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Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

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  • Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

    I was reading about the various influenza strains since 1900, and came upon this article about the first cases of re-emerging H1N1 at the Ft. Dix military base in 1976. Read about the testing, especially their results with soldiers who had an H3N2 VAX - cross reactive immunity! (sorry folks, I've been beating this drum for almost a year now).

    http://www.flu.org.cn/en/article-3874.html

    (snip) (A/Mayo Clinic is H1N1)
    Case Finding at Fort Dix

    Case-finding was conducted prospectively and retrospectively (Table). Prospectively, throat washings were collected from patients with febrile, acute respiratory disease who were hospitalized or sought treatment at the emergency room February 1416 (phase I, n = 50) and February 2224 (phase II, n = 45) (7). Attempts were made to obtain paired serum specimens from phase I patients. Specimens were obtained from 60 basic training soldiers, 13 other military personnel, and 22 civilians. A/Victoria/75 (H3N2) virus was isolated from 34 (68%) persons during phase I and 21 (47%) in phase II (7). A/New Jersey/76 (Hsw1N1) was not isolated from any of the 95 patients. One of 34 (3%) persons with an A/Victoria isolate and paired serum samples had a >4-fold rise in titer to A/Mayo Clinic (Hsw1N1) antigen, with an acute titer of <1:10 increasing to 1:20 (7).

    Retrospective study was made possible by an ongoing Adenovirus Surveillance Program, which collected weekly throats swabs and paired serum specimens from a sample (≈3%6%) of basic trainees hospitalized with respiratory disease (7). Specimens had been sent to Army regional laboratories, and 80% of the paired serum specimens from Fort Dix trainees hospitalized between November 1, 1975, and February 14, 1976, went to Fort Meade, Maryland. Serum specimens not depleted by routine studies were stored. Stored serum specimens from 74 Fort Dix trainees were identified at Fort Meade and forwarded to WRAIR; 39 (53%) of the trainees had been hospitalized after January 1, 1976. These serum samples were initially tested against A/Mayo Clinic antigen. Serum samples with >4-fold rises in titer were re-tested against A/New Jersey and A/Victoria/3/75 (H3N2) antigens (7). HAI titers to A/Mayo Clinic and A/New Jersey differed only slightly.

    Concerns that influenza A (H3N2) infection or vaccination might stimulate antibody to A/Mayo Clinic were addressed. Four groups were studied to identify persons with >4-fold heterotypic HAI antibody increases to A/Mayo Clinic. None were found in 39 Fort Dix soldiers who received influenza vaccine in February 1976 (group 1), and none were found among 27 hospitalized soldiers from posts other than Fort Dix who had >4-fold rises in complement fixation (CF) antibody to influenza A (group 2) (7). In the third group, >4-fold rises in antibody titers developed in 3 (8%) of 40 soldiers from Fort Dix and elsewhere who had been hospitalized with an A/Victoria isolate (7). In the fourth group, a single serum sample was studied from each of 168 randomly selected Fort Dix basic trainees who had received their annual influenza vaccination 3 to 4 weeks earlier (11). Only 4 (2%) had HAI titers >1:20 to A/Mayo Clinic (11). In similar studies by others, in 0%6% of persons, heterotypic antibody to influenza A/swine developed after infection with A/Victoria (H3N2) or influenza vaccination (12,13).

    Since heterotypic antibody to A/Mayo Clinic seldom occurred, soldiers who were hospitalized for acute respiratory disease and showed a >4-fold titer rise to influenza A (Hsw1N1) in stored serum specimens from the Adenovirus Surveillance Program were considered to have had A/New Jersey infections. Eight new cases in basic trainees were found. Three (38%) of the 8 solders also had >4-fold antibody rises to A/Victoria. Therefore, 13 male, enlisted soldiers, aged 1721 years, were identified as having had respiratory diseases resulting in hospitalization or death and an A/New Jersey (Hsw1N1) isolate or serologic conversion to A/New Jersey (case-patients). Ten had arrived at Fort Dix between January 5 and February 3, 1976. Three arrived between September 9 and December 30, 1975. Dates of onset of illness were known for 12 and were from January 12 to February 8, 1976. Hospital admissions occurred between January 19 and February 9. Autopsy findings for the only patient who died showed severe edema, hemorrhage, and mononuclear infiltrates in the lungs, consistent with viral pneumonia. No preexisting disease or bacterial infection was found. Four (33%) of the 12 surviving patients had radiologic evidence of pneumonia but their clinical syndromes were similar to those described for patients with infections caused by other influenza A strains (7).

    (snip)
    "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

  • #2
    Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

    So....is this sufficient evidence to consider pre-emptive VAX with a poorly-matched influenza A strain? Just like the HK ducks and their H9N2 recent infection protecting them from H5N1. H3N2 only had two segments from H1N1, yet the recent VAX afforded protection.

