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**gsgs** · February 15, 2008, 01:06 AM

Re: CDC Recommended Flu Composition for 08/09 Season

but USA reported 96% match of the H1N1 component with
A/Solomon Islands/3/2006 and EISS reported a 95% match.
So, why change it ?

maybe it's not so good to have the same vaccine in the whole world
when there are regional differences.

You might want to take 2 shots next year : one with the new
vaccine, one with the old components from this season -
is it still available next year ?

trivalent is not enough for 5 circulating strains.

**Giuseppe** · February 15, 2008, 05:01 AM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by Florida1 View Post

Recommended composition of influenza virus vaccines for use in the 2008-2009 northern hemisphere influenza season

It is recommended that vaccines for use in the 2008-2009 influenza season (northern hemisphere winter) contain the following:
? an A/Brisbane/59/2007 (H1N1)-like virus;
? an A/Brisbane/10/2007 (H3N2)-like virus;*
? a B/Florida/4/2006-like virus.#

* A/Brisbane/10/2007 is a current southern hemisphere vaccine virus.
# B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) are current southern hemisphere vaccine viruses.
For more information

Recommended composition of influenza virus vaccines for use in the 2008?2009 influenza season [pdf 103kb]

For those interested, a complete WHO Report for recommended composition of seasonal influenza vaccines, with update on influenza activity around the world and antigenic characterization of isolates, tables are available in this forum 'Seasonal influenza update' thread, post #15, http://www.flutrackers.com/forum/sho...8&postcount=15.
--

**gsgs** · February 15, 2008, 07:02 AM

Re: CDC Recommended Flu Composition for 08/09 Season

I made a picture for you of the H1N1 around:

http://magictour.free.fr/panflu/H1N1ALL4.GIF

one virus-hemagglutinin per line, 1075 in total.
"Brisbane" is the new vaccine for 2008/9.
"Solomon" is the old vaccine from this season.

most of the H1N1 in USA last season was a different strain,
but maybe well covered nevertheless.

in which strain does Tamiflu-resistance occur ?
ahh, they have an asterisk in the WHO document
from ironorehopper's link:
A/Paris/577/2007(H1N1)
A/Norway/1735/2007(H1N1)
are Tamiflu-resistant.

I have none of the serum-testing strains included yet,
lanl is down actually, maybe later.
But included are 5 strains from Greece,2008. They are in the
same group as the vaccine strain.

A/Solomon Islands/3/2006
A/Brisbane/59/2007
A/South Dakota/6/2007

A/Florida/10/2007
A/Paris/658/2007
A/Cambodia/371/2007
A/Hiroshima/96/2007

A/New Jersey/22/2007
A/Thailand/711/2007
A/Lyon/1362/2007
A/Colorado/35/2007
A/Hiroshima/102/2007
A/Paris/577/2007
A/Norway/1735/2007
A/Madagaskar/2293/2007
-------------------

only the first 3 are available (secrecy,...) they are all in the
upper group.

**HenryN** · February 15, 2008, 09:24 AM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by gsgs View Post

I made a picture for you of the H1N1 around:

http://magictour.free.fr/panflu/H1N1ALL4.GIF

one virus-hemagglutinin per line, 1075 in total.
"Brisbane" is the new vaccine for 2008/9.
"Solomon" is the old vaccine from this season.

most of the H1N1 in USA last season was a different strain,
but maybe well covered nevertheless.

in which strain does Tamiflu-resistance occur ?
ahh, they have an asterisk in the WHO document
from ironorehopper's link:
A/Paris/577/2007(H1N1)
A/Norway/1735/2007(H1N1)
are Tamiflu-resistant.

I have none of the serum-testing strains included yet,
lanl is down actually, maybe later.
But included are 5 strains from Greece,2008. They are in the
same group as the vaccine strain.

LANL is up, and the analysis of the six public sequences with H274Y is very straightforward and easily visualized in a phylogentic tree using free public software.

Three of the isolates

CY027037 A/Kansas/UR06-0104/2007 NA (6) 1427 2007 H1N1
ISDN282240 A/Minnesota/23/2007 NA (6) 1413 2007 H1N1
ISDN263890 A/Texas/31/2007 NA (6) 1413 2007 H1N1

are New Caledonian-like, as indicated in the associated LANL charaterization sheets.

the other three

ISDN282211 A/Hawaii/21/2007 NA (6) 1413 2007 H1N1
ISDN282224 A/Hawaii/28/2007 NA (6) 1413 2007 H1N1
ISDN282222 A/Hawaii/28/2007 NA (6) 1413 2007 H1N1

are very closely related to the Brisbane 59 strain, which is also supported by serological evidence of the unpublished isolates.

