GlaxoSmithKline (GSK) has shed some light on the H1N1 vaccine production arena, announcing that they have received orders from governments aiming to stockpile a new candidate H1N1 vaccine. The announcement provides several data points on plans for the vaccine.
GSK expects the first doses of the vaccine to be available 4-6 months after receiving the virus seed from the WHO. I think the virus seed could be ready as early as June, putting vaccine availability in the Q4 2009 timeframe. They have noted that they plan to complete the 2009/2010 seasonal influenza vaccine campaign by the end of July. This is consistent with the proposed timeline for H1N1 vaccine production, allowing it to begin in August.
Of course all of this is subject to regulatory approval. However the pandemic vaccine will be produced by a similar process to the seasonal vaccine and in the same facilities, so it seems improbable that there would be any significant regulatory delays. GSK already received a European license for a pandemic vaccine based on a ‘mock-up’ dossier, and expects this to facilitate a faster registration of the new A (H1N1) vaccine. This is currently being discussed with EU regulatory authorities.
A notable aspect of the GSK pandemic vaccine is the proposed inclusion of GSK’s proprietary ASO3 adjuvant. ASO3 is an alpha-tocopherol based oil-in-water emulsion, similar to Novartis’s MF59. Adjuvants typically stimulate immune responses to the antigen components of the vaccine, and can generate a higher immune response with lower amounts of antigen when compared to the unadjuvanted formulation. This effect can decrease the amount of antigen required in a dose and hence increase the number of vaccine doses that can be produced. In addition an adjuvanted flu vaccine has the potential to provide protection even if the strain drifts, a distinct possibility with the current H1N1.
This is of such interest because, to the best of my knowledge, no non-alum adjuvanted vaccine has been approved by the US FDA. A recent NIAID/NIH sponsored workshop was held to discuss adjuvants, including their inclusion in pandemic flu vaccines. The emergence of H1N1 could accelerate the resolution of the adjuvant debate as the US Department of Health & Human Services grapples with the potential public health emergency.
The seasonal influenza vaccine contains a 15mcg dose of each of three antigens, and no adjuvant. If prepared as a pandemic vaccine, the H1N1 vaccine will contain only the single antigen. It is unknown at this time how much unadjuvanted antigen will have to be included in the vaccine formulation to elicit seroprotection, but for the H5N1 vaccine as much as 90mcg per dose has been required. The adjuvanted dose could be as low as 3-10mcg, realising a significant increase in the available doses. The H5N1 pandemic vaccine requires two doses to seroprotect, so it is also possible that the H1N1 vaccine will be similar, requiring 2 doses. This will place additional strain on the available manufacturing capacity. An adjuvant may become mandatory for translating the available manufacturing capacity into sufficient doses to meet global demand, and GSK clearly intend on travelling down that pathway. It will be fascinating to see how FDA reacts.
Tags: adjuvant, flu, H1N1, Manufacturing, swine flu, Vaccine
Do you have any more insight into why FDA has not approved non-alum-based vaccines? Any info or links would be appreciated.
[...] on schedule, then August may mark the first use of the H1N1 vaccine and immunisation with the first commercial dose of the AS03 [...]
ADJUVANT – VACCINE booster or “nano-bomb”???
They were intent on creating something Mother Nature had not. “Designer disease,” they would later call it.
Dr. Sergei Popov was one of the Soviet Union’s best germ warriors, and running highly classified field research projects at The State Research Center of Applied Microbiology at Obolensk, and another laboratory in Siberia, specializing in viruses called VECTOR. While at Obolensk, Popov supervised a program codenamed “FACTOR”—as in “pathogenic factors” or “virulence factors”—where he helped engineer designer germs resistant to antibiotics. That is when he got interested in U.S. research with myelin basic protein.
