Audibert F, Chedid L.

Genetic, endocrine and immunological factors are probably involved in adjuvant polyarthritis. The nature of the vehicle and of the mycobacterial components administered also has a major influence. It was originally assumed that arthritogenicity and adjuvanticity of mycobacterial fractions such as wax D were intimately related. Our previous findings showed that the water soluble adjuvant (WSA) of M.smegmatis which could substitute for mycobacterial cells in Freund’s complete adjuvant and induce delayed hypersensitivity was not arthritogenic in the Wistar rat. We have since observed that auto-immune diseases could be elicited by WSA. Therefore experiments were repeated using the very susceptible Lewis strain. The activity of cord factor and of various mycobacterial preparations suspended in mineral or in peanut oil was also evaluated in mice and in normal or hypophysectomized rats. Our present findings confirm the absence of arthritogenicity of WSA in the Lewis strain. They also indicate that cord factor with WSA does not suffice to induce a generalized adjuvant disease, but that a mycobacterial component which could be susceptible to lysozyme treatment is required also. However, the local inflammation of the injected limb was produced by a preparation of cord factor administered in mineral or even in peanut oil. This was observed in normal or hypophysectomized rats and in Swiss mice which were not susceptible to the generalized disease.

PMID: 181972 [PubMed – indexed for MEDLINE]

http://www.eswi.org/Bulletin_April_1997.cfm

Potential Role for Adjuvanted Influenza Vaccine
Adjuvanted inactivated influenza virus vaccines (AIVV) were developed and administered to thousands of people during the mid-1940s and continuing to the mid-1970s. These studies demonstrated increased antibody responses and increased protection for AIVV when compared to aqueous vaccines and indicated that use of such vaccines could increase protection during interpandemic periods. Moreover, the enhanced immunogenicity obtained with lower doses suggested that the number of vaccine doses available for use against pandemic influenza could be considerably increased while still obtaining acceptable responses.

Increased immunogenicity for AIVV was reported in 1945; a four-fold enhancement of serum haemagglutination-inhibiting (HAI) antibody titres was seen when mineral oil was mixed with aqueous vaccine.

This finding was confirmed by others and the study of adjuvanted vaccines was then expanded. Most studies employed mineral oil or peanut oil (adjuvant 65, Merck & Co.) containing an emulsifier or an aluminium compound. The aluminium compounds varied in their immune-enhancing effects, but the two oil adjuvants consistently enhanced responses. Mean serum HAI antibody titres for two representative studies are shown in Table 1.

The magnitude of the increase (=>6­8 fold), the pattern for increase in all age groups including the elderly, the fact that results are similar for two type A subtypes, and that the greater response for adjuvant occurred with a lower antigen dose are of particular interest. Responses reported for influenza type A and type B viruses were similar. In one study, antibody was also measured in nasal secretions where frequencies of rises for AIVV increased from 47% to 78% and the geometric mean titre (GMT) from 0.4 to 1.0.

Thus, oil adjuvant vaccines can increase serum antibody significantly in all age groups when compared to comparable aqueous inactivated influenza virus vaccines. Moreover, antibody increases in secretions appear to parallel those in serum. The overall antibody response has also broadened to include more related variants and to persist for up to three years. Early reactogenicity was increased for AIVV when given subcutaneously but reduced with intramuscular administration.

The enhanced immunogenicity of oil adjuvant vaccine was accompanied by enhanced protection. Using an A/Hong Kong (H3N2) virus challenge of volunteers, Freestone et al. [3] reported increased serum and nasal secretion neutralising antibody for a mineral oil adjuvant vaccine group (3500 HA unit dose) compared with aqueous split product vaccine at an 8000 HA unit dose. Virus shedding and illness after challenge were similar for split vaccine and controls but significantly lower for oil adjuvant vaccine. A summary of results from field trials with mineral oil adjuvant vaccine among USA military personnel is shown in Table 2.