Thus, the acquistion of H274Y represnts at least two independent events that place H274Y on two very different H1N1 genetic backgrounds.

These results parallel G743A, which is an NA polymorphism that appeared concurently on multiple H5N1 genetic backgrounds.

http://precedings.nature.com/documents/459/version/3

These data are NOT easily explained by adaptive random mutations, which is the current dogma on influenza evolution.

Consequently, the influenza "experts" will continue to be "startled" by influenza evolution (although they seem to have outgrown fears of falling off the earth's edge, so there is some hope).

**HenryN** · February 15, 2008, 10:40 AM

Re: CDC Recommended Flu Composition for 08/09 Season

Commentary

Concurrent Acquisition of Tamiflu H274Y on H1N1 Subclades

http://www.recombinomics.com/News/02150801/H274Y_Concurrent.html

Recombinomics Commentary

**HenryN** · February 15, 2008, 08:25 PM

Re: CDC Recommended Flu Composition for 08/09 Season

http://www.cidrap.umn.edu//cidrap/co...eb1508flu.html

Flu widespread in 44 states, CDC reports

Robert Roos News Editor

Feb 15, 2008 (CIDRAP News) ? The current influenza season is showing signs of becoming a tough one, with flu activity now widespread in 44 states and many of the circulating viruses differing from those in the vaccine, the Centers for Disease Control and Prevention (CDC) reported today.
Dr. Joe Bresee, chief of the epidemiology and prevention branch in the CDC's Influenza Division, said it's too early to tell if this season will be unusually bad, but so far it is looking worse than the past two or three seasons, which were relatively mild.
Speaking at a news briefing, Bresee said influenza A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B.
The CDC released more evidence today that many H3N2 and B viruses making people ill differ from the strains in the vaccine, though the H1N1 viruses continue to match the vaccine. The agency first reported the problem last week.
The agency also reported that 4.6% of all the flu viruses analyzed so far showed signs of resistance to oseltamivir (Tamiflu), the most commonly used antiviral flu drug. That represents a "real increase" in resistance but is not yet a major worry, Bresee said.
So far this season, 10 children have died of flu, 9 of them since Jan 1, Bresee reported. Four of those children had Staphylococcus aureus coinfections, a complication that the CDC recently asked physicians to watch for and report.
Flu spreading nationwide
For the week that ended Feb 9, 44 states reported widespread flu activity and 5 reported regional activity, according to today's CDC report, a Morbidity and Mortality Weekly Report (MMWR) early release. By comparison, in the last three seasons the number of states reporting widespread or regional activity peaked at between 41 and 48.
In another sign of a worsening epidemic, 33% of specimens tested for flu last week were positive, the report says. In the previous three seasons, the peak percentages of positive specimens ranged from 23% to 28%. Also, 5.7% of all outpatient visits to sentinel healthcare providers last week were for influenza-like illness. The peak percentage of visits for flu-like illness in the last three seasons never exceeded 5.4%.
Bresee said the current epidemic looks worse than the past two or three in terms of hospitalizations and deaths. However, "It's not an atypical season if you look back over many years," he said.
"The reasons are probably multiple, but you can't discount the fact that in seasons where we have a predominant H3N2 virus in circulation, we tend to have more disease in those seasons," Bresee said.
Since Sep 30, the CDC has subtyped 2,299 influenza A viruses and found that 55% were H3N2 and 45% were H1N1, the MMWR report says. H1N1 viruses predominated through mid-January, but H3N2 strains have taken over since then, it states.
Not a great year for the vaccine
The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved from the H3N2 strain in the vaccine?A/Wisconsin/67/2005. Yesterday the World Health Organization (WHO) recommended that the Brisbane strain replace the Wisconsin strain in next season's northern hemisphere vaccine.
Of 68 type B viruses characterized by the CDC, only 4 (6%) belonged to the B/Victoria lineage represented in the vaccine, and only 1 of the 4 was the same strain as in the vaccine (B/Malaysia/2506/2004). The other 64 isolates (94%) belonged to the Yamagata lineage, the CDC reported.
In contrast, the circulating H1N1 viruses continue to match up well with the vaccine. Of 117 isolates tested, 107 (91%) were similar to the vaccine strain, A/Solomon Islands/3/2006-like, the MMWR report says.
Concerning the circulating H1N1 viruses, the CDC report contrasts with yesterday's WHO report. The WHO said "the majority" of recent H1N1 isolates tested globally differed from the Solomon Islands strain and were similar to a strain known as A/Brisbane/59/2007. The WHO advised using the latter in next year's vaccine.
Overall, said Bresee, "Slightly more than half of the viruses we looked at in our lab are somewhat different from the vaccine strains and may not be well covered by the vaccine strains." But what percentage of the viruses in circulation are not covered by the vaccine is unknown, since the isolates tested by the CDC aren't necessarily a representative sample, he said.
Bresee said the vaccine still should provide some protection despite the mismatches with two of three circulating strains.
Ideally, a vaccine that covers the circulating strains should provide 70% to 90% protection, he said. Under the circumstances, "We'd expect the 70 to 90% to be a bit lower this year. . . . Even in years when the vaccine virus doesn't match perfectly against the circulating strains, we do see some effectiveness. This is particularly important in patients who have conditions where they're more likely to get severely ill."
Bresee said the CDC has heard anecdotal reports of flu cases in people who had been vaccinated, but that's not unusual for any year. "Even in years when the vaccine matches less well against the circulating strains, we know the vaccine will tend to make the illness milder," he added.
Tamiflu resistance increases
The CDC has tested 350 flu viruses and found that 16 (4.6%) had a mutation that confers resistance to oseltamivir, according to today's report. All the resistant isolates were H1N1; they made up 8.1% of the 198 H1N1 viruses tested. In contrast, less than 1% of H1N1 viruses tested last years showed resistance. The increased resistance to the drug was first reported about 2 weeks ago.
"The level [of resistance] we're seeing is certainly higher than we've seen in the past, and we think it's a real increase," Bresee said. But he said the overall resistance levels are still considered very low and certainly not high enough to warrant changing the CDC's recommendation to use oseltamivir to treat flu patients. There have been no reports of increased resistance to zanamivir (Relenza), the other drug in the class known as neuraminidase inhibitors.
Resistance to the older flu drugs, amantadine and rimantadine, remains high this season, and the CDC continues to advise against using them for flu, the CDC report says.
Deaths in children
Concerning the 10 children who have died of flu so far this season, Bresee said, "We've seen somewhere between 44 and 73 cases in the last 3 years, so the finding of 10 this late in the season is not totally unexpected. We may see more before the season is finished."
Saying the 10 deaths are still under investigation, Bresee couldn't list which flu subtypes were involved.
See also:
Feb 15 MMWR update on flu activity
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm57e215a1.htm?s_cid=mm57e215a1_e
Feb 14 CIDRAP News story "WHO advises total makeover for 2008-09 flu vaccine"
Feb 8 CIDRAP News story "CDC says influenza B strain doesn't match vaccine"
Feb 7 CIDRAP News story "Europe reports further increase in Tamiflu resistance"