American molecular biologist had mapped out the entire amino acid sequence for myelin—one of the chief components of the insulation surrounding nerve endings. Now they were hard at work trying to identify the epitopes on viruses that would cross-react with a special site on the myelin molecule to which an antibody might react and, cause experimental allergic encephalomyelitis—the animal version of multiple sclerosis. As the California-based scientists Robert Fujinami and Michael Oldstone explained in a landmark paper in Science: “during the cross-reacting immune response, virus may be cleared, but the components of the immune attack continues to assault self elements. The autoimmune response leads to tissue injury that, in turn, releases more self antigen, and the cycle continues.” Fujinami and Oldstone called the initial infection a “hit and run event.” By this they meant the virus attacked, and though it didn’t stick around, it left behind lasting damage. That is because the immune system continues to attack the molecule in the body that resembles the one in the germ, long after the immune system has gotten rid of the germ. Once this self-destructive process begins, it never stops; our bodies continue making the molecule the immune system is now trained to attack. If this new target for the immune system happened to be myelin, for example, the body would continue making this protein in order to replenish and repair the sheath around it’s nerve endings. But in the act of doing so, the body immunizes itself against itself, administering over and over again what amounts to a booster dose of something that the immune system now wants to get rid of. This vital constituent of your own body is now the enemy, and the immune system is now programmed to obliterate it in an endless loop of self-destruction [italics mine]. Dr. Sergei Popov saw real potential here.
He would not bother looking for a naturally occurring molecule that could trigger this process. He would make one. Popov spliced a fragment of myelin basic protein into legionella—the bacterium that causes Legionnaire’s Disease—creating a “chimera,” named for the mythical creature with a lion’s head, goat’s body and serpent’s tail. Inside Popov’s new constructed chimera was what amounted to a living “nano-bomb”—molecular contraband that could theoretically cause MS. When Popov infected guinea pigs with his chimera, the immune system cleared the legionella, and, just as he predicted, the myelin molecule smuggled into the guinea pigs inside of his microbial Trojan horse germ initiated a second wave of disease. This stealth germ caused experimental allergic encephalomyelitis, the animal version of MS. Popov felt as proud as a new parent. He could not wait to show “the client.”
“The client” is what VECTOR scientists called the Soviet Army officers who commissioned their biological warfare research projects. “Their initial response was rather discouraging,” says Popov, “because they did not see the fast onset of symptoms.” What the generals were accustomed to seeing was a germ with an immediate and catastrophic effect, but when they came back a few weeks later and saw the guinea pigs crippled MS, they recognized Popov’s creation for what it was—a biological time bomb. Soviet scientists then constructed another one of these time bombs with a virus. They chose vaccinia, the non-lethal cousin of smallpox. Popov, who is now living in America, believes the “final construct” for this viral time bomb was not vaccinia, but smallpox itself. In any case, it worked. “The client” had seen enough. The generals were sold on the idea. “The Russian Ministry of Defense wanted us to construct these designer germs, using myelin basic protein from monkeys and humans,” says Popov. “That would create a human version of the disease.”
Molecular mimicry, seen for its diabolical potential as a weapon by the Soviets as far back as the 1980s, also applies to SQUALENE [caps mine]. But the real problem with using squalene, of course, is not that it mimics a molecule found in the body; it is the same molecule. So what American scientists conceived as a vaccine booster was another “nano-bomb,” instigating chronic, unpredictable and debilitating disease [italics mine]. When the National Institutes of Health (NIH), argued that squalene would be safe because it is native to the body, just the opposite was true. Squalene’s natural presence in the body made it one of the most dangerous molecules injected into human beings [italics mine]. When UCLA Medical School’s Michael Whitehouse and Frances Beck injected squalene combined with other materials into rats and guinea pigs back in the 1970s, few oils were more effective at causing the animal versions of ARTHRITIS, and MULTIPLE SCLEROSIS [caps mine]. By the late 1990s, Sweden’s Karolinska Institute proved that injecting squalene all by itself could cause arthritis. The Polish Academy of Sciences proved that squalene alone could severe neurological damage. Now Tulane University Medical School and its ardent intellectual adversary—the Army’s Col. Carl Alving—have both shown that the immune system makes antibodies to squalene, but only after it is injected [italics mine].
For Squalene’s proponents in the U.S. Army and the NIH, this has been a relentless march towards an unpalatable truth. By adding squalene to their new anthrax vaccine, they did not make a better vaccine; they made a biological weapon [italics mine]. The anti-squalene antibodies in sick U.S. and British military personnel are evidence that military experiments may have caused more casualties with its new anthrax vaccine than have been caused by anthrax weapons since they were first used by the Japanese Army in the 1940s.