Despite substantial increases in immunogenicity and effectiveness for oil adjuvant vaccines, their use was discontinued. Reports of increased tumour formation in animals from mineral oil and Arlacel A (the emulsifier), and the occurrence of nodules, cysts, or sterile abscesses in a low proportion of recipients (3­23 per 10,000 vaccinees) were contributing factors. It is of interest that an 18-year follow-up of 18,000 oil adjuvant vaccinees did not reveal any increase in occurrences of cancer [5].

The recent development of a variety of experimental adjuvants and the burgeoning market for influenza virus vaccines has stimulated renewed interest in AIVV. Recent clinical trials have employed liposomes, monophosphoryl lipid A, Qs21 (active component of the saponin Quil A) and MF 59 (a synthetic adjuvant containing squalene). In experimental animals, significantly enhanced immunogenicity and efficacy have been observed for each of these; in humans, the response so far is only marginal. Clearly, the level of enhancement reported is considerably below that reported previously for oil adjuvant vaccine.

Improvements in the effectiveness of inactivated influenza virus vaccines, not only to enhance their performance but also to maintain and improve their reputation as a valuable preventive measure for influenza, are needed. Adjuvants can potentially enhance the effectiveness of current vaccines for both interpandemic and pandemic influenza. It is, therefore, important that efforts continue towards the identification of an adjuvant preparation that can approach the degree of enhancement conveyed in the past by oil adjuvant vaccines.

R.B. Couch
Department of Microbiology and Immunology
Baylor College of Medicine
Houston, Texas, USA

References

Hennessy AV, Davenport FM. Relative merits of aqueous and adjuvant influenza vaccines when used in a two-dose schedule. Public Health Rpts 1961; 76: 411­419. Stokes J Jr, Weibel RE, Drake ME, et al. New metabolizable immunologic adjuvant for human use. N Engl J Med 1964; 271: 479­487.
Freestone DS, Hamilton-Smith S, Schild EC, et al. Antibody responses and resistance to challenge in volunteers vaccinated with live attenuated, detergent split and oil adjuvant A2/Hong Kong/68 (H3N2) influenza viruses. J Hyg Camb 1972; 70: 531­543. Davenport FM. Applied immunology of mineral oil adjuvants. J Allergy 1961; 32: 177­189. Beebe GW, Simon AH, Vivona LS. Long-term mortality follow-up of army recruits who received adjuvant influenza virus vaccine in 1951­1953. Am J Epidemiol 1972; 95: 337­46.

The Allergy Epidemic

We’ve conquered most childhood infections, but extreme reactions to everyday substances pose a new threat

By Jerry Adler

NEWSWEEK

Sept. 22 issue —  The first indication that something was not quite right with David Adams was subtle, a mild rash around his mouth after nursing.

The Allergy Epidemic

We’ve conquered most childhood infections, but extreme reactions to everyday substances pose a new threat

By Jerry Adler

NEWSWEEK

Sept. 22 issue —  The first indication that something was not quite right with David Adams was subtle, a mild rash around his mouth after nursing.

LUCKILY, THE SECOND CLUE, at the age of 3 months, was not so subtle: angry hives that erupted over his entire body during a plane trip. After the family returned home to Georgia, a specialist determined that David was among the 6 to 8 percent of children under the age of 3 with an allergy to food—in his case, peanuts.

His sensitivity was so acute that the hives may have been caused by the residue of peanuts on his parents’ fingers, and the rash by his mother’s eating a peanut-butter sandwich and excreting tiny amounts of peanut protein in her breast milk. What made the episode lucky was this: on a day two years later, when David began vomiting and gasping after chomping an energy bar that had escaped his parents’ anti-peanut scrutiny, his mother could inject him with epinephrine and save his life. Implausible as it seems, David’s condition is at the cutting edge of modern pediatric medicine, right up there with hay fever.

OUT OF SYNC

If a popular magazine had run a children’s health issue a hundred years ago, the first article might have been about diphtheria or cholera—external threats that the West has largely conquered by antibiotics and sanitation. (Hmmm…not vaccines?) Instead we are examining allergies, a self-generated danger, the result of an immune system out of sync with its surroundings. These are among the leading challenges of the next century, a threat that may in part be an unintended consequence of our triumph over the infectious scourges of the past.

