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One of the D225G cases is a low reactor?

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  • One of the D225G cases is a low reactor?

    The presence of D222G or its absence seems to be immaterial outside Ukraine, as - for example - Italy experienced a sudden increase in fatalities due H1N1 2009.

    The direct link between D222G and higher case- fatality rate is at least unproven.

    As usual, host conditions, delayed treatment of cases, underlying conditions continue to remain totally overlooked.

    Some people are crying wolf for a decade at least.

    Every time, a mutation is responsible for a higher mortality than previously recognized; but - so far - all these theories remained unproven.

    We should focus on the best way to cure these patients, with timely treatment with antivirals and other life-saving procedures, including prompt establishing of respiratory assistance.

    Vaccines are a tool in these circumstance at least until it is definitely concluded that they are not longer effective.

  • #2
    Re: One of the D225G cases is a low reactor?

    That is a good point. No one is arguing that the virus mutated in Ukraine; in fact, as more samples test positive worldwide, we are finding more D225G, even before the Ukraine outbreak, which rules out a mutation in Ukraine.

    So whatever is going on with regard to D225G and severe illness (and I still don't think we even begin to understand that) was going on long before H1N1 got to Ukraine. To me, at least, Ukraine and D225G are two separate issues. The first is solved, IMO, by the diagnosis of Pandemic H1N1 and the lack of any specific mutation IN Ukraine (as opposed to global D225G). The second is a total mystery which we seem to barely have the tools to even approach.

    And as far as crying wolf for a decade, I am certainly well aware of that. That is part of the reason I am still stunned by the way the pandemic developed in April. There wasn't anyone there to cry wolf, even though the wolf was biting people...

    Comment


    • #3
      Re: One of the D225G cases is a low reactor?

      I agree with IOH - even a low immunogencity from vaccination is better than none until a well matched vaccine is available

      Comment


      • #4
        Re: One of the D225G cases is a low reactor?

        Originally posted by alert
        The recent upgrade of the characterization sheet for A/Lviv/N6/2009 to "low reactor" status has created significant pandemic concern.
        I do not know where to find the original information and if the same is true for other viruses with the same mutation, but if true this could mean that the virus with this mutation, regardless of the fact if it causes more severe disease or not, is not recognized well by people who have been vaccinated with the H1N1 vaccine. That would mean that vaccinated people would be susceptible to this version of the virus. If the mutation also confers a more severe disease it is bad news. But the facts are not clear yet as far as I can see.

        Comment


        • #5
          Re: One of the D225G cases is a low reactor?

          what means "low reactor" ?
          I'm interested in expert panflu damage estimates
          my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

          Comment


          • #6
            Re: One of the D225G cases is a low reactor?

            Originally posted by Vibrant62 View Post
            I agree with IOH - even a low immunogencity from vaccination is better than none until a well matched vaccine is available
            I agree too.
            "May the long time sun
            Shine upon you,
            All love surround you,
            And the pure light within you
            Guide your way on."

            "Where your talents and the needs of the world cross, lies your calling."
            Aristotle

            “In a gentle way, you can shake the world.”
            Mohandas Gandhi

            Be the light that is within.

            Comment


            • #7
              Re: One of the D225G cases is a low reactor?

              if increased virulence is linked to one special substrain,
              D225G or not, that is surely worth watching.

              Will that strain spread to other countries and cause severe disease ?
              Will it crowd out the other strains ?
              I'm interested in expert panflu damage estimates
              my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

              Comment


              • #8
                Re: One of the D225G cases is a low reactor?

                Originally posted by gsgs View Post
                what means "low reactor" ?
                That antibodies raised against the vaccine strain react only weakly to this strain

                Comment


                • #9
                  Re: One of the D225G cases is a low reactor?

                  hmm, 225D is in one of the major epitopes(which) and 225G
                  avoids that epitope ?!


                  ******: ...IRPKVRDQEGRM...
                  seasonal: ...KRPKVRDQEGRI...


                  RPKVRDQEGRI,>A/Kansas/UR06-0068/2007(H1N1)
                  RPKVRGQAGRI,>A/Index/1977(H1N1)
                  RPKVRDQSGRM,>A/Denver/1957(H1N1)
                  RPKVRDQAGRM,>A/Index/early human
                  RPKVRDQAGRM,>A/Brevig Mission/1/1918(H1N1)
                  RPKVRGQAGRM,>A/Index/early swine
                  RPKVRGQAGRM,>A/swine/Jamesburg/1942(H1N1)
                  RPKVRGQAGRM,>A/New Jersey/1976(H1N1)
                  RPKVRDQEGRM,>A/******/index/2009/02/01
                  RPKVRGQEGRI,>A/Taiwan/01/1986///
                  RPKVRGQEGRI,>A/Beijing/262/1995///
                  RPKVRDQEGRI,>A/New Caledonia/20/1999///
                  RPKVRDQEGRI,>A/Solomon Islands/3/2006/08/21/
                  RPKVRDQEGRI,>A/Brisbane/59/2007/07/01/
                  RPKVREQAGRM,>A/swine/Germany/2/1981(H1N1)=1578
                  RPKVRDQAGR-,>A/******-match/1-2/07(H3N2)
                  RPKVRDQPGRM,>A/UK/1/1933(H1N1)
                  RPKVRDQAGRM,>A/Puerto Rico/8-1/1934(H1N1)
                  RPKVRGQEGRI,>A/Texas/36/1991(H1N1)
                  RPKVRNQEGRI,>A/Chile/1/1983(H1N1)

                  epitope at IEDB : RPKVRDQEGRIN
                  I'm interested in expert panflu damage estimates
                  my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                  Comment


                  • #10
                    Re: One of the D225G cases is a low reactor?