**Oracle** · February 15, 2008, 10:48 PM

Re: CDC Recommended Flu Composition for 08/09 Season

"These data are NOT easily explained by adaptive random mutations, which is the current dogma on influenza evolution."

Can you please patiently explain your theory (again), in a bit more detail. Are these energetically (thermodynamically) favored synonymous changes (a fixed number of the higher frequency changes)?

**HenryN** · February 16, 2008, 03:01 PM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by Oracle View Post

"These data are NOT easily explained by adaptive random mutations, which is the current dogma on influenza evolution."

Can you please patiently explain your theory (again), in a bit more detail. Are these energetically (thermodynamically) favored synonymous changes (a fixed number of the higher frequency changes)?

I'm not sure what you are asking. the quote is quite straightforward. The adaptive mutations would require do novo H274Y formation in the presence of Tamiflu. However, H274Y is not in countries with high Tamiflu use (Japan), is being transmitted to patients not on Tamiflu, and doesn't have the expected fitness penalty.

The latest media report describes TEN patients in Chicago, with EIGHT from ONE facility.

For the entire season the US has reported 16, so 10 more is quite a jump.

**gsgs** · February 16, 2008, 03:57 PM

Re: CDC Recommended Flu Composition for 08/09 Season

no new formation of H274Y mutations is required.
Just Tamiflu reduces the already circulating 274H strains
while favouring the already circulating (but rare before 2008)
274Y strains in the competition of viruses.

Reducing the spread of non-resistant flu increases the
spread of resistant flu.

I'm not sure, how big that effect can be, though.
They should run it through their modeling software.