Click here to read the transcript of Dr. Alan Woolf’s live talk on what makes parents anxious about their kids.

Speaking of hay fever, or “seasonal allergic rhinitis,” the incidence of this annoying sensitivity to tree, grass or ragweed pollen has increased remarkably just since 1996—from 6 percent of American children 18 and under to 9 percent, according to the National Center for Health Statistics. All allergies seem to be on the rise, in fact, but “it’s not just that more kids have allergies,” says Dr. Marc Rothenberg, director of allergy and immunology at Cincinnati Children’s Hospital. “The severity of those allergies has also increased.”

An allergy is an overreaction by the immune system to a foreign substance, which can enter the body through a variety of routes. It can be inhaled, like pollen or dander, the tiny flakes of skin shed by domestic animals. It can be injected, like insect venom or penicillin, or merely touch the skin, like the latex in medical gloves. Or it can be ingested. According to the Food Allergy & Anaphylaxis Network, almost any food can trigger an allergy, although eight categories account for 90 percent of all reactions: milk, eggs, peanuts (technically, a legume), tree nuts, fin fish, shellfish, soy and wheat. (Allergies have nothing to do with the condition known as food intolerance; people who lack an enzyme for digesting dairy products, for instance, may suffer intestinal problems, but they are not allergic to milk.)

For reasons not fully understood, in some people these otherwise harmless substances provoke the same reactions by which the body attempts to rid itself of dangerous pathogens. These may include sneezing, vomiting and the all-purpose localized immune-system arousal known as inflammation. The lungs may be affected; allergies are a leading trigger for asthma attacks. In extreme cases, the reaction involves virtually all organ systems and proceeds to anaphylaxis, a dramatic drop in blood pressure accompanied by extreme respiratory distress that may be fatal without prompt treatment. Which is why, to this day—and possibly for the rest of his life—David Adams never sets foot outside his home without an emergency supply of epinephrine.

GENETIC PREDISPOSITIONS

What can underlie such a self-destructive reaction? An infant who grows violently ill in the presence of as little as one hundredth of a peanut almost surely has some sort of genetic predisposition. Indeed, there is a strong inherited component in allergies. If one parent has an allergy, chances are one in three that the child will be allergic, according to the Asthma and Allergy Foundation of America. If both parents have allergies, the odds rise to 70 percent. But the children aren’t necessarily allergic to the same things as the parents—strongly suggesting that some other factor must be at work as well. And genetics cannot explain the rapid rise in allergies over the past few years or, for that matter, centuries. “The human race hasn’t changed that much genetically in the last 200 years,” since hay fever first came to the attention of doctors a single case at a time, says Dr. Andrew Saxon, chief of clinical immunology at UCLA.

So something must have changed in the environment—specifically, in the environment of developed nations, and especially their cities, where allergies are far more prevalent than in rural China and Africa. One obvious place to look is air pollution. Studies by Saxon and his colleague David Diaz-Sanchez have found a strong correlation between pollutants—diesel exhaust and cigarette smoke—and the development of allergies. Researchers don’t believe pollution is the whole story, though; allergies have continued to climb even as smoking and air-pollution rates have fallen in recent decades. But industrialization has also brought about declines in infectious diseases and close exposure to farm animals. The “hygiene hypothesis” holds that it is precisely these (mostly desirable) trends that have contributed to the rise in allergies. The human immune system, which evolved in a natural environment teeming with hostile bacteria and parasites, finds itself uncomfortably idle in the antiseptic confines of the modern suburb, and, failing to mature properly, takes out its frustration on harmless peanuts and shrimp. Numerous studies have lent support to this general notion, notably one last year that showed a strong negative correlation between allergies and exposure to endotoxins, which are bacterial remains shed by farm animals. Research by Dr. Dennis Ownby of the Medical College of Georgia shows that children growing up with two or more pets, either cats or dogs, had a decreased risk of allergies—and not just to pet dander, but other unrelated allergens as well. But although many researchers accept the hygiene hypothesis in outline, the emerging picture is of “a complicated relationship, where dose and timing of exposure” play important but still uncertain roles, says Dr. Scott Weiss of Harvard.

