Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is inorganic
Reexamination Certificate
1999-09-03
2003-05-06
Chin, Christopher L. (Department: 1641)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
Carrier is inorganic
C436S501000, C436S518000, C436S506000, C436S507000, C436S513000, C436S523000, C436S529000, C436S526000, C436S532000, C436S535000, C436S811000, C436S815000, C424S130100, C424S141100, C424S142100, C424S147100, C424S154100, C424S159100, C424S160100, C424S171100, C424S275100, C424S009800, C424S009810, C424S900000, C600S306000, C600S506000, C600S012000, C530S868000
Reexamination Certificate
active
06558961
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to particle-based immunodiagnostic methods. More particularly, the invention pertains to methods for assessing immunocompetence, antibody and cell mediated immunity, antigen exposure, or allergic conditions in an individual by accelerating diagnostic particles into a target skin site in the individual.
BACKGROUND OF THE INVENTION
Allergies represent one of the most common and well characterized immune disorders in humans, affecting roughly 20 percent of all individuals in the United States. Allergic reactions are generally immune reactions that are initiated by IgE-dependent stimulation of tissue mast cells and related effector molecules (e.g., basophils). Binding events between cell surface bound IgE molecules and antigen results in rapid release of biological response modifiers which bring about increased vascular permeability. vasodilation, smooth muscle contraction and local inflammation. This sequence of events is termed immediate hypersensitivity and begins rapidly, usually within minutes of exposure in a sensitized individual to antigen. In its most severe systemic form, anaphylaxis, such immediate hypersensitivity can bring about asphyxiation, produce cardiovascular collapse, and even result in death. Individuals that are prone to strong immediate hypersensitivity responses are referred to as “atopic” and are said to suffer from “allergies.” Clinical manifestations of atopy include hay fever (rhinitis), asthma, urticaria (hives), skin irritation (e.g., chronic eczema), and related conditions.
A number of clinical test procedures for assessing allergies have been described and are known in the art. See generally American College of Physicians, “Allergy Testing,”
Ann. Intern. Med.
(1989) 110:317-320; Bousquet, J. (1988) “
In Vivo Methods for Study of Allergy: Skin Tests, Techniques, and Interpretation,
” Allergy, Principals and Practice, 3
rd
ed., Middleton et al., eds., CV Mosby Co., St. Louis, Mo., pp. 419-436; and Van Arsdel et al. (1989)
Ann. Intern. Med.
110:304-312. These so-called “skin tests” or “scratch tests” involve introduction of antigens into the epidermis via skin prick or scratch, or introduction into the dermis via intracutaneous (intradermal) injection. An immediate wheal and flare reaction at the site of introduction (the classic atopic reaction) indicates antibody-mediated (IgE) hypersensitivity to the test antigen. More particularly, when a sensitized individual is challenged by an appropriate antigen in a skin or scratch test, the site of introduction becomes red from local vasodilation. In a second phase of the reaction, soft swelling occurs (the wheal) and, in a third phase, blood vessels at the margins of the wheal dilate and become engorged with red blood cells, producing a characteristic erythemic rim (the flare). The full wheal and flare reaction usually appears within 10 to 15 minutes of antigen administration, and generally subsides within about an hour. A wheal of sufficient size with accompanying flare represents a positive test for allergy against the antigen.
A related methodology can be used to assess cell mediated immune (CMI) responses in individuals immunized against, infected with or exposed to intracellular pathogens such as bacteria, viruses, or other microbes. In like manner, these techniques can be used to diagnose and/or identify the presence of neoplastic disease in individuals. More particularly, the delivery of recall antigens to diagnose preexisting immunity against, exposure to, or infection by various pathogens is known in the art. Recall antigens are immunogenic moieties (from a pathogen) which are capable of eliciting an antigen-specific CMI response in individuals that have been exposed to, are harboring, or have been immunized against the relevant pathogen. Most commonly, the antigen-specific CMI response is a delayed type hypersensitivity (DTH) response, a form of cell-mediated immunity in which the ultimate effector cell is the activated mononuclear phagocyte (macrophage).
