Posted on Sat, Oct. 29, 2005

http://www.duluthsuperior.com/mld/duluthsuperior/business/technology/13029338.htm

Big boost for anti-flu fight

TESTS SHOW CHIRON ADDITIVE MAKES VACCINE MORE EFFECTIVE

By Steve Johnson

Mercury News


A Chiron product that boosts the body's immune response to viruses may stretch dramatically the skimpy supplies of vaccine available to combat a potential bird-flu pandemic.

In preliminary federal tests of a Chiron vaccine reported Friday for one of the bird-flu strains, the company's immune-system additive appeared to make the vaccine effective in doses as little as 3.75 micrograms. That is nearly 50 times less than the amount needed for the primary bird-flu vaccine, available from Sanofi-Aventis of France, to be effective.

Among those encouraged by the Chiron test is Cornelia Dekker, who directs a vaccine program at Stanford University and is on the federal government's National Vaccine Advisory Committee.

``It's a very promising first step,'' said Dekker, who had been a research executive at Chiron before leaving in 1997. If the additive, or adjuvant, also significantly reduces the dose needed for the primary bird-flu vaccine, she added, ``it would conceivably make it possible to provide more vaccine more quickly.''

Direct comparisons between the two vaccines from Chiron and Sanofi are difficult because they target different flu-virus strains. Sanofi's vaccine is aimed at the virulent H5N1 virus, while Chiron's vaccine is aimed at the less prevalent H9N2 strain.

Still, one federal health official said Friday it was likely that Chiron's immune booster would prove equally effective when it's tested in small doses of vaccine for the H5N1 strain in the next few months.

Although more tests are needed to confirm this, ``the data are rather impressive,'' said Anthony Fauci, head of the National Institute for Allergy and Infectious Diseases, the agency involved in the Chiron tests. ``It's really quite encouraging.'' Flu vaccines work by triggering a person's antibodies to fight the virus. Because most people have been exposed to the usual seasonal forms of the flu, their immune systems quickly respond when they encounter it. But because the avian flu represents a new threat to humans, experts say, it probably will take a large dose of vaccine to stimulate an immune response, unless a booster is added.

In the Chiron tests, the company's vaccine and its immune system additive -- the MF59 adjuvant -- were injected into 96 people, none of whom was exposed to the virus, said Chiron spokeswoman Alison Marquiss. The additive's effectiveness was evaluated by measuring the test subjects' antibody responses. Chiron has been using the MF59 adjuvant for years in its Fluad vaccine, made in Italy and sold in Europe and other places outside the United States. It is primarily intended to help older people with balky immune systems develop antibodies to seasonal flu viruses, Marquiss said, adding that the MF59-bolstered vaccine has a good safety record.

Walter Orenstein, associate director of the Emory Vaccine Center in Atlanta, agreed. ``It represents something important,'' he said of Chiron's adjuvant. ``It's a way of trying to make more with less.''

http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/5978

TORONTO, June 20 - An investigational oil-and-water adjuvant for flu vaccines -- tested in conjunction with a vaccine against avian flu -- is safe, a researcher said here.  Explain to interested patients that vaccines aimed at the H5N1 avian flu have been shown to create an immune response, but only at very high doses, which would be a problem if they were needed to treat large numbers of people.


Note that this study suggests an experimental oil-and-water emulsion, when used with the vaccine can help it provide better protection at lower doses.


This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed publication. Tested in more than 5,000 volunteers, the adjuvant (dubbed AS) had significantly higher rates of local and general adverse events than a placebo, but most of them were mild, Ripley Ballou, M.D., of GlaxoSmithKline Biologicals in Belgium told attendees at the Options for the Control of Influenza meeting. Rates of withdrawal in the adjuvant arm of the randomized phase III safety trial were only 0.5% higher than in the placebo arm, he said, mainly because of pain at the injection site that dissuaded participants from returning for a second dose.