PLEASE SNEEZE ON ME

So the hygiene hypothesis has yet to generate any concrete prescriptions (unless you count The New England Journal of Medicine’s August 2000 editorial headlined PLEASE, SNEEZE ON MY CHILD). The eventual hope, says Ownby, is for a way to “artificially stimulate the immune system to reduce [allergy] risk without having all these diseases.” Meanwhile, though, researchers are developing new drug therapies that go beyond epinephrine (for emergency treatment of anaphylaxis) and the growing array of over-the-counter antihistamines. (Histamine is a key substance in the cascade of biochemical events that constitute an allergic reaction.) Newer drugs, like Singulair and Xolair—just approved by the Food and Drug Administration in June for allergy-related asthma—block other chemicals in the chain. And even ordinary activated charcoal could be useful in blocking peanut allergies, according to a new study; if taken immediately it may neutralize the allergenic proteins in the stomach.

Pediatricians have also begun taking allergies more seriously. One key bit of advice to mothers is to breast-feed infants exclusively for six months. Delaying children’s exposure to novel foods in this way is the “hallmark for food-allergy prevention,” says the American Academy of Pediatrics. Nursing mothers should also be on the lookout for signs of a secondhand food reaction in their infants, including diarrhea, vomiting or itchy rashes (not counting diaper rash). If these rare reactions occur, the mother may want to avoid drinking milk, or eating eggs, fish, tree nuts and especially peanuts. Peanuts, in fact, are the one food the AAP recommends that a woman avoid, not only while nursing but also while pregnant, because of their allergic potential. For the same reason, the longer you can hold off feeding your child peanut butter, the better: the AAP suggests waiting until 3. Cow’s milk, by contrast, is usually safe after the 1st birthday.

And once an allergy has been diagnosed, the only thing to do is what David Adams’s parents did: draw a cordon sanitaire around the child. Again, this is especially important for peanut allergies. Unfortunately, peanuts and peanut butter are ubiquitous, found in many Asian and Mexican dishes, in baked goods—and in practically every other child’s lunchbox. Peanut-free zones in school lunchrooms have become a vital amenity in many communities, but even so, parents with severely allergic children are constantly on alert—writing to food companies to double-check lists of ingredients, outlawing even innocuous bakery products (a spatula that came into contact with a peanut-butter cookie can transfer a dangerous dose of allergen to an oatmeal-raisin one) and equipping babysitters and teachers with dedicated cell phones and walkie-talkies for emergencies. Milk, another potentially potent allergen, is, if anything, even harder to avoid. “You’re sitting at a [school] cafeteria table and someone across from you spills milk,” says Denise Bunning, of suburban Chicago, describing her nightmare scenario; Bunning’s two sons, Bryan, 9, and Daniel, 7, are both allergic to milk, along with several other foods. At the age of 4, Bryan went into anaphylaxis after eating a jelly worm from a dispenser that had previously held milk-chocolate candies.

Susan Leavitt of New York, whose 13-year-old son, David Parkinson, is allergic to milk products, eggs, fish, nuts and mustard, goes so far as to check out school art supplies; a fourth-grade teacher once mentioned adding eggs to tempera paint for a better texture. There’s a lot he can’t have—pizza, to start with—but a lot of it is stuff you wouldn’t necessarily want your kid to have anyway. And thanks to her vigilance, her home-cooked and pre-frozen meals and New York’s ubiquitous fruit and vegetable markets, David is a healthy, normal boy, an avid skier—and alive.

With Anne Underwood and Karen Springen

© 2003 Newsweek, Inc.

Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil.

Kuroda Y, Akaogi J, Nacionales DC, Wasdo SC, Szabo NJ, Reeves WH, Satoh M.

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.