                    It is noted on the records that none of the 4 received treatment. If they had been treated in a timely manner, they might have had different outcomes.
                    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

                    Comment


                    • #11
                      Re: One of the D225G cases is a low reactor?

                      Originally posted by gsgs View Post
                      hmm, 225D is in one of the major epitopes(which) and 225G
                      avoids that epitope ?!


                      ******: ...IRPKVRDQEGRM...
                      seasonal: ...KRPKVRDQEGRI...

                      As postion 225 is in the binding site of the haemagglutinin (that binds to respiratory epithelium) antibodies that recognize this site can prevent the binding of the virus to the cells, and thus block infection. If there is a different amino acid in this position, blocking antibodies induced against the vaccine strain may not bind efficiently to the new variant anymore, meaning that the vaccine is not effective anymore. I am not saying this is the case here, but this is the explanation of what could happen.

                      Comment


                      • #12
                        Re: One of the D225G cases is a low reactor?

                        Originally posted by Toaster2 View Post
                        As postion 225 is in the binding site of the haemagglutinin (that binds to respiratory epithelium) antibodies that recognize this site can prevent the binding of the virus to the cells, and thus block infection. If there is a different amino acid in this position, blocking antibodies induced against the vaccine strain may not bind efficiently to the new variant anymore, meaning that the vaccine is not effective anymore. I am not saying this is the case here, but this is the explanation of what could happen.
                        That would also explain why 225G (being the concensus value in the 1940-1956) wasn't a problem if the 1940-1956 vaccine contained a "G".

                        I'd like to find the exact sequences of those early vaccines and see what was at HA/225.

                        .
                        "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

                        Comment


                        • #13
                          Re: One of the D225G cases is a low reactor?

                          Originally posted by AlaskaDenise View Post
                          That would also explain why 225G (being the concensus value in the 1940-1956) wasn't a problem if the 1940-1956 vaccine contained a "G".

                          I'd like to find the exact sequences of those early vaccines and see what was at HA/225.

                          .
                          Could be interesting. But please don't forget that antibodies recognize discontinuous epitopes, meaning that not only position 225 but also adjoining or even distant amino acids determine binding of blocking antibodies. So the context of 225G is as important as 225G itself.

                          Comment


                          • #14
                            Re: One of the D225G cases is a low reactor?

                            Originally posted by Toaster2 View Post
                            Could be interesting. But please don't forget that antibodies recognize discontinuous epitopes, meaning that not only position 225 but also adjoining or even distant amino acids determine binding of blocking antibodies. So the context of 225G is as important as 225G itself.
                            Yes.

                            Mamabird pointed me to an excellent H1N1 epitope paper at:

                            http://iedb.zendesk.com/forums/45499/entries/35037



                            What epitopes does the human immune system recognize in swine flu?

                            This forum post contains a summary of our analysis of swine flu epitopes.The definite version (2.0) has been published in PNAS as an open access article, and is attached to this post here. Previous versions are attached to this post as well. The dataset is included as supplemental material on the PNAS website.

                            Abstract

                            A major concern about the ongoing swine-origin H1N1 influenza virus (S-OIV) outbreak is that the virus may be so different from seasonal H1N1 that little immune protection exists in the human population. In this study, we examined the molecular basis for pre-existing immunity against S-OIV, namely the recognition of viral immune epitopes by T cells or B cells/antibodies that have been previously primed by circulating influenza strains. Using data from the Immune Epitope Database, we found that only 31% (8/26) of B cell epitopes present in recently circulating H1N1 strains are conserved in the S-OIV, with only 17% (1/6) conserved in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In contrast, 69% (54/78) of the epitopes recognized by CD8+ T cells are completely invariant. We further demonstrate experimentally that some memory T cell immunity against S-OIV is present in the adult population and that such memory is of similar magnitude as the pre-existing memory against seasonal H1N1 influenza. Since protection from infection is antibody-mediated, a new vaccine based on the specific S-OIV HA and NA proteins is likely to be required to prevent infection. However, T cells are known to blunt disease severity. Therefore, the conservation of a large fraction of T cell epitopes suggests that the severity of an S-OIV infection, as far as it is determined by susceptibility of the virus to immune attack, would not differ much from seasonal flu. These results are consistent with reports about disease incidence, severity and mortality rates associated with human S-OIV.
                            (good links provided in article)

                            .
                            "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

                            Comment


                            • #15
                              Re: One of the D225G cases is a low reactor?

                              discontinuous epitopes ?
                              I didn't know that. Referrence ?
                              I'm interested in expert panflu damage estimates
                              my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                              Comment

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