The issue of adjuvant safety has arisen because most of the candidate vaccines against the H5N1 strain of avian flu require very large doses of antigen to create an immune reaction. Use of an adjuvant could make a scarce vaccine go further among the population-provided it was safe.  A standard adjuvant, aluminum potassium sulfate or alum, is known to be safe, but does not strongly enhance the immunogenicity of the vaccines, so the researcher turned to an older idea - oil and water emulsions. Dr. Ballou and colleagues randomized 5,071 volunteers (on a two-to-one basis) to get one dose of the seasonal Fluarix vaccine without adjuvant or two 15-microgram doses of an experimental H5N1 vaccine, together with the adjuvant.

Earlier studies had already shown that even 3.5 micrograms of the vaccine, combined with adjuvant, led to a high antibody response, Dr. Ballou said.  The researchers found that common reactions to all vaccines were significantly higher in the H5N1 group than in the controls - redness: 38.2% versus 27.8%, swelling: 33.1% versus 17.5%, and induration: 34.4% versus 19.1%. The incidence of ecchymosis was 9.6% versus 5.8%. The most common general adverse effects, as solicited by the researchers, were also higher in the H5N1 group - fatigue: 51.9% versus 30.8%, myalgia: 50.0% versus 24.6%, and headache: 46.9% versus 31.2%. The withdrawal rate in the control group was 2.52% and 3.55% in the H5N1 group. Three withdrawals in the H5N1 groups were related to a serious adverse event (and none in the control group) but the events were not considered to be related to the study medication.

Oil and water emulsions date back to the 1950s, according to vaccine researcher John Treanor, M.D., of the University of Rochester Medical Center in Rochester, N.Y. They fell out of favor because of some serious side effects, including the development of sterile abscesses at the injection site and the suspicion - later disproved - that they caused plasmacytomas, Dr. Treanor said.  The current generation of emulsions, on the other hand, appears not to have such serious adverse effects, he said, and may prove valuable, especially in the event of a flu pandemic.  "I think it's quite definitive that oil and water emulsions are very, very effective in enhancing the antibody response to neo-antigens like a flu vaccine," he said. But researchers and clinicians still have to "think hard about what constitutes an acceptable safety profile" for such adjuvants. The increase in the withdrawal rate for the Glaxo adjuvant "sounds acceptable" in a trial of 5,000 people, "but if you vaccinated a million people, that would be 5,000 people who wouldn't come back for the second dose," Dr. Treanor said.


On the other hand, in a pandemic, people might be more willing to accept a painful second injection, he added.


This study was supported by GlaxoSmithKline Biologicals of Belgium. Dr. Ballou is an employee of the company.
 

Vaccine May Be More Dangerous Than Swine Flu

Tuesday, July 7, 2009 9:54 AM

By: Dr. Russell Blaylock Article Font Size

An outbreak of swine flu occurred in Mexico this spring that eventually affected 4,910 Mexican citizens and resulted in 85 deaths. By the time it spread to the United States, the virus caused only mild cases of flu-like illness. Thanks to air travel and the failure of public health officials to control travel from Mexico, the virus spread worldwide. Despite predictions of massive numbers of deaths and the arrival of doomsday, the virus has remained a relatively mild disease, something we know happens each year with flu epidemics.

Worldwide, there have only been 311 deaths out of 70,893 cases of swine flu. In the United States, 27,717 cases have resulted in 127 deaths. Every death is a tragedy, but such a low death rate should not be the basis of a draconian government policy. It is helpful to recall that the Centers for Disease Control with the collusion of the media, constantly tell us that 36,000 people die from the flu each year, a figure that has been shown to be a lie. In this case, we are talking about 300 plus deaths for the entire world.

This virus continues to be an enigma for virologists. In the April 30, 2009 issue of Nature, a virologist was quoted as saying,“Where the hell it got all these genes from we don’t know.” Extensive analysis of the virus found that it contained the original 1918 H1N1 flu virus, the avian flu virus (bird flu), and two new H3N2 virus genes from Eurasia. Debate continues over the possibility that swine flu is a genetically engineered virus.