Although mineral oils are generally considered non-toxic and have a long history of use in humans, the mineral oil Bayol F (incomplete Freund’s adjuvant, IFA) and certain mineral oil components (squalene and n-hexadecane) induce lupus-related anti-nRNP/Sm or -Su autoantibodies in non-autoimmune mice. In the present study, we investigated whether medicinal mineral oils can induce other types of autoantibodies and whether structural features of hydrocarbons influence autoantibody specificity. Three-month old female BALB/c (16-45/group) mice received an i.p. injection of pristane (C19), squalene (C30), IFA, 3 medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas chromatography/mass spectrometry. IFA contained mainly of C15-C25 hydrocarbons whereas MO-HT and MO-S contained C20-C40 and MO-F contained C15-C40. Pristane and n-hexadecane were found in IFA (0.17% and 0.10%, w/v respectively) and MOs (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic antibodies were common in mice treated with MO-F, as well as those treated with pristane, squalene and IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in untreated/PBS, squalene, or IFA treated mice, suggesting that there is variability in the induction of anti-nRNP/Sm vs. -chromatin/DNA antibodies. The preferential induction of anti-chromatin/ssDNA antibodies without anti-nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of autoantibodies are regulated differently. Induction of autoantibodies by mineral oils considered non-toxic also may have pathogenetic implications in human autoimmune diseases.

Vaccine. 1995 Oct;13(14):1263-76.

Adjuvants for human vaccines–current status, problems and future prospects.

Gupta RK, Siber GR.

Massachusetts Public Health Biologic Laboratories, State Laboratory Institute, Boston 02130, USA.

Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. With the use of adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of adjuvants for human vaccines. The biggest issue with the use of adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines.

Publication Types:

	Review
	Review, Tutorial

PMID: 8585280 [PubMed – indexed for MEDLINE]

Yamanaka M, Hiramatsu K, Hirahara T, Okabe T, Nakai M, Sasaki N, Goto N.

Division of Veterinary Microbiology, Kyoto Biken Laboratories, Inc., Japan.

We investigated pathological changes at the injection site in guinea pigs and rats for 16 weeks following a single intramuscular injection of one of the following oil adjuvant emulsions; oil adjuvant ISA-70, Freund’s incomplete adjuvant, Freund’s complete adjuvant, and aluminium phosphate gel. In the animals injected with ISA-70 emulsion prepared by manual shaking, grossly, there was partial thickening of subcutaneous tissue, discoloration of inter-muscular connective tissue, and swelling of the inguinal lymph nodes at 2 and 4 weeks post injection (PI). Histopathologically, ISA-70 injected sites revealed acute inflammatory changes at 72 hrs PI, and peak reactions consisting of macrophage accumulation around oil cysts and fibrosis were observed at 4 weeks PI. These changes were less severe and of shorter duration than those in the other three adjuvants. Guinea pigs and rats injected with materials containing inactivated Newcastle disease virus (NDV) antigen similarly showed an infiltration of plasma cells and lymphocytes in addition to the changes described above. ISA-70 containing NDV antigen induced similar hemagglutination-inhibition titer to that induced by Freund’s incomplete adjuvant.

PMID: 1391179 [PubMed – indexed for MEDLINE]

1: Toxicol Sci. 2004 Jan 12   [Epub ahead of print]

Distinctive Patterns of Autoimmune Response Induced by Different Types of
Mineral Oil.

Kuroda Y, Akaogi J, Nacionales DC, Wasdo SC, Szabo NJ, Reeves WH, Satoh M.

Division of Rheumatology and Clinical Immunology, Department of Medicine,
University of Florida, Gainesville, FL 32610-0221, USA.

