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CIDRAP >> Firm says 'universal' flu vaccine passed early test

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  • CIDRAP >> Firm says 'universal' flu vaccine passed early test

    CIDRAP >> Firm says 'universal' flu vaccine passed early test
    Firm says 'universal' flu vaccine passed early test

    Robert Roos * News Editor
    Nov 11, 2008 (CIDRAP News) –

    A vaccine designed to offer protection against many strains of influenza viruses appeared safe in low doses and triggered a satisfactory immune response in a phase 1 clinical trial, the vaccine's developer announced recently.


    The vaccine, made by VaxInnate Inc., Cranbury, N.J., targets the M2 protein of influenza A viruses, a surface protein that differs little among different strains of type A.

    Existing flu vaccines target hemagglutinin (HA), a flu surface protein that often mutates, making it necessary to change the vaccine each year to cover the predominant strains in circulation.

    A vaccine targeting a protein found in all or most flu strains could reduce or eliminate the need to change the vaccine each year.

    The company reported the results in an Oct 26 press release and at the Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Diseases Society of America (ICAAC/IDSA) meeting, held Oct 24-28 in Washington, DC.

    "VaxInnate's M2e universal flu vaccine candidate has passed a critical initial test," David Taylor, MD, the company's chief medical officer, said in the news release. "We're encouraged by these data, which demonstrate that the vaccine is safe and elicits potent immune responses at doses below a microgram [mcg] of vaccine antigen, and does so without the use of conventional adjuvants."

    Fewest events at lowest doses
    The phase 1 trial was a double-blind study designed to test the safety and immunogenicity of four different doses of the vaccine: 0.3, 1, 3, and 10 mcg. It was conducted in Galveston, Tex., and Lenexa, Kan.In the trial, 60 healthy volunteers between the ages of 18 and 49 received one of the four doses or a placebo in two injections 28 days apart, the company reported. Safety was assessed 1 and 7 days after immunization, and immune response was examined 7, 14, and 28 days after each dose.

    Seroconversion was defined as a serum IgG and anti-M2e antibody value of at least 0.174 mcg per milliliter and a fourfold increase in antibody titer.

    The two lowest doses were safe and well-tolerated in all the volunteers; they yielded an immune response in 18 of 24 volunteers after the first dose and in 23 of 24 after two doses, VaxInnate said.

    However, the two highest doses "were associated with the presence of flu-like symptoms in some of the subjects."

    "Given the strength of the antibody responses and the absence of significant adverse reactions at the two lowest doses (0.3 and 1.0 mcg), VaxInnate intends to continue development and clinical evaluation of the vaccine candidate at doses of 1.0 mcg and less," the company said.

    Christine Turley, MD, primary investigator in the study, said in the release that the results for the two lowest doses "suggest that the M2e vaccine candidate could be a promising and much-needed new option for prevention or attenuation of influenza A disease."

    She is director of clinical trials and clinical research in the Sealy Center for Vaccine Development, University of Texas Medical Branch (UTMB), Galveston.

    The vaccine consists of the ectodomain of the M2 protein, fused to flagellin, a bacterial protein. The company uses recombinant bacteria to produce the vaccine, a technique that the company says is faster than conventional egg-based production or cell-culture production.

    Flagellin interacts with the immune system's toll-like receptors, which serve in human immune cells as sentries to detect pathogens and mount a general defense, according to VaxInnate.

    This initial defense stimulates an adaptive immune response that includes production of pathogen-specific antibodies, the company said.

    'Encouraging but not definitive'
    Dr. Kristin Nichol, an experienced flu immunization researcher who was not involved with the study, described VaxInnate's results as promising but advised a wait-and-see attitude. She is associate chief of staff for research at the Minneapolis VA Medical Center.