Naturally, vaccine manufacturers have been in a competitive battle to produce the first vaccine. The main contenders have been Baxter Pharmaceuticals and Novartis Pharmaceuticals, the latter of which recently acquired the scandal-ridden Chiron vaccine company. Both of these companies have had agreements with the World Health Organization to produce a pandemic vaccine. The Baxter vaccine, called Celvapan, has had fast track approval. It uses a new vero cell technology, which utilizes cultured cells from the African green monkey. This same animal tissue transmits a number of vaccine-contaminating viruses, including the HIV virus.

The Baxter company has been associated with two deadly scandals. The first event occurred in 2006 when hemophiliac components were contaminated with HIV virus and injected in tens of thousands of people, including thousands of children. Baxter continued to release the HIV contaminated vaccine even after the contamination was known.

The second event occurred recently when it was discovered that Baxter had released a seasonal flu vaccine containing the bird flu virus, which would have produced a real world pandemic, to 18 countries. Fortunately, astute lab workers in the Czech Republic discovered the deadly combination and blew the whistle before a worldwide disaster was unleashed.


Despite these two deadly events, WHO maintains an agreement with Baxter Pharmaceuticals to produce the world’s pandemic vaccine.


Novartis, the second contender, also has an agreement with WHO for a pandemic vaccine. Novartis appears to have won the contract, since their vaccine is near completion. What is terrifying is that these pandemic vaccines contain ingredients, called immune adjuvants that a number of studies have shown cause devastating autoimmune disorders, including rheumatoid arthritis, multiple sclerosis and lupus.


Animal studies using this adjuvant have found them to be deadly. A study using 14 guinea pigs found that when they were injected with the special adjuvant, only one animal survived. A repeat of the study found the same deadly outcome.


So, what is this deadly ingredient? It is called squalene, a type of oil. The Chiron company, maker of the deadly anthrax vaccine, makes an adjuvant called MF-59 which contains two main ingredients of concern—squalene and gp120. A number of studies have shown that squalene can trigger all of the above-mentioned autoimmune diseases when injected.


The MF-59 adjuvant has been used in several vaccines. These vaccines, including tetanus and diphtheria, are the same vaccines frequently associated with adverse reactions.


I reviewed a number of studies on this adjuvant and found something quite interesting. Several studies done on human test subjects found MF-59 to be a very safe immune adjuvant. But when I checked to see who did these studies, I found—to no surprise—that they were done by the Novartis Pharmaceutical Company and Chiron Pharmaceutical Company, which have merged. They were all published in “prestigious” medical journals. Also, to no surprise, a great number of studies done by independent laboratories and research institutions all found a strong link between MF-59 and autoimmune diseases.


Squalene in vaccines has been strongly linked to the Gulf War Syndrome. On August 1991, Anthony Principi, Secretary of Veterans Affairs admitted that soldiers vaccinated with the anthrax vaccine from 1990 to 1991 had an increased risk of 200 percent in developing the deadly disease amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease. The soldiers also suffered from a number of debilitating and life-shortening diseases, such as polyarteritis nodosa, multiple sclerosis (MS), lupus, transverse myelitis (a neurological disorder caused by inflammation of the spinal cord), endocarditis (inflammation of the heart’s inner lining), optic neuritis with blindness and glomerulonephritis (a type of kidney disease).


Because squalene, the main ingredient in MF-59, can induce hyperimmune responses and induce autoimmunity, a real danger exists for prolonged activation of the brain’s immune cells, the microglia. This type of prolonged activation has been strongly associated with such diseases as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, ALS and possibly vaccine-related encephalitis. It has been shown that activation of the systemic immune system, as occurs with vaccination, rapidly activates the brain’s microglia at the same time, and this brain inflammation can persist for long periods.