The above is an excerpt from Gary Matsumoto’s book (with modifications):
VACCINE.A
The Covert Government Experiment
That’s Killing Our Soldiers
and Why GI’s Are Only the First Victims
books.google.com/books?id=Irw82Iv5nyoC&a…e&q=&f=false
CANADA’S VACCINE MAKER says single dose of ADJUVANTED VACCINE protective.
September 14, 2009 – THE CANADIAN PRESS
[caps & bolding mine]
TORONTO – A shot of swine flu vaccine that is about a third of the size of a standard dose is protective when BOOSTED WITH an additive called an ADJUVANT, CANADA’S PANDEMIC VACCINE MANUFACTURER (GlaxoSmithKline) said Monday.
A single shot containing 5.25 micrograms of VACCINE and the company’s AS03 ADJUVANT had a SPIKE in ANTIBODY LEVELS thought to signal protection
[caps & bolding mine].
MP has H1N1 concerns.
CBC News – September 14, 2009
An NDP MP from Winnipeg: Judy Wasylycia-Leis wants to know what measures Elections Canada has in place to safeguard voters from the spread of swine flu, considering an election poses significant health risks with large public events and many people coming into contact during canvassing…hmmm
(hmmm-mine).
$400M contract goes to GlaxoSmithKline factory in Quebec City.
August 6, 2009 – CBC News.
Canada to order 50.4 million H1N1 (SWINE FLU) vaccine doses – One dose should be enough, because: GlaxoSmithKline is using an additive (AS03 – SQUALENE based) known as ADJUVANT. Adjuvants are used to boost immune response from vaccines [italics, caps and info on AS03 mine].
THE WORLD HEALTH ORGANIZATION (WHO) recommends countries should use SWINE FLU vaccines with ADJUVANTS [caps mine] – to stretch the global supply of the vaccines.
August 4, 2009 – THE CANADIAN PRESS
Flu vaccines in Europe often contain adjuvants [italics and underline mine].
The European Medicines Agency has previously said swine flu vaccines based on a pre-approved bird flu vaccine could be licensed within five days, even without extensive testing in humans.
In the United States, there are no licensed flu vaccines with adjuvants – The U.S. has ordered $979 million worth of bulk vaccine and Novartis’ adjuvant (MF59®) [italics and underline mine].
Boosting compounds called adjuvants complicate licensing of pandemic vaccines.
July 28, 2009 – THE CANADIAN PRESS
Neither country, CANADA and the UNITED SATES, has licensed flu vaccines with adjuvants in them before, making the addition of the oil-and-water emulsions a potential hurdle to fast-track pandemic vaccines [italics & bolding mine].
MF59; is a sub-micron oil-in-water emulsion of a squalene, polyoxyethylene sorbitan monooleate (TweenTM 80) and sorbitan trioleate. SQUALENE is a natural organic compound originally obtained from shark liver oil and a biochemical precursor to steroids. The “MF59” adjuvant was developed by Chiron Corp., a company acquired by Novartis. MF59 is approved in Europe and is found in several vaccines; such as an influenza vaccine manufactured by Novartis. It has also been licensed to other companies and is being actively tested in vaccine trials [bolding & caps mine].
http://www.whale.to/vaccines/mf59_h.html
Information compiled and provided by Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
[...] in Germany by GSK show that a single injection of a 5.25 mcg dose combined with their ASO3 adjuvant gave a robust immune response 12 days after immunization in 98% of the healthy volunteers aged 18 [...]
Received 11 February 2003;
revised 12 April 2003;
accepted 2 May 2003. ;
Available online 11 June 2003.
Abstract
Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund’s adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNFα production 2–3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies.
The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon’s adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WHC-48TMCJ6-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1018959749&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1265afaf82232cd896af7e8b4b1e928f
Information compiled and provided by Christopher-Peter: Maingot; without prejudice, malice aforethought, ill will, vexation, or frivolity.
[...] discussed on this blog back on May 18th, an adjuvant may become mandatory for translating the available flu vaccine manufacturing capacity [...]