[0002] The present invention is generally in the area of controlled delivery of antigens for use in vaccination or induction of tolerance to allergens, and in particular relates to cellular delivery of proteins and polypeptides.
[0006] Current treatments for allergies involve attempts to “vaccinate” a sensitive individual against a particular allergen by periodically injecting or treating the individual with a crude suspension of the raw allergen. The goal, through controlled administration of known amounts of antigen, is to modulate the IgE response mounted in the individual. If the therapy is successful, the individual's IgE response is diminished, or can even disappear. However, the therapy requires several rounds of vaccination, over an extended time period (3-5 years), and very often does not produce the desired results. Moreover, certain individuals suffer anaphylactic reactions to the vaccines, despite their intentional, controlled administration.
[0077] Adjuvants that are known to stimulate Th2 responses are preferably avoided.
[0086] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.
http://www.freepatentsonline.com/y2003/0035810.html
In 2007, FAAN began funding a study to develop another form of the peanut "vaccine." This study is investigating whether an effective peanut allergy vaccine can be designed to target specific immune cells that play a role in peanut allergy. [Ain't this nice?! Instead of preventing food allergy, let's kill the immune system cells.... -bfg]
The initial results of this study were presented at AAAAI; the scientists have shown that the early form of this vaccine is targeting the correct cells.
http://www.foodallergy.org/Research/program_update.html
But because even a small amount of peanuts can prove deadly, the scientists had to modify peanut proteins in the vaccine -- a major hurdle that took years to prefect.
"We've actually taken those allergenic portions out of it, so that's what we'll use for the vaccine, it's like a hypoallergenic peanut product," Burks said.
http://www.wyff4.com/health/4891243/detail.html
A team of scientists from across Europe are embarking on new research to develop a treatment for food allergy. "Food allergy affects around 10 million EU citizens and there is no cure," says Dr Clare Mills of the Institute of Food Research, a lead partner in the Food Allergy Specific Therapy (FAST) research project. "All people with food allergy can do is avoid the foods to which they are allergic. The threat of severe anaphylaxis has a great impact on their quality of life."
Attempted treatment with allergen-specific immunotherapy, where a patient received monthly injections with an allergen extract for three to five years, failed because it could cause anaphylaxis as a side effect...
In the FAST project, scientists will use modified variants of allergic proteins that are hypoallergenic and therefore safer. The proteins will be purified making them more effective and making it easier to control the dose.
Ninety percent of all food allergies are caused by about 10 foods. Allergies to fish and fruit are among the most common in Europe. In fish allergy the protein responsible is parvalbumin and in fruit it is lipid transfer protein (LTP). Modified hypo-allergenic versions of these proteins will be produced at tested as potential treatments.
http://www.dietaryfiberfood.com/nutrition/food-allergy-vaccine-treatment.php
Gerald Gleich, MD, University of Utah School of Medicine, Salt Lake City A T cell vaccine for shrimp allergy, 2008-
Allergy shots are an effective treatment for people who suffer from environmental allergies, such as hay fever. Gradual exposure to the allergen makes the immune system less sensitive to it. But this kind of therapy cannot be given to people with food allergies, since exposure could trigger an anaphylactic reaction. Dr. Gleich is working on a vaccine that would be safe to administer to people with shrimp allergy. The basis for the vaccine would be a T cell epitope— a tiny fragment of the allergen that would not harm people with the allergy. This method has been used successfully to develop a vaccine against cat allergy. Dr. Gleich’s first step is to identify the T cell epitope by studying white blood cells taken from people with severe shrimp allergy. He will then test the vaccine on people with shrimp allergy.
http://www.faiusa.org/?page_ID=BF1AFA97-A05F-7289-D3C863B51603015A
At the 60th Anniversary Meeting of the AAAA&I held in Denver, Colo. March 7-12, 2003, Dr Leung presented the results of the first study on the Effect of Anti-IgE Therapy in Patients with Peanut Allergy..coincidingly published in the March 13th, 2003 New England Journal of Medicine. A double-blind, randomized, dose-ranging trial was conducted in 84 patients with a history of immediate hypersensitivity to peanut. Three different doses (150, 300 or 450 mg of TNX-901)were given to randomly assigned groups every four weeks for four doses. The patients underwent a final oral challenge within two to four weeks after the fourth injection of the vaccine.
Results and conclusions: A 450 mg dose of TX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.
The authors conclude that "although these results are highly encouraging, TNX-901 is still an experimental drug, and approval for general use will require confirmation of these results in additional studies."170 (posted Mar 28th, 2003)
-Comments from Drs RA Nicklas, and BA Chowdhury, Division of Pulmonary, Allergy and Drug Products, US Food and Drug Administration, published as a guest editorial in Annals of Allergy, Asthma and Immunology, entitled Effect of anti-IgE therapy in patients with food allergy include the following:
-"....the study contains several important potential biases....which could lead to false expectations on the part of both physicians and patients.
-Two patients with negative food challenges were entered in the study.
-Open challenges were used, which automatically introduces bias, both on the part of patients and investigators.
-The fact that 3 of the investigators were not blinded to the study results enters further bias into the study. -There is concern that physicians will conclude from these data that TNX-901 may offer protection for all patients. In fact, 76% of patients were not protected against a reaction after ingestion of 8 g. of peanut flour (equivalent to 24 peanuts), and approximately 25% were not protected after ingesting as low a dose as 0.5 g of peanut flour (approx. equal to 1.5 peanuts), despite being pretreated with the highest dose of TNX-901.
-Even if it is expected that TNX-901 has a beneficial effect...it cannot be expected to protect every patient sensitized to peanut from an anaphylactic reaction after ingestion of even small amounts of peanut allergen...Unless those patients who are not sufficiently protected can be identified, physicians will have to assume that all patients are at risk and will still need to carry injectable epinephrine as well as assiduously avoid exposure to food allergens to which they are sensitized. (posted Nov 8th, 2003)