So, how would the gp120 get into the brain? Studies of other immune adjuvants using careful tracer techniques have shown that they routinely enter the brain following vaccination. What most people do not know, even the doctors who recommend the vaccines, is that most such studies by pharmaceutical companies observe the patients for only one to two weeks following vaccination—these types of reactions may take months or even years to manifest.


It is obvious that the vaccine manufacturers stand to make billions of dollars in profits from this WHO/government-promoted pandemic. Novartis, the maker of the new pandemic vaccine, recently announced that they would not give free vaccines to impoverished nations—everybody pays.


One must keep in mind that once the vaccine is injected, there is little you can do to protect yourself—at least by conventional medicine. It will mean a lifetime of crippling illness and early death.


There are much safer ways to protect oneself from this flu virus, such as higher doses of vitamin D3, selective immune enhancement using supplements, and a good diet.
http://www.newsmax.com/health/vaccine_swine_flu/2009/07/07/232717.html
© 2009 Newsmax. All rights reserved.

 

WO/1999/034825) FERTILITY IMPAIRING VACCINE AND METHOD OF USE

This application claims the benefit of U. S. Provisional Application No. 60/070,375, filed January 2,1998, U. S. Provisional Application No. 60/071,406, filed January 15,1998

“The vaccine of the invention preferably additionally includes an immunological adjuvant to enhance the immunological response of the subject to the glycoprotein antigen. Examples of adjuvants include Freund’s Complete Adjuvant, Freund’s Incomplete Adjuvant, and an adjuvant comprising an immunostimulant such as synthetic trehalose dicorynomycolate (STDCM) and an oil such as squalene oil (see P. Willis et al., J. Equine Vet. Sci., 14,364-370 (1994)). An adjuvant comprising synthetic trehalose dicorynemycolate, squalene oil, and a surfactant such as lecithin is preferred. Lecithin typically includes phosphatidyl choline. In a preferred embodiment the vaccine comprises oil, preferably a biodegradable oil such as squalene oil. Typically, the vaccine is prepared using an adjuvant concentrate which contains lecithin in squalene oil. The aqueous solution glycoprotein is typically a phosphate-buffered saline (PBS) solution, and additionally preferably contains Tween 80.”

Abstract:

A vaccine comprising an antigen derived from a zona pellucida glycoprotein is effective to impair fertility in animals, preferably carnivores. The vaccine can be used as an immunosterilant or an immunocontraceptive.

http://www.wipo.int/pctdb/en/wo.jsp?wo=1999034825

Description:

http://www.wipo.int/pctdb/en/wo.jsp?IA=US1998027658&wo=1999034825&DISPLAY=DESC

Squalene References, pages 339-344, Vaccine A: The Covert Government Experiment that’s Killing our Soldiers and Why GI’’s are Only the First Victims, by Gary Matsumoto, 2004 – Basic Books,. Library of Congress Catalogue # ISBN 0-465-04400-X

