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PostPosted: Tue Mar 02, 2010 12:15 pm 
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niman wrote:
Yes, there is a definite cause for concern, which has been GROSSLY underplayed by agencies and the media. The parallels between 2009 and 1918 are striking and the fact that vaccine against 1918 is more effective than the vaccine against 2009 in mouse challenge experiments using the 2009 virus should be an eye opener.


Greetings from Oklahoma. I have been following this site for quite some time, but am just now deciding to post.

My question is this:

1) Since a 1918 type pandemic is of great concern , and 2) People who have antibodies from the 1918 type virus have some protection from the current H1N1

Why would the CDC not just make the vaccine based on the 1918 virus to start with??? That way if 225G or whatever changes occur that cause it to be like the severe H1N1 would be covered in advance?

If this should be a separate thread please delete or move. Thanks


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PostPosted: Tue Mar 02, 2010 12:26 pm 
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Clint3200 wrote:
niman wrote:
Yes, there is a definite cause for concern, which has been GROSSLY underplayed by agencies and the media. The parallels between 2009 and 1918 are striking and the fact that vaccine against 1918 is more effective than the vaccine against 2009 in mouse challenge experiments using the 2009 virus should be an eye opener.


Greetings from Oklahoma. I have been following this site for quite some time, but am just now deciding to post.

My question is this:

1) Since a 1918 type pandemic is of great concern , and 2) People who have antibodies from the 1918 type virus have some protection from the current H1N1

Why would the CDC not just make the vaccine based on the 1918 virus to start with??? That way if 225G or whatever changes occur that cause it to be like the severe H1N1 would be covered in advance?

If this should be a separate thread please delete or move. Thanks

Welcome Clint3200,

There are several reasons for not selecting the 1918 pandemic strain as a target. First, teh challenge result was unexpected and published this year. Earlier data indicated 1918 patients had antibodies that recongized the 2009 virus, but that data didn't indocate the 1918 target would be a better target for 1009.

Second, the California/7 targte was selected in April, when the sequence database was small, and it wasn't clear that California/7 was relatively rare.

Third, even if California/7 was known to be relatively rare, the sequence would still be much closer to the 2009 consensus sequence than the 1918 sequence.

Fourth, it is still unclear why the 1918 vaccine works well against 2009.

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PostPosted: Tue Mar 02, 2010 12:54 pm 
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Thanks for the response.

With the number of low reactors to the current vaccine, it sure seems to be a brain-fart of major proportions to not select a more recent variant (ie one with 225G) for the next batch of vaccine.


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PostPosted: Tue Mar 02, 2010 3:19 pm 
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Location: South Dakota, USA
Clint3200 wrote:
Thanks for the response.

With the number of low reactors to the current vaccine, it sure seems to be a brain-fart of major proportions to not select a more recent variant (ie one with 225G) for the next batch of vaccine.



Welcome, Clint3200!

You know, I keep wondering about this myself. I wonder if they seriously considered some of the variants - and why they were obviously thrown out as sources. I guess we likely won't ever be privy to the detailed discussions that must have taken place, but I have to say that I am somewhat surprised it remained the same. It just doesn't make sense to me when we have scientists who have provided valuable analysis for them to consider.


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PostPosted: Tue Mar 02, 2010 3:33 pm 
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Clint3200 wrote:
Thanks for the response.

With the number of low reactors to the current vaccine, it sure seems to be a brain-fart of major proportions to not select a more recent variant (ie one with 225G) for the next batch of vaccine.

Dr Niman already preconized in the past vaccine targets different from those officialy chosen for
seazonal influenza in a number of instances.

This critical review on vaccine target choice criteria is expressed in a recent paper (1), and probably also in other papers.

However, given the reigning paradigma of “random mutations”, the very idea of producing a vaccine
not based on a a typical existent strain is unlikely to be contemplated.

Moreover, the concept of formulating a vaccine for a predicted change is conceptually "unthinkable",
since genetic changes are assumed to be random, and therefore non predictable.

Apparently the vacine target selection for poandemic H1N1 followed essentially the same standard modus operandi
already used on the past seasonal flu vaccines.

Emergence and Fixing of Antiviral Resistance in Influenza A Via Recombination and Hitch Hiking
Nature Preceedings (Received 29 January 2009)
http://precedings.nature.com/documents/2832/version/1


Last edited by neuromedia on Tue Mar 02, 2010 3:35 pm, edited 1 time in total.

