A $707 million investment in cell-based influenza vaccine

16 December 2011

novartis-holly-springs-usThe United States has provided a large sum of money to pharmaceutical giant Novartis to produce influenza vaccines grown in cell culture. According to CIDRAP:

Novartis’s US efforts have been spurred by two major federal contracts. In 2006 the firm won a $220 million HHS contract to develop cell-based flu vaccines, and in January 2009 HHS awarded a $487 million contract to help build the Holly Springs facility.

The facility consists of six connected buildings with 430,000 square feet of manufacturing, laboratory, and office space on a 167-acre site, Novartis reported in a news release. The company has about 400 employees there now and plans to expand to 500 by the end of 2012. Power said the facility is expected to be ready for full-scale commercial production in 2013.

Is this a good investment of US science dollars? Consider the following points:

  • A cell-based vaccine is expected to shorten by a few weeks the time required to produce a vaccine for a new influenza virus strain
  • No cell-based influenza vaccine is currently licensed for use in the US
  • Cell-based influenza vaccines use the same technology developed 50 years ago for egg-grown vaccine, with the exception that the virus is propagated in a different host
  • Inactivated influenza vaccine is not very good – it is 59% effective in individuals 18-65 years of age

We need a completely different influenza virus vaccine, not a retread of the existing process. Promising new approaches include virus-like particle vaccines produced in plants that can be made cheaply, rapidly, and appear to be immunogenic and safe in humans. Influenza vaccines that can protect against all viral strains now seem possible, and these vaccines will probably not be based on growing influenza viruses in eggs or cell culture.

I suspect that contemporary influenza vaccines produced in eggs or cell culture will be replaced with new vaccines within the next decade. With all this in mind, does it make sense to invest $707 million in a vaccine that has such a short life span? Even more money is at stake – according to CIDRAP, “Novartis is one of five companies that received sizable HHS contracts in 2006 to develop cell-based vaccines.” The new Novartis plant will not be able to supply all the influenza vaccine required by the US (and having a sole supplier is not a good idea). Are there enough individuals with severe egg allergies to justify this investment? Or is this a project that seemed like a good idea in 2006 but is now an anachronism?

  • Dr. Jordan

    And of course let the autoimmune disease begin! This cell base is using man’s best friend, yep DOG KIDNEY CELLS. I wonder how long it will be before viruses from the dog come across into those vaccines, can anyone say RABIES, or DISTEMPER or perhaps HERPES????

  • Max

    It is surprising to me that VLP technology of Novavax does not get more attention.
    Why does bigger always seem to be better Novartis vs Novavax ?

  • Adam Abdulhafid

    The two contracts add up to be $707 millionn dollars. What happened to the other $100 million dollars that it isn’t counted as part of the vaccine investment?

  • http://www.virology.ws profvrr

    My error – thanks for pointing it out. Fixed.

  • gsgs

    we discussed this in length in 2006, when Bush decided to spend $7B over
    the next 3 yearson pandemic preparation, most of which went into vaccines
    and antivirals.USA was dependent on other countries wrt. quick mass
    production of flu-vaccines and world capacity was too low in case of a
    pandemic.Cell-based vax has several advantages over egg-based. How much can
    be produced in -say- 1 year ?Again this was discussed in 2006 and I
    don’t see why it should no longer be valid.It did work in Marburg 2009,
    although egg-based vax was more competitiveand demand was not so high after
    it turned out that the pandemic was mild.It is not clear yet whether we
    will have universal flu-vax and when and how wellit protects against special
    pandemic strains as compared to conventionalstrain-specific vax, I’d assume
    it’s less efficient here. Well, you couldgive both, they target different
    parts of the virus.http://en.wikipedia.org/wiki/Influenza_research.
    In the event of a flu pandemic, the facility is designed to have the capacity to
    make up to 150 million monovalent (single strain) doses each year within 6
    months of a pandemic declaration, Novartis saidin May 2007, WHO said
    that a universal flu vaccine may be more than a decade away. world
    flu-vaccine capacity could “nearly double” by 2009 to 700 million doses of
    seasonal vaccine.

    (or 2.1B of monovalent vaccine, 2 doses needed)

    In the next 3 to 5 years … 3 billion doses per year.

     

    how well would mass-vaccination protect ?

    For Ohio a study estimated that 300000 Mexflu cases were prevented
    with

    4M shipped doses. 13 doses per one prevented case.

    In a H5N1 pandemic however it could become a decicive measure -together
    with others-

     to get R0 below 1 and stop a wave.

    The biggest expected role with H5N1 would be not to prevent cases, but to
    reduce severety

    and mortality.

    How likely is a severe H5N1 pandemic ? I tried to figure out what experts
    think …

    my last estimate was ~5% per year, I haven’t yet thought about how much
    the

    “ferreting” increases it … But even with 1% the $700M would be
    justified

  • Jack

    Hi Professor,

    This story came up the other day from the BBC in the UK about ‘Draco’ an antiviral they are looking at: http://www.bbc.co.uk/news/magazine-16165605

    Could such a broad-based antiviral really hope to ‘obliterate the threat of a global pandemic and mitigate health scares
    such as that caused by the Sars virus in 2002 or bird flu in 2009′?

    I mean is it only theoretically possible? Haven’t scientists been searching for a cure for the ‘common cold’ for aeons? I thought such a thing impossible.

  • Arthur

    Egg-based vaccine production may be difficult with the somewhat
    predictable seasonal influenza, and even more with an unpredictable
    pandemic strain. Eggs must be available in huge quantities and a disruption in
    egg supply, for any reason (for example, a disease affecting chickens) may
    hamper vaccine production. Moreover, some influenza strains grow slowly in eggs
    (it has already happened, in recent years), which can result in severe
    delays in vaccine production. Finally, some influenza viruses, because of their
    avian origin, may be pathogenic for eggs and as a result, the vaccine could not
    be produced.

    Universal influenza vaccines or Virus-Like Particle vaccines are
    welcome, but it may take several years before these new vaccines are available;
    don’t you think that in the meantime cell based vaccines could be a resource
    against the emergence of a new pandemic strain (e.g.,
    H5N1)?

  • http://www.virology.ws profvrr

    We discussed DRACO in TWiV 146: Draco’s potion. It’s not likely to be useful as a broad spectrum antiviral, in part because it is a large protein that would induce an immune response. It’s a good proof of concept for building a multi-modular antiviral, but not ready for the market by any means.

  • http://www.virology.ws profvrr

    I acknowledge the shortcomings of egg-based vaccine production, but all the problems you cite can be overcome (e.g. avian viruses killing the eggs – solved by replacing all but the viral glycoprotein genes with those from a human strain). Furthermore, there are problems with cell-based vaccine production – it’s not easy to make 100,000 liter batches in cells and my understanding from the European experience is that there are frequent failures. If we are worried about H5N1 we should be stockpiling egg-based vaccine.

  • Jack

    Thanks. I shall have a listen.

  • Arthur

    Thank you, your answer is very clear. The research is taking on new roads, like the one shown in your post of October 13, 2010. In addition, a study recently published on PlosOne seems rather intriguing: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028001 

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