Although mineral oils are generally considered non-toxic and have a long history of use in humans, the mineral oil Bayol F (incomplete Freund’s adjuvant, IFA) and certain mineral oil components (squalene and n-hexadecane) induce lupus-related anti-nRNP/Sm or -Su autoantibodies in non-autoimmune mice. In the present study, we investigated whether medicinal mineral oils can induce other types of autoantibodies and whether structural features of hydrocarbons influence autoantibody specificity. Three-month old female BALB/c
(16-45/group) mice received an i.p. injection of pristane (C19), squalene (C30), IFA, 3 medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for  autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas chromatography/mass spectrometry. IFA contained mainly of C15-C25 hydrocarbons whereas MO-HT and MO-S contained C20-C40 and MO-F contained C15-C40. Pristane and n-hexadecane were found in IFA (0.17% and 0.10%, w/v respectively) and MOs (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic
antibodies were common in mice treated with MO-F, as well as those treated with pristane, squalene and IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in untreated/PBS, squalene, or IFA treated mice, suggesting that there is variability in the induction of anti-nRNP/Sm vs. -chromatin/DNA antibodies. The preferential induction of anti-chromatin/ssDNA antibodies without anti-nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of autoantibodies are regulated differently. Induction of autoantibodies by mineral oils considered non-toxic also may have pathogenetic implications
in human autoimmune diseases.

PMID: 14718649 [PubMed – as supplied by publisher]

2: J Autoimmun.  2003 Aug;21(1):1-9.

Induction of lupus autoantibodies by adjuvants.

Satoh M, Kuroda Y, Yoshida H, Behney KM, Mizutani A, Akaogi J, Nacionales
DC, Lorenson TD, Rosenbauer RJ, Reeves WH.

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O. Box 100221, 1600 SW Archer Road, Gainesville, FL 32610-0221, USA. satohm@medicine.ufl.edu

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 TNFalpha 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.

PMID: 12892730 [PubMed – in process]

www.thewest.com.au/20040428/news/general/tw-news-general-home-sto124001.html

Thousands of flu shots thrown out

CATHY O’LEARY – MEDICAL EDITOR

Thousands of ampoules of a new influenza vaccine due to be given to elderly West Australians this winter have been dumped after freezing on a flight to Australia. About 10,000 people were due to be given the vaccine Fluad, which is believed to be more effective than standard flu vaccines and therefore better for people with lowered immunity or chronic disease. But when the manufacturer Chiron was flying the vaccine from overseas laboratories to Sydney the shipment was accidentally frozen and had to be discarded.

WA Health Department communicable diseases branch medical director Tony Watson said he had been shocked to learn about the bungle last month. He was told Chiron could not guarantee the quality of the shipment so the Therapeutic Goods Administration could not approve it for use. Fluad is an adjuvanted vaccine which means viral particles are mixed with other substances to help boost immunity and offer wider protection against disease. WA doctors who were planning to give it their patients had been told to use the standard influenza vaccine instead.

“After a lot of planning it all fell in a heap which was very disappointing but there was no way the TGA could approve it and take any risk with it,” Dr Watson said. “We were looking at providing it as part of the funded flu vaccination to selected high-risk people to gauge its acceptability in older people. The vaccine has been in use in Europe for five or six years and uses an oil-based adjuvant instead of an aluminium-based one.

“This means it produces more antibodies and provides protection for longer so is a stronger boost to the immune system. But the trade-off is that it can cause more reaction at the injection site.” Dr Watson said it was too late to get extra stock of Fluad sent to Australia in time for the winter flu season. There was no guarantee the vaccine would be funded next season when a national tender would be called for flu vaccines.

Yesterday,Health Minister Jim McGinty launched this year’s winter flu campaign, urging people aged over 65 and those with chronic disease to have their flu shot. He said that last year more than 1043 people were admitted to WA hospitals for flu treatment, about 12 per cent more than the number of cases in 2002.

BL Fisher Note:

The number of American children suffering from life threatening peanut
allergies has doubled in the past five years and the number of Americans
with food allergies has risen from 6 million to 11 million. This runs
parallel with the doubling of asthma, learning disabilities, ADHD; the
tripling of diabetes and a 200 to 7,000 percent increase in autism in every
state in the U.S. during the past 20 years. As more and more vaccines are
mandated to prevent more and more infectious diseases in early childhood,
more and more Americans are stuck on sick. So the pharmaceutical industry
produces drugs and vaccines that medical doctors sell to patients to try to
“cure” the chronic illness that vaccines and suppression of all infectious
disease helped to cause in the first place. What a racket.

http://www.mercurynews.com/mld/mercurynews/news/local/10162659.htm
San Jose Mercury News
Posted on Fri, Nov. 12, 2004

Food allergy vaccine promising
REACTIONS TO PEANUTS, WHEAT, MILK CURBED IN DOGS
By Esther Landhuis
Mercury News

It won’t keep you from catching chickenpox, but a new vaccine developed by a Stanford-led research team could one day enable millions of food allergy sufferers to fearlessly bite into a peanut butter sandwich. Tested in dogs thus far, the vaccine curbs allergic reactions to peanuts, milk and wheat.