**Niko** · February 16, 2008, 04:00 PM

Re: CDC Recommended Flu Composition for 08/09 Season

Just an FYI...
Only a tiny fraction (% unknown) of flu suspects are ever tested. In the very busy private pediatric office where I take my children, they have 7 MDs and 3 Physician Assistants and many nurses - as of last week, they had not tested a single case of suspected flu this season. I was told they don't test.

**HenryN** · February 16, 2008, 04:51 PM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by gsgs View Post

no new formation of H274Y mutations is required.
Just Tamiflu reduces the already circulating 274H strains
while favouring the already circulating (but rare before 2008)
274Y strains in the competition of viruses.

Reducing the spread of non-resistant flu increases the
spread of resistant flu.

I'm not sure, how big that effect can be, though.
They should run it through their modeling software.

Please.

H274Y is spreading in countries that rarely use Tamiflu, which is why the "experts" were "startled".

Lets stick to the data instead of "theories" that have some MAJOR problems (and H274Y in New Caledonia and Brisbane points toward independent introductions).

**AlaskaDenise** · February 16, 2008, 09:30 PM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by niman View Post

Commentary

http://www.recombinomics.com/News/02...oncurrent.html

Commentary

Concurrent Acquisition of Tamiflu H274Y on H1N1 Subclades

Recombinomics Commentary 15:26
February 15, 2008

The sudden appearance of the oseltamivir (Tamflu) resistance marker H274Y on seasonal H1N1 from residents in countries where oseltamivir usage is low, has created problems for explanations invoking adaptive mutations. There have not been reports of recent changes in oseltamivir usage for treatment of seasonal flu, and the country with the highest reported use, Japan, has been negative for the change in the most recent 71 isolates tested. Moreover, the resistance is limited to H1N1 and involves the same change, H274Y.

The report on vaccine selection for 2009 provides some additional data. Recent human isolates are most closely related to A/Brisbane/59/2007, which is a genetic variant of the current vaccine target, A/Solomon Island/3/2006. The report lists isolates which are more closely related to the Brisbane/59 strain, and two of those isolates, A/Paris/577/2007 and A/Norway/1735/2007 are oseltamivir resistant.

However, NA sequences from six additional oseltamivir resistant isolates from the United States are available at Los Alamos. Three of the isolates are from Hawaii, and phylogenetic analysis shows that they, like the two isolates above, are closely related to the Brisbane strain.

However, the three other isolates (from Kansas, Minnesota, and Texas) are New Caledonia-like, which are distinctly different than either Solomon Island or Brisbane. Thus, the concurrent acquisition of H274Y into seasonal H1N1 involved at least two independent events.

The acquisition of the sample polymorphism onto multiple genetic backgrounds is similar to the acquisition of G743A onto multiple clade 2.2 genetic backgrounds. Like the H274Y acquisitions, the isolates with the change map to the tips of branches on the phylogenetic trees, indicating the acquisitions are recent and independent of acquisitions on other branches.

This type of acquisition is easily explained by recombination with a common donor sequence. For H274Y, there are no reports of dramatic increases in oseltamivir treatment of H1N1 seasonal flu, but there are reports of widespread use of Tamiflu blankets in areas with H5N1, and the most commonly reported change in N1 in H5N1 is H274Y.

.

**AlaskaDenise** · February 16, 2008, 09:39 PM

Re: CDC Recommended Flu Composition for 08/09 Season

Dr. Niman:

I don't understand.

Why is H274Y in US H1N1 if tamiflu blankets for H5N1 are not present in the US?

Why isn't the change in H3N2 or B?

What is the source?

.

**HenryN** · February 17, 2008, 10:03 AM

Re: CDC Recommended Flu Composition for 08/09 Season

Originally posted by AlaskaDenise View Post

Dr. Niman:

I don't understand.

Why is H274Y in US H1N1 if tamiflu blankets for H5N1 are not present in the US?

Why isn't the change in H3N2 or B?

What is the source?

.

H274Y is very effective in N1 at inhibiting Tamiflu. It can be selected in Tamiflu blankets thrown over areas with H5N1. A dual infection allows the H274Y in avian N1 to move to human N1. It probably grabs a few more changes to make the H1N1 evolutionarily fit, so it can out-compete wild type, so now H1N1 with H274Y is transmitting H2H and moving into regions with Brisbane H1N1, which includes the US (earlier it was Hawaii, and now it is clearly in Chicago - and probably VERY widespread, but the sequencers still have to catch up with the outbreaks).