    .
    "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


    • #3
      Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

      as I understand protection was poor. Only a few % were protected
      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


      • #4
        Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

        Originally posted by gsgs
        as I understand protection was poor. Only a few % were protected
        If you're referring to the above article, only a few % were even exposed to A/Mayo (H1N1).

        .
        "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


        • #5
          Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

          If we read further in the article (I didn't post it all) we find....

          (snip)
          Summary and Speculation

          A/New Jersey/76 (Hsw1N1) was likely introduced into Fort Dix early in 1976, after the holidays (15). The virus caused disease with radiologic evidence of pneumonia in at least 4 soldiers and 1 death; all of these patients had previously been healthy (7,15). The virus was transmitted to close contacts in the unique basic training environment, with limited transmission outside the basic training group. A/New Jersey probably circulated for a month and disappeared. The source of the virus, the exact time of its introduction into Fort Dix, and factors limiting its spread and duration are unknown (15).

          The Fort Dix outbreak may have been a zoonotic anomaly caused by introduction of an animal virus into a stressed population in close contact in crowded facilities during a cold winter. However, the impact of A/New Jersey virus on this healthy young population was severe in terms of estimated infections, hospitalizations, and duration of the outbreak.

          If the outbreak was more than an anomaly, why did it not extend beyond basic trainees? Several factors merit consideration. Contact between basic trainees and others was limited. Moreover, a swine influenza antigen was included in annual military influenza vaccine formulations from 1955 through 1969 (10). The high antibody titers to A/Mayo Clinic antigen observed with increasing age in the Phlebotomy Clinic population may reflect earlier influenza A (H1N1) infections or vaccine exposure and some protection (11). Also, competition between A/New Jersey and A/Victoria viruses must be considered. The A/Victoria virus spread widely and may have limited the impact of A/New Jersey virus with its lesser ability for human transmission.

          Could the Fort Dix outbreak have resulted from interaction between swine influenza A and A/Victoria viruses? A/Victoria transmission occurred in New Jersey before A/New Jersey was identified at Fort Dix. Is it possible that A/Victoria virus and an early A/New Jersey virus coinfected a soldier with genetic exchange, resulting in a recombinant virus with enhanced human transmission capability? The rapid disappearance of A/New Jersey prohibited studies of virus interactions. Genetic analyses of A/New Jersey, A/Victoria and contemporary A/swine viruses might elucidate a relationship.

          Communication and collaboration existed at the onset of the outbreak and continued throughout the investigation. The points of contact at the NJ Department of Health, Fort Dix, CDC, and WRAIR had been established before the outbreak, so time was not lost identifying organizations and persons who needed to be contacted. Organizational roles were defined early and respected. The development of outbreak investigation plans, collaboration in field and laboratory work, and exchange of information occurred smoothly. An important part of the Army investigation was establishment of points of contact at WRAIR who communicated with military leaders, the NJ Department of Health, CDC, and the press. Military epidemiology and laboratory teams reported to WRAIR points of contact. This system protected these teams from disruptive inquiries.

          The burden on the laboratories supporting this investigation was intense, lasting for weeks. In 1976, WRAIR was a research and field epidemiology laboratory that also operated as a public health reference laboratory. The WRAIR commander had the authority to reallocate and mobilize scientists and laboratory resources. Today, WRAIR no longer functions as a public health laboratory. The depth of resources and flexibility that existed at WRAIR in 1976 cannot be found in other military laboratories (16).
          Duplicating the 1976 laboratory effort today, in timely fashion, would be difficult.

          .
          "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


          • #6
            Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

            another related article at http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

            .
            "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


            • #7
              Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

              Which brings us back to the problem of capacity. What capacity there is was provided to produce seasonal vaccine for the young and old in the industrialised countries that can afford to immunise these populations and there is little spare capacity. To produce meaningful stock piles this production capacity would have to stop producing H1N1 & H3N2 and start H5N1 or at least add it to the cocktail. There is enormous capacity in the non human vaccine capacity and I know it is being looked into but am unclear what the problems in conversion to human capacity are, if anyone knows the answer I would be most grateful if they could post. There seems little commercial incentive to set up lots of additional capacity for pandemic events which will only occur a few times per century. A better option might be to look at an alternative system of cell culture or air lift fermentation monoclonal antibody production who's plant can be usefully redeployed during interpandemic periods.

              Comment


              • #8
                Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                yes, also the effect of H3N2-vaccination is not so big according
                to some statistics. It would be worth a thought to use the
                capacities for H5N1 instead.

