2009-11-28

Vaccine Failure Event Confirmed in New York Times by UK national medical laboratory

The coordinated work of several individuals at FluTrackers.com concerning the newspaper report being referenced in this article adds a new layer of concern to the story.  Though several avenues have been attempted to confirm exact details of this report published in the New York Times, no identification has occurred of the laboratory or lab representative making the comment.  Attribution on an item of this import is essential.  The quote parallels the testing results and is perfectly admirable as to candor. 

Though exceptional effort has been expended in learning the source and to no avail as yet, we do have a reasonable justification in thinking that the information was not invented by the New York Times author.  The quote remains in the online version of the article as of 2009-12-01-21:00Z.

At any rate, the details of the following interpretation hold, as no substantive data has been changed.  We have removed the lab name from the title of this report and the body because no one there has claimed responsibility for the comment.  The "low reactor" status persists and that challenge would have logically been against antisera from ferrets raised against the vaccine candidate strain.  That's the purpose of the test, to determine level of cross-reactivity or, more simply, vaccine match.  We are appreciative of the transparent reporting of this early vaccine escape event.

Our original interpretation follows with minor edits for clarity and with removal of the lab name until additional attribution occurs from the New York Times or other new source.

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Updates reflected on the characterisation sheets from the Ukraine indicate antigenic testing against one of the samples.  Of note was the LvivN6 sample from a fatal case with 225G being reported as exhibiting clear vaccine escape signals with a low reactor status update on the antigenicity profile.  That type of information is important news to the world.  We would have expected a news conference or a press release prior to the status update as confirmation of the database detail, but no public health notice of that type has occurred. 

Today, Donald McNeil of the New York Times is reporting that Britain's national medical laboratory has corroborated the status update of "low reactor" as follows:

"One isolate from Ukraine with the mutation had changed so that swine flu vaccine probably would not protect against it well, Britain’s national medical laboratory reported Friday."

Dr. Henry Niman of Recombinomics is concerned that differing opinions have been offered to the public concerning the importance of the D225G polymorphism.  We share that concern about the lack of consistent reporting.  Moreover, a clear finding is required on antigenicity of the remaining Ukraine sequences with a focus on the remaining three 225G samples.  The sequence of interest, LvivN6, is among the least variant of the 4 fatal cases at the HA amino acid level and shares HA amino acid homology with LvivN2 and TernopilN11.

LvivN6 HA, the "low reactor", is very lightly variant with 1 silent polymorphism common to 3 other Ukraine sequences and 1 amino acid revision, 225G, common to 3 other Ukraine sequences.  LvivN2 HA has accumulated 3 silent polymorphisms, 2 that are not found on other Ukraine sequences, and 1 amino acid revision.  TernopilN10 HA is highly variant with 2 silent polymorphisms and 3 amino acid revisions, 2 that are not found on other Ukraine sequences.  TernopilN11 HA is variant with 3 silent polymorphisms, 1 that is not found on other Ukraine sequences, and 1 amino acid revision.  At the NA, the LvivN6 single SNP impeaches the Neuraminidase segment as an antigen differentiator for this group of sequences due to homology with the remaining three 225G samples. 

In this pandemic era that is unprecedented in most of our lives, science has tools, protocols and reference databases that were not available to the researchers in 1918.   ΣPF11 in these early stages is allowing science a real-time, practically freeze-frame, insight into viral genetic acquisition tracked alongside clinical and bench study data.  The research opportunities to change the direction of this pandemic hang low on the tree, ripe for picking. 

Though we know that outcomes of antisera challenge are not perfectly predictable, a reliable database exists of values from antigenic characterisations including the methods used to attain those values from past seasons of Influenza.  A standing genetic sequence catalog is available from a very large set of individual samples in numerous sub-clades from this reservoir.  While we know that independent labs have reproduced experiments detailing that genetics alone do not entirely correlate with antigen characterisation via antisera cross-reactivity, we also know that aggressively measuring and cross-referencing each minutia in this unprecedented event may crystallise new thinking and build stronger frameworks.

Additional detail such as the list of tested samples and the testing protocols employed will provide necessary background for evaluation.  Were Hemagglutinin (HI) and Neuraminidase (NI) Inhibition studies conducted?  Were both HI and NI observed outcomes ranked as "low reactor" status?  Will the results be reported separately within a reasonable timeframe?  Transparency on the maximum values for "low reactor" ranking, generally between a four-fold to an eight-fold decrease in titers on Hemagglutinin or Neuraminidase Inhibition, will allow a comparison of this vaccine escape event to database entries from past seasons' variation captured for vaccine candidate selection.  Discussion of the actual observed titers that did inhibit, if at all, would perfectly surface the issue.

We would expect a similar finding of "low reactor" on 4 of these sequences if the least variant at NA and HA, LvivN6, showed reduced reaction.  If NIMR has, in fact, officially confirmed this vaccine escape event via the New York Times, their lab books may have notations for 3 other 225G Ukraine sequences in the antisera reactivity panels.

Antigenic diversity, whether due to viral response to human immunity, anti-viral selection pressure or vaccine pressure, is a certainty.  Additional reporting of data that may be on hand would easily clear this issue as to the exact nature of the diversity in circulation today within ΣPF11.

Twenty-six sequences are on record from several temporal and geographic points in the pandemic carrying paired HA and NA cross-segment linkages to these Ukraine fatal cases, including the item, LvivN6, reported and validated as a "low reactor" to the current pandemic vaccine.  Those sequences are seeded throughout major population areas of the world.

Forthright communications on these vaccine escape events is crucial to earning public trust around this ongoing health issue.


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