Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

[Giuseppe]

From World Health Organization (http://www.who.int/entity/csr/diseas...te20080214.pdf)
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[HenryN]

Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

http://www.who.int/csr/disease/avian...te20080214.pdf

Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines
February 2008

[Aeolus]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Is a recommendation this specific normal or are they showing their hand?

[HenryN]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Is a recommendation this specific normal or are they showing their hand?

They are showing a losing hand. H5N1 in Egypt has the vaccine selectors beat by a long shot.

[AlaskaDenise]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Are the recommendations be based partly on unpublished sequences?

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[HenryN]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Are the recommendations be based partly on unpublished sequences?

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No, the sequences are published, but the selection is significantly lagging. I will be doing a series of commentaries.

[HenryN]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Commentary

http://www.recombinomics.com/News/03040801/H5N1_Vaccine_2008.html

[AlaskaDenise]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Commentary

http://www.recombinomics.com/News/03...cine_2008.html

Commentary

H5N1 Evolution Outpaces Pandemic Vaccine Selection

Recombinomics Commentary 03:58
March 4, 2008

WHO has published its latest update on “Antigenic and genetic characteristics of H5N1 virus and candidate vaccine viruses developed for potential use as human vaccines." Although it is dated February, 2008, it is already clearly out of date. H5N1 is rapidly evolving as evidenced by 8 vaccine targets already approved (in red in the phylogenetic tree in Figure 1 on page 5), the four targets developed and waiting approval (in blue) and the three selected for development (in green). The tree in this year's report is more complex than the tree from a year and a half ago.

However, in the rapidly evolving clade 2.2 which was been reported in approximately 50 countries west of China, the selections are significantly lagging H5N1 evolution. The approved isolates are from 2005 and include one of the original Qinghai isolates from China in the spring of 2005, an isolate from Mongolia in the summer of 2005, and an isolate from Turkey in the fall of 2005. These three were followed by an isolate from India in the winter of 2006, which is awaiting approval. Although Europe reported little activity in late 2006, early 2007, clade 2.2 was rapidly evolving in Egypt as well as at Uvs Lake in Mongolia in the summer of 2006.

These new and improved versions of H5N1 were easily seen a year ago at the beginning of 2007. The Uvs Lake version appeared in Kuwait in February 2007. Although it was clade 2.2.3, like the Indian isolate, it had evolved markedly, as represented on the tree by isolates from Kuwait and Krasnodar. This evolved version of clade 2.2.3 has now spread throughout Europe, as seen in the recently released sequences from the Czech Republic, Germany, Romania, Saudi Arabia, and Ukraine (as well as reported but unpublished isolates from England, Poland and northeastern Germany). All of these have significantly evolved away from the Indian isolate awaiting approval.

Similarly, the evolution in Egypt has been extensive. Consequently, the tree has five 2007 isolates from Egypt, representing three major branches. One of these five has been selected for vaccine development. The selected isolate is from a mild case in Aswan that had the Mongolian cleavage site. However, the diversity in Egypt a year ago is under-represented on the tree. There are no isolates representing the Gharbiya cluster, which has two receptor binding domain changes, including M230I, which was only detected in fatal cases. Similarly, other sequences from a year ago, including other Gharbiya sequences are also not represented in the published tree.

Thus, the current report has not kept pace with samples collected a year ago. The recent samples from Egypt are significantly more evolved than the sequences represented in the published tree or the early 2007 sequences not represented.

The evolution of H5N1 in India and Bangladesh is not public, and may represent significant additional heterogeneity.

The phylogenetic tree in the latest report is clearly dated, and the vaccine targets are lagging further because of production and approval issues.

H5N1 obviously knows how to evolve more rapidly than the WHO vaccine selection committee.


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[AlaskaDenise]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

....targets are lagging further because of production and approval issues.

What is that timeline? What should it be to keep pace with viral changes?

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[tropical]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

"The phylogenetic tree in the latest report is clearly dated, and the vaccine targets are lagging further because of production and approval issues.
H5N1 obviously knows how to evolve more rapidly than the WHO vaccine selection committee."

The same slow process used for seasonal flu vaccine selection, probably.

[Giuseppe]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

The complete PDF text (with tables) is already posted in this forum at http://www.flutrackers.com/forum/sho...80&postcount=1 -


This link is no longer good. I have merged the threads. Fla1

[HenryN]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

What is that timeline? What should it be to keep pace with viral changes?

.

There is no reason to take a year to identify key sequences. H5N1 evolution involving wild birds and recombination is quite predictable.