    "The notion of a universal influenza vaccine or any kind of influenza vaccine that reduces the need for annual vaccination or provides better or more reliable protection against influenza viruses—that will be very useful to us," she said. "Until a vaccine goes all the way through phase 3 clinical trials and we have good evidence about actual protection, the verdict is out. But certainly there are a number of kinds of vaccines in development, such as this one, that are exciting with regard to the prospect of a more universal kind of vaccine."

    Nichol said the measures of immune response used by VaxInnate are reasonable and generally correlate with actual protection, but do not guarantee it. "It's encouraging but not definitive until we see the clinical protection data," she said.

    Plans for targeting type B
    The M2e vaccine targets influenza A but not influenza B, the other major type. Type A viruses generally cause more severe illness than type B. Seasonal flu vaccines normally target two type A subtypes—H1N1 and H3N2—and one type B strain, all of which typically circulate each season.

    While acknowledging that the M2e vaccine would not cover type B viruses, VaxInnate's Taylor told CIDRAP News that the company also hopes to develop a second-generation universal vaccine that would target both A and B.

    Meanwhile, he suggested possible uses for the M2e vaccine by itself, assuming it is successful.

    "Should M2e be shown to be protective for influenza A, it’s possible that other universal antigens could be developed for influenza B," Taylor said in an e-mailed statement. "In the developing world, where influenza vaccine is not available, M2e could be a cost-effective way to provide influenza A coverage."

    VaxInnate is working to develop a second-generation universal vaccine that has M2e and another conserved antigen that will address influenza B strains, as well as influenza A strains.

    Efficacious universal vaccines for influenza that cover both A and B strains could potentially replace the more standard HA vaccine in some markets and market segments, even in the developed world."

    Taylor also said that in countries where conventional seasonal flu vaccines are available, the M2e vaccine could be used in combination with them to provide increased protection in case the strains in the seasonal vaccine don't match well with circulating strains.

    He also commented that VaxInnate is developing seasonal flu vaccines in which its recombinant-bacteria technology is used to make both the A and B components. A vaccine targeting a Solomon Islands strain of H1N1 is currently in clinical testing, and a type B vaccine may become available next year, he said.

    The Bill and Melinda Gates Foundation supported the M2e vaccine trial with a $9.5 million grant to UTMB to improve control of flu in the developing world, the company said.

    See also:
    Oct 26 VaxInnate press release http://www.marketwatch.com/news/stor...1%7D&dist=hppr
    -
    <cite cite="http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/nov1108flushot.html">CIDRAP >> Firm says 'universal' flu vaccine passed early test</cite>

  • #2
    Re: CIDRAP &gt;&gt; Firm says 'universal' flu vaccine passed early test

    my summary:

    phase 1 out of 3 required phases completed for universal flu-vaccine

    60 received one of the four doses or a placebo in two injections 28 days apart

    Seroconversion was defined as a serum IgG and anti-M2e antibody value of at least 0.174 mcg per milliliter and a fourfold increase in antibody titer.

    doses of 0.3 and 1 mcg yielded an immune response (="seroconvertion" ?)
    in 18 of 24 volunteers after the first dose and in 23 of 24 after two doses

    However, the two highest doses "were associated with the presence of flu-like symptoms in some of the subjects."
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

    Comment


    • #3
      Re: CIDRAP &gt;&gt; Firm says 'universal' flu vaccine passed early test

      snips from a recent article:

      VaxInnate takes flu virus protein antigens--the basic building block in existing vaccines--and combines them with the bacterial protein flagellin, which interacts with toll-like receptors, heightening the potency of the vaccine. In essence they're the body's policeman and garbage man, explains VaxInnate CEO Alan Shaw, PhD. They pick up pathogens and then chew them up. And by producing the fusion flagellin-antigen in bacteria, they can brew up vast stockpiles in weeks at a significantly reduced cost.

      "For the universal vaccine we have a study to show efficacy," says Shaw. "We'll have data at the end of spring next year," he says. A number of studies are being done on a seasonal flu vaccine. "We're looking to go into the elderly next," he says, a group that has the highest risk of death from seasonal flu and the lowest response rate to existing vaccines.