Squalene Induces Autoimmune Disease in Animals
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1 4. Gajkowska B, Smialek M, Ostrowski RP, Piotrowski P, Frontczak-Baniewicz M
[The Laboratory of the Ultrastructure of the Nervous System, Medical Research Centre, Polish Academy of Sciences,S Pawinskiego Street, 02-106 Warsaw, Poland], ‘The experimental squalene encephaloneuropathy in the rat,” Experime­tal and Toxicologic Pathology, (1999) January; 5:75-80.
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16. Carlson BC, ]annson AM, Larsson A, Bucht A, Lorentzen]C [Department of Medicinee, Karolinska Institutet, Stockholm, Sweden], “The endogenous adjuvant squa­
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21. Gherardi RK [Groupe Nerf-Muscle, Departement de Pathologie, Hopital Henri Mondor, Creteil], “Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome,” Revue Neurologique (Paris), (2003) Feb; 159(2): 162-4.
22. Backdahl L, Ribbihammar U, Lorentzen ]C [Center for Molecular Medicine, Karolinska Institutet, Stockholm], “Mapping and functional characterization of rat chromosome 4 regions that regulate arthritis models and phenotypes in congenic strains,” Arthritis and Rheumatism, (2003) Feb;48(2):551-9.
23. Satoh M, Kuroda Y, Yoshida H, Behney KM, Mizutani A, Akaogi], Nacionales DC, Lorenson TD, Rosenbauer R], Reeves WH [Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville], “Induction of lupus autoantibodies by adjuvants,” Journal of Autoimmunity, (2003) Aug;21(l):1-9.
24. Kuroda Y, Akaogi ], Nacionales DC, Wasdo SC, Szabo N], Reeves WH, Satoh M [Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville], “Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil,” Toxicological Sciences, (2004) Apr;78(2):222-8.
25. Kuroda Y, Nacionales DC, Akaogi J, Reeves WH, Satoh M [Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville], “Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine,” Biomedicine & Pharmflcotherapy, (2004), Jun;(5S)5:325.37.
26. Holm BC, Lorentzen JC, Bucht A [Diabetes Research, Immunology Unit, Department of Endocrinology, Lund University, Malmo University Hospital, Stockholm], “Adjuvant oil induces waves of arthritogenic lymph node cells prior to arthritis on. set,” Clinical and Experimental Immunology, (2004) Jul;137(1):59.64.

Adverse Reactions in Humans to Experimental Vaccines Containing Squalene
27. Keitel W, Couch R, Bond N., Adair S, Van Nest G, Dekker C [Baylor College of Medicine, Department of Microbiology and Immunology, One Baylor Plaza, Hous. ton, Texas 77030], “Pilot evaluation of influenza virus vaccine (IW) combined with adjuvant,” Vaccine, (1993);11(9):909.913; “[See also Nos. 27 & 31);

Squalene Stimulates the Immune System
28. Ott G, Barchfield GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G
[Chiron Corporation, Emeryville, California 9460S], “MF59. Design and evaluation of a safe and potent adjuvant for human vaccines,” Pharm Biotechnol, (1995);6:277. 96.
29. Ott G, Barchfield GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G [Chiron Corporation, Emeryville, CA 9460S], “MF59. Design and Evaluation of a Safe and Potent Adjuvant for Human Vaccines,” Vaccine Design: The Subunit and Adjuvant Approach (Monograph), (1995) Chapter 1 0:277 .311.
30. Ott G, Barchfield GL, Van Nest G [Chiron Corporation, EmeryvilIe, CA 9460S], “Enhancement of humoral response against human influenza vaccine with the simple submicron oil/water emulsion adjuvant MF59,” Vaccine, (1995) Nov; 13(16): 1557.62.
31. O’Hagan DT, Ott GS, Van Nest G [Chiron Corporation, Emeryville, CA 94704], “Recent advances in vaccine adjuvants: the development of MF59 emulsion and polymeric microparticles,” Molecular Medicine Today, (1997) Feb; 3(2):69-75.
32. Allison AC [Suromed Corporation, 1060 East Meadow Circle, Palo Alto, California 94303], “Squalene and squalane emulsions as adjuvants,” Methods (1999) Sept; 19( 1 ):S7 .93.

How the Immune System Processes Squalene
33. Depuis M, Murphy TJ, Higgins D, Ugozzoli M, Van Nest G, Ott G, McDonald DM
[Cardiovascular Research Institute, University of California, San Francisco, CA 94143], “Dendritic cells internalize vaccine adjuvant after intramuscular injection,” Cellular Immunology, (1998) May 25; 186(1): 18-27.
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35. Depuis M, Denis-Mize K, LaBarbaraA, Peters W, Charo IF, McDonald OM, Ott G [Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, CA 94143], “Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis,” European Journal of Immunology, (2001) Oct;31(10):291O-8.