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PostPosted: Tue Mar 02, 2010 3:34 pm 
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Location: Pittsburgh, PA USA
Commentary

http://www.recombinomics.com/News/03021 ... loppy.html

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PostPosted: Tue Mar 02, 2010 4:44 pm 
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rml wrote:
You know, I keep wondering about this myself. I wonder if they seriously considered some of the variants - and why they were obviously thrown out as sources. I guess we likely won't ever be privy to the detailed discussions that must have taken place, but I have to say that I am somewhat surprised it remained the same. It just doesn't make sense to me when we have scientists who have provided valuable analysis for them to consider.

My only explanation to this surprising choice is a perception by the responsible scientific body that influenza viruses can evolve
either by antigenic shift (reassortment), or antigenic drift, and the latter was supposed to occur at a pace similar to seasonal flu (slow) evolution.

There is nothing in the standard textbooks to conceptually fill the intermediate area between antigenic shift and (slow) antigenic drift.
Since the [rare] antigenic shift had already occurred at the pandemic origin, the virus was constrained to evolve via antigenic drift.

I think the possible conceptual flaw was the hypothesis that a reassortant (pandemic) flu would evolve in a similar rate as the seasonal flu.
Bearing in mind such underliyng hypothesis, the chioce of an early pandemic “wild type” (California/07) would appear as a technically balanced choice.

Trouble was: the virus apparently did not agree with this theoretical model!


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PostPosted: Tue Mar 02, 2010 9:32 pm 
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It's good to see some new people posting. Welcome to the board, Clint3200. Thanks for de-lurking.
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PostPosted: Tue Mar 02, 2010 9:44 pm 
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neuromedia wrote:
rml wrote:
You know, I keep wondering about this myself. I wonder if they seriously considered some of the variants - and why they were obviously thrown out as sources. I guess we likely won't ever be privy to the detailed discussions that must have taken place, but I have to say that I am somewhat surprised it remained the same. It just doesn't make sense to me when we have scientists who have provided valuable analysis for them to consider.

My only explanation to this surprising choice is a perception by the responsible scientific body that influenza viruses can evolve
either by antigenic shift (reassortment), or antigenic drift, and the latter was supposed to occur at a pace similar to seasonal flu (slow) evolution.

There is nothing in the standard textbooks to conceptually fill the intermediate area between antigenic shift and (slow) antigenic drift.
Since the [rare] antigenic shift had already occurred at the pandemic origin, the virus was constrained to evolve via antigenic drift.

I think the possible conceptual flaw was the hypothesis that a reassortant (pandemic) flu would evolve in a similar rate as the seasonal flu.
Bearing in mind such underliyng hypothesis, the chioce of an early pandemic “wild type” (California/07) would appear as a technically balanced choice.

Trouble was: the virus apparently did not agree with this theoretical model!

Actually, I don't think the selection of California/7 was that complicated. The first series of isolates were from southern California. California/7 was from the father (54M) of one of the early cases, but not the first two. The initial California sequences were similar to each other as well as Texas, so the CDC ran with that series (sub-clade). As more isolates were identified, it became clear that California/7 was a minor sub-clade, but work on getting clones and getting the virus to grow well in eggs was already underway, so development continued. In addition, antigenic characterization tests also indicated that California/7 antisera cross reacted with the other clade.

However, it was the more recent data that showed at the single nucleotide change could create a "low reactor" which was a big red flag that the California/7 target would be a problem, and the latest data on vaccine failures suggest there is a big problem.

Sequence data will help determine if the big problem is due to California/7 or a major change, but in either case, the comments on use of California/7 inventory, signaled a strong tendancy to ignore real data and continue with the same old, same old, which is guaranteed to fail.

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PostPosted: Tue Mar 02, 2010 10:48 pm 
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niman wrote:
The first major problem is the selection of California/7. It has 5 differences or more with the vast majority of H1N1 isolates, becasue it represents a rare sub-clade. The antigenic characterization tests are relative insensitive, so the other isolates appear OK, but they are right at the brink of becoming a low reactor. Thus, a single change linked D225G or G158E creates a low reactor, which creates significant vaccine failure.

Moreover, the virus evolves away from the immunity generated in the first two waves, and in doing so, creates a more virulent strain (which likley has D225G/N), leading to more severe cases like the latest SARI cases.


I have read of this here only recently. When were these 5 differences discovered and by whom? What was the "official" eg WHO and CDC reaction?


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