don't slip through the cracks. Just a thought. Brian Pearson 03:38, 22 November 2006 (UTC)
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