Specificity of Antibody Response to Squalene
36. Asa PB, Cao Y, Garry RF [Department of Microbiology and Immunology, Tulane Medical School, 1430 Tulane Avenue, New Orleans, Louisiana 70112], “Antibodies to Squalene in Gulf War Syndrome,” Experimental and Molecular Pathology (2000) Feb;68(1):55-64.
37. Matyas GR, Wasseff NM, Rao M, Alving CR [Department of Membrane Biochemistry, Walter Reed Army Institute of Research, 20910-7500, Silver Spring, MD], “Induction and detection of antibodies to squalene,” Journal of Immunological Methods (2000) Nov 1;245(1-2):1-14.
38. Alving CR, Grabenstein JD [Walter Reed Army Institute of Research and Anthrax Vaccine Immunization Program Office], “RE: Antibodies to squalene in Gulf War Syndrome,” Experimental and Molecular Pathology (2000) Jun;68(3): 196-8.
39. Asa PB, Cao Y, Garry RF [Department of Microbiology and Immunology, Tulane Medical School, 1430 Tulane Avenue, New Orleans, Louisiana 70112], “Reply,” Experimental and Molecular Pathology (2000) Jun;68(3): 197-8.
40. Asa PB, Wilson RB, Garry RF [Department of Microbiology and Immunology, Tulane Medical School, 1430 Tulane Avenue, New Orleans, Louisiana 70112], “Antibodies to Squalene in recipients of anthrax vaccine,” Experimental and Molecular Pathology (2002) Aug;73(1): 19-27.
41. Matyas G, Rao M, Alving C [Department of Membrane Biochemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, 20910-7500, Silver Spring,
MD, USA], “Induction and detection of antibodies to squalene. II. Optimization of
the assay for murine antibodies,” Journal of Immunological Methods (2002) Sep 15; 267(2):119.
42. Matyas GR, Rao M, Pittman PR, Burge R, Robbins IE, Wassef NM, Thivierge B, Alving CR [Department of Membrane Biochemistry, Walter Reed Army Institute of Research], “Detection of antibodies to squalene: III. Naturally occurring antibodies to squalene in humans and mice,” Journal of Immunological Methods, (2004) Mar;286(102):47-67.


Ingested Squalene Is Processed Differently from Injected Squalene
43. Tilvis RS, Miettinen TA [Department of Medicine, University of Helsinki, Helsinki, Finland], “Absorption and metabolic fate of dietary 3H-squalene in the rat,” Lipids, (1983) Mar;18(3):233-8.
44. Gylling H, Miettinen TA [Second Department of Medicine, University of Helsinki, Helsinki, Finland], “Postabsorptive metabolism of dietary squalene,” Atherosclerosis, (1994) April; 106(2): 169-78.
45. Relas H, Gylling H, Miettinen TA [Department of Medicine, University of Helsinki, Helsinki, Finland], “Effect of stanol ester on postabsorptive squalene and retinyl palmitate,” Metabolism, (2000) April;49(4):473-8.

Detecting Squalene in Anthrax Vaccine Adsorbed [BioThrax] and U.K. Anthrax Vaccine
46. Spangood RJ, Wu B, Sun M, Lim P, Ellis WY [SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025], “Development and application of an analytical method for the determination of squalene in formulations of anthrax vaccine adsorbed,” Journal of Pharmaceutical and Biomedical Analysis (2002) June 20;29(1­2):183-93.
47. May JC, Del Grosso A, Swartz L, Progar 11, “Chemical Test Results for Michigan Department of Public Health, Anthrax Vaccine Adsorbed, Lots FAV020 and FAV 030,” Department of Health and Human Services, Food and Drug Administration, CBER, Lab Report, Personal Communication to Neil Goldman, Ph.D., 25 June 1999, pg. 1-6.
48. Wood D [Scientific Analysis Laboratories Ltd., Medlock House, New Elm Road, Manchester M3 4JH, United Kingdom], “The Determination of Squalene in a Vaccine Sample, Scientific Analysis Laboratories, SAL Report 34120E,” Scientific Analysis Laboratories Ltd., Lab Report, Personal Communication to Asif Hasan, Granada Television, 26 February 2003, pg. 1-6;.







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