“What we’re trying to create is an immune response that protects against allergies,” said Dr. Dale Umetsu, the study’s lead investigator and chief of the division of allergy and immunology at Lucile Salter Packard Children’s Hospital at Stanford. His group describes its canine vaccines — the first to block food allergies in an animal larger and more complex than a mouse — in a paper published online today in the journal Allergy. The dogs in the study didn’t start off with food allergies; the scientists manipulated their immune systems to mimic a human allergic response. Before getting vaccinated, the dogs could barely eat one peanut before breaking out in a skin rash. But 10 weeks after immunization, the animals devoured, on average, more than 37 peanuts before developing symptoms.

Single vaccination

Similar skin tests showed that milk-allergic dogs were able to take in 50 times more cow’s milk after getting vaccinated. Unlike today’s allergy shots — which work only on airborne allergens, such as pollen, and generally require a booster every few weeks — a single vaccination was able to stave off food allergies in the dogs for at least three months. “We’re finally entering a realm where different treatment approaches for food allergy are being developed and really look like they’re on the five- to 10-year horizon,” said Dr. Robert Wood, a pediatric allergist at the Johns Hopkins Children’s Center.

The Stanford work — a joint effort with University of California scientists at Berkeley, San Francisco and Davis — comes during an unprecedented rise in food allergies. In the past five years, peanut allergies in U.S. kids have doubled, and the number of Americans with food allergies has grown from 6 million to 11 million.

This troubling trend echoes a wider pattern. Since the 1980s, asthma and allergy rates have risen sharply in industrialized nations, where better sanitation has spurred a severe drop in infectious diseases. Dubbed the “hygiene hypothesis,” some scientists speculate that the two events are related and that certain infections may rev up the immune system in a way that protects against allergies and asthma, Umetsu said.

This idea led him to mix into his food allergy vaccines a secret ingredient — dead bacteria — hoping to trick the immune cells into responding as they would against a routine pathogen. The end goal is different, though. Most vaccines aim to boost the immune system so it can destroy the pathogen. However, food allergy vaccines are designed to spur an immune reaction that suppresses the overblown physiological responses of allergic individuals. Before the dog vaccines can be tested in people, the Food and Drug Administration requires additional experiments to test the vaccine’s toxicity.

Food allergy sufferers are eager for relief. Oakland freelance writer Claudia Perry has a 5-year-old son whose peanut allergy is severe enough to trigger life-threatening anaphylaxis. “It’s something that’s really hard to live with,” Perry said. “It’s really scary that you have to be within 20 minutes of an emergency room. We’re all hoping that the researchers find something.”

Contact Esther Landhuis at elandhuis@mercurynews.com or (408) 920-5458.

From Dorlands medical dictionary….

“Parenteral administration” includes subcutaneous injections, submucosal injections, intravenous injections, intramuscular injections, intrasternal injections, and infusion. Injectable preparations (e.g., sterile injectable aqueous or oleaginous suspensions) can be formulated according to the known art using suitable excipients, such as vehicles, solvents, dispersing, wetting agents, emulsifying agents, and/or suspending agents. These typically include, for example, water, saline, dextrose, glycerol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, benzyl alcohol, 1,3-butanediol, Ringer’s solution, isotonic sodium chloride solution, bland fixed oils (e.g., synthetic mono- or diglycerides), fatty acids (e.g., oleic acid), dimethyl acetamide, surfactants (e.g., ionic and non-ionic detergents), propylene glycol, and/or polyethylene glycols. Excipients also may include small amounts of other auxiliary substances, such as pH buffering agents.

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