In a commonly employed test, a relatively small amount of soluble purified protein derivative (PPD), a protein prepared from the
Mycobacterium tuberculosis
pathogen, is delivered to an individual via intradermal injection, and will elicit a DTH response in individuals recovering from primary tuberculosis or who have been vaccinated against tuberculosis. In this test, the classic DTH response evolves over a period of about 24 to 48 hours. Infiltration of T cells and blood monocytes at the injection site causes escape of fibrinogen from blood vessels to surrounding tissue where it is converted to fibrin. Fibrin deposition and accumulation of T cells and monocytes about the injection site causes local tissue swelling and hardening (“induration”), the hallmark of DTH. Induration is generally detectable by about 18 hours after antigen injection, and is maximal at 24 to 48 hours. The presence of sufficient induration and/or erythema at the injection site represents a positive test for exposure to or vaccination against the
Mycobacterium tuberculosis
pathogen.
Similar such testing procedures can be used to assess CMI responses to other microbial antigens, where detection of a suitable DTH response to a delivered antigen is used as an alternative to, or in conjunction with standard immunological methods of testing for serum antibody titers or serum antigen levels. These methods can also be used to assess neoplastic conditions, where the recall antigen is from a known tumor-associated antigen, and a positive test is indicative of the presence of neoplasia in the individual.
Such delayed type hypersensitivity testing can also be used to evaluate individuals suspected of having primary or acquired immune deficiency disorders in which cell-mediated immunity is decreased or absent. Turk, J. L. (1980)
Delayed Hypersensitivity,
in “Research Monographs in Immunology,” Vol. 1, Elsevier/North Holland Biomedical Press, New York, N.Y. pp. 111-157. In this regard, loss of DTH responses to universally encountered antigens (e.g., candidal antigens) is indicative of T cell function deficiency, a clinical condition commonly termed “anergy.” Anergic individuals are extremely susceptible to infection by microorganisms normally resisted by cellular immunity. Anergy, as shown by reduced or loss of DTH to one or more common antigens, has been used to assess malnutrition (Law et al. (1973)
Ann. Intern. Med.
79:545-550), and depressed DTH responses can be used to assets conditions such as diabetes mellitus, uremia, and certain acquired immune deficiency disorders (Spitler et al. (1976)
Manual of Clinical Immunology,
Rose et al. Eds, A.S.M., Washington, D.C., pp53-63). Positive correlation between defective cell-mediated immunity and disseminated cancer, again as indicated by anergy to multiple skin test antigens, has also been reported. Johnson et al. (1979)
Amer. J. Surgery
137:536-541; Lamb et al. (1962)
J. Immunol.
89:555-558; Eilber et al. (1970)
Cancer
25:362-367; Hersh et al. (1971)
N. Engl. J. Med.
285:1211-1216; and Fass et al. (1970)
N. Engl. J. Med.
282:776-780.
SUMMARY OF THE INVENTION
It is a primary object of the invention to provide methods for reliably and reproducibly assessing allergies, conditions of humoral and cellular immunity, conditions of anergy, and neoplasia in individuals using particle delivery methods to deliver antigens or allergens to target skin sites in an individual.
In one aspect of the invention, a method is provided for assessing a localized skin immune reaction against a selected agent in an individual. The method entails preparing particles which comprise an immunogenic moiety (e.g., an antigen) from the selected agent. The particles are accelerated into a target skin site in the individual, and the visual appearance of the target site is then assessed to determine the presence or absence of a skin reaction at or about the site of administration, wherein presence of the skin reaction is indicative of a humoral or cellular immune response against the selected a
Fuller Deborah L.
Roberts Lee K.
Sarphie David F.
Chin Christopher L.
Do Pensee T.
McCracken Thomas P.
PowderJect Research Limited
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