                Although, maybe you need a flumist-like vaccination or two shots
                some weeks apart.
                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


                • #9
                  Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                  Originally posted by JJackson
                  ........ To produce meaningful stock piles this production capacity would have to stop producing H1N1 & H3N2 and start H5N1 or at least add it to the cocktail. There is enormous capacity in the non human vaccine capacity and I know it is being looked into but am unclear what the problems in conversion to human capacity are, if anyone knows the answer I would be most grateful if they could post. There seems little commercial incentive to set up lots of additional capacity for pandemic events which will only occur a few times per century. A better option might be to look at an alternative system of cell culture or air lift fermentation monoclonal antibody production who's plant can be usefully redeployed during interpandemic periods.
                  Capacity...that sticking point. If we take "commerical" out of the equation, we'd be ahead.

                  If we build capacity for public safety with regard to defense, why not disease? I remember all the bomb shelters stocked with food during the 50s....& how many times has the US used them in the last century?

                  Think of all the other things that are produced in the name of public safety, from excess packaging to air bags. We're already paying a price every day for our "safety" - so why not safety from disease?

                  ?Mingus had posted some info about using animal VAX factories for reserve capacity.

                  .
                  "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


                  • #10
                    Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                    Originally posted by gsgs
                    .....worth a thought to use the
                    capacities for H5N1 instead.

                    Although, maybe you need a flumist-like vaccination or two shots
                    some weeks apart.
                    Since it worked for ducks (& appaarently some soldiers), well.....I'd say let's do like the ducks.

                    .
                    "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


                    • #11
                      Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                      Originally posted by AlaskaDenise
                      If we build capacity for public safety with regard to defense, why not disease?
                      .
                      Like you I would argue this is not a commercial but a national defense imperative. We spend obscene amounts of money on military defense when there are no credible threats to justify it, here we have a know enemy that regularly kills far more of our populace than other nation states but we do not spend 1% of the military budget combating it.

                      Comment


                      • #12
                        Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                        Wudda been a no-brainer for Rumsfeld to get involved with--seeing he is on board of directors for Tamiflu production....

                        Comment


                        • #13
                          Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                          is the duck vaccine a live, attenutated vaccine; or a killed vaccine? Just curious.
                          Upon this gifted age, in its dark hour,
                          Rains from the sky a meteoric shower
                          Of facts....They lie unquestioned, uncombined.
                          Wisdom enough to leech us of our ill
                          Is daily spun, but there exists no loom
                          To weave it into fabric..
                          Edna St. Vincent Millay "Huntsman, What Quarry"
                          All my posts to this forum are for fair use and educational purposes only.

                          Comment


                          • #14
                            Re: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                            Originally posted by LMonty
                            is the duck vaccine a live, attenutated vaccine; or a killed vaccine? Just curious.
                            The ducks I referred to caught a natural case of H9N2, which gave them immunity to H5N1 - only for about 100 days. I found another similar case with geese & chickens at http://www.pubmedcentral.nih.gov/art...i?artid=136145

                            Protective Cross-Reactive Cellular Immunity to Lethal A/Goose/Guangdong/1/96-Like H5N1 Influenza Virus Is Correlated with the Proportion of Pulmonary CD8<SUP>+</SUP> T Cells Expressing Gamma
                            Interferon

                            (snip)
                            Here we show that the currently circulating H9N2 influenza viruses provide chickens with cross-reactive protective immunity against the currently circulating H5N1 influenza viruses and that this protective immunity is closely related to the percentage of pulmonary CD8<SUP>+</SUP> T cells expressing gamma interferon (IFN-γ). In vivo depletion of T-cell subsets showed that the cross-reactive immunity was mediated by T cells bearing CD8<SUP>+</SUP> and T-cell receptor (TCR) α/β and that the Vβ1 subset of TCR α/β T cells had a dominant role in protective immunity.
                            .
                            .
                            .
                            In conclusion, our findings demonstrate that memory CD8<SUP>+</SUP> T cells and TCR α/β T cells primed by exposure to H9N2 influenza virus are key elements in cross-reactive immune control of the highly pathogenic H5N1 influenza virus in chickens and that protective immunity is correlated with the percentage of memory CD8<SUP>+</SUP> T cells expressing IFN-γ in the lungs.

                            .
                            "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: Cross-reactive immunity with H1N1 in 1976 Ft. Dix infections?

                              so, this was no vaccine for the ducks, but a real infection.
                              Doing the same with a vaccine could be more difficult
                              and the "normal" way with the seasonal flu-vaccine might not be enough.

                              Also, I read that this T-cell immunity is worse in humans than
                              in mice (and ducks ?)

                              It seems to work with natural infection and that's how it is explained
                              why a pandemic almost wipes out the previous strains.

                              See e.g. the Ferguson,Bush paper
                              http://cmbi.bjmu.edu.cn/news/report/2005/flu/106.pdf
                              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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