[HenryN]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Commentary

http://www.recombinomics.com/News/03070801/H5N1_Vaccine_Qinghai.html

[Niko]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

Commentary

http://www.recombinomics.com/News/03...e_Qinghai.html

<big><big>Commentary </big></big>

H5N1 Pandemic Vaccine Selection Trails Clade 2.2 ChangesRecombinomics Commentary 13:27
March 7, 2008

The recently released human vaccine target selections by the WHO, raise concern over timely identification of targets. H5N1 is rapidly evolving and clade 2.2 is rapidly spreading. The spread of the Uvs Lake strain of clade 2.2.3 has been most glaring, yet this strain was not targeted in the February, 2008 update. The strain has spread throughout Europe and is in the Middle East. Movement into south Asia is unclear, because sequences have not been released. However, earlier sequences were clade 2.2.3, so the spread of the Uvs Lake strain to that region is certainly possible. In addition to the lack of targeting of the Uvs Lake strain, the explosion in diversity in Egypt is under-representation. In Egypt human cases have been reported in each of the last three seasons, moving Egypt to the number one position in confirmed human H5N1 cases outside of southeastern Asia.

As seen in the phylogenetic tree in Figure 1 of the report, the Uvs Lake strain, as represented by isolates from Kuwait and Krasnodar has evolved away from the 2006 clade 2.2.3 isolate from India, which has been selected as a target sequence. The evolutionary movement has been noted for some time, and the spread throughout Europe was emerging in the summer of 2007. The emergence and evolution of the strain was evident in wild bird sequences from the massive outbreak at Uvs Lake in northern Mongolia in the summer of 2006. H5N1 was isolated from a whooper swan and golden eye in Mongolia along with isolates from a duck and grebes in adjacent Tyva in southern Siberia. The sequences were 2.2.3, but were distinct from 2.2.3 isolates from Europe earlier in the year.

As seen in the recently released sequences from the 2006 outbreak in south Korea, the Uvs Lake strain migrated southeast to south Korea near the end of 2006. The sequences also migrated to southwest to Kuwait in early 2007, raising the possibility that it also migrated due south into south Asia.

Although the strain was not reported in Europe in late 2006 or early 2007, it appeared in the Czech Republic in the summer of 2007, as confirmed by the recently released sequences. However, movement into Europe was also indicated by the outbreaks in Germany over the summer. Early reports from FLI indicated the sequences in Germany were most closely related to the published wild bird sequences from Uvs Lake. The German wild bird outbreaks were followed by outbreaks in France, which were also characterized as being closely related to the Uvs Lake of Kuwait sequences. Thus, in the summer of 2007 it was becoming increasingly apparent that Uvs Lake H5N1 was widespread in wild bird populations and was spreading across Europe, displacing early clade 2.2.1 and 2.2.2 strains identified in 2006.

Public confirmation of the spread was provided by sequences from Krasnodar, which were released shortly after the September outbreak. This was followed by release of sequences from Germany, as well as sequences from Romania, which were released shortly after the fall outbreak there. More recent sequences from Saudi Arabia and Ukraine confirm the spread of the Uvs Lake strain in Europe and the Middle East, yet there is no representation in the vaccine targets selected in the recent WHO report.

Similarly, the broad diversity of sequences is under represented in the tree and selection of new targets. In early 2006, clade 2.2.1 sequences were detected in Egypt. These sequences were closely related to sequences in Israel, Gaza, and Djibouti. The sequences from the 2006/2007 had the same regional markers, but were markedly more complex due to acquisition of new polymorphisms. These new polymorphisms trace back to early clade 2.2 isolates, including an over representation of polymorphisms in Germany. This diversity is represented in part by the five Egyptian sequences on the tree. However, the initial cases in the 2006/2007 season were fatal and mapped to additional branches which are not represented on the tree in Figure 1. All patients with M230I died, yet the isolates with M230I are not represented in the tree. Included in the fatal cases with M230I were the three family members designated as the Gharbiya cluster. These patients had another receptor binding domain change, V223I, which is also not represented.

The diversity in Egypt may have contributed to the vaccine failure in some flocks. H5N1 from these isolates is also not represented. These isolates had a large number of non synonymous changes, and were geographically diverse, but primarily in northern Egypt. Similarly, a large number of isolates with M230I and V223I were also detected in the current season. Thus, this season H5N1 is more diverse and unlikely to be well represented by the target sequence from Egypt, which is from a mild case that was genetically distinct from the sequences in northern Egypt. The added diversity in Egypt, coupled with more aggressive human cases will create new challenges for effective human vaccines, which is being exacerbated by vaccine failures and growing diversity in Egypt.

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[kent nickell]

Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines

A few things I found interesting in this document (Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines February 2008) ... especially in light of the recent swan in Japan showing 2.3.2 and 2.3.4 characteristics...

""Clade 2.3.4 viruses have been responsible for human infections in China, Lao People's Democratic Republic, Myanmar and Viet Nam.""

Vaccine development for 2.3.4 includes A/Anhui/1/2005 (CDC), A/Japanese white-eye/Hong Kong/1038/2006 (SJ/NIAID), A/duck/Laos/3295/2006 (FDA) and for 2.3.2 A/Common Magpie/Hong Kong/5052/2007 (SJ/NIAID)

As Dr. Niman has pointed out the virus in the swan in Japan appears to have significantly changed from these isolates....

Also of interest is a collaboration between CDC and NIV (National Institute of Virology, India) for a 2.2 A/Chicken/India/NIV 33487/2006