      Says Shaw: "We'll have that data toward the end of the year."

      VaxInnate's platform technology can be pointed in a variety of directions, including dengue fever. And other developers have expressed an interest in licensing the technology for targets that VaxInnate doesn't have the time or resources to aim at.

      "We're 52 people," explains Shaw. "We have to focus on a few things we can accomplish. We can't do everything all at once."

      Swine flu, though, proved too compelling to overlook. VaxInnate launched a special program for the new flu soon after the virus appeared in Mexico.

      But while the developer is making progress in its field, the CEO sees a long road ahead before the company can reach an approval for seasonal flu. That's a goal VaxInnate likely won't reach on its own until 2014.

      But Shaw isn't discouraged or surprised.

      Theoretically, though, a pandemic could change that timeline dramatically.

      "The FDA has a guidance on producing pandemic vaccines," says Shaw. "We are working on a swine flu prototype right now. We're on our way. We can have a clean protein to put in animals six weeks from the start of the exercise. And then we'll see what goes on and decide what to do next. The point is you can turn these around quickly."

      VaxInnate believes that it can use its approach to produce two billion doses over a very short period. E coli doubles quickly, says the CEO. The flagellin technology makes it potent. And the production can be done by existing contractors. You don't need to build a special facility to start supplying vaccine.

      If they can make their case, VaxInnate might overtake the cell-based approach to vaccine production before it becomes established as the primary successor to egg-based work.

      "I wouldn't be surprised," says Shaw. "If you look at the economics of cell-based production, it doesn't really make commercial sense to a lot of people."

      http://www.fiercebiotech.com/special...oper-vaxinnate
      The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

      Comment


      • #4
        Re: CIDRAP &gt;&gt; Firm says 'universal' flu vaccine passed early test

        Universal influenza A vaccine: Optimization of M2-based constructs

        Virology
        Volume 337, Issue 1, 20 June 2005, Pages 149-161

        Marina De Filettea, Willy Min Joua, Ashley Birkettb, Katie Lyonsb, Brian Schultzb, Anne Tonkyrob, Stephanie Reschb and Walter Fiersa, ,

        aDMBR, Ghent University-VIB, FSVM-building, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium


        Received 5 January 2005; revised 1 February 2005; accepted 1 April 2005. Available online 3 May 2005.

        Abstract

        M2e is the external domain of the influenza A M2-protein. It is minimally immunogenic during infection and conventional vaccination, which explains in part its striking sequence conservation across all human influenza A strains.

        Previous research has shown that when M2e is linked to an appropriate carrier such as hepatitis B virus core (HBc) particles, it becomes highly immunogenic, eliciting antibodies that fully protect mice against a potentially lethal virus infection. Different M2e-HBc particles and adjuvants suitable for human use were compared for induction of protective immunity. Strong immunogenicity and full protection were obtained after either intraperitoneal or intranasal administration. The most protective particle contained three consecutive M2e-copies linked to the N-terminus of HBc. Although HBc is highly immunogenic, the optimized M2e-HBc vaccine induced an anti-M2e antibody titer even higher than that of anti-HBc.

        Keywords: Influenza A; M2-protein; Hepatitis B virus; HBV core; M2e-HBc

        Article Outline

        http://www.sciencedirect.com/science...15ddbd47f8d49a
        "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: CIDRAP &gt;&gt; Firm says 'universal' flu vaccine passed early test

          The M2 segment is NOT identical between strains or within a strain.

          I searched for M2-human-all strains and picked 2 of each strain.

          So, is it targeting the function of the entire segment, or a conserved portion of the segment?

          .
          "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: CIDRAP &gt;&gt; Firm says 'universal' flu vaccine passed early test

            #3: ""For the universal vaccine we have a study to show efficacy," says Shaw. "We'll have data at the end of spring next year," he says."

            Bye, bye fastness ...

            Comment

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