1. Field of the Invention
This invention relates to the use of honey and/or bee as a component of a vaccine for immunizing cows and/or chickens against the allergens and microorganisms contained therein. The invention further relates to food products such as milk and/or eggs from animals hyperimmunized against honey and/or the bee, and to the use of such food products, as a source of anti-honey factors which protect a host which ingests such food products against the allergens and microorganisms found in honey.
2. Description of the Background Art
The body of the bee, more specifically the hind legs, is used to collect pollen that is used as a food by the bees in the hive. Many of the pollens are allergens. These are the same allergens (for example, ragweed) that cause environment-related allergic reactions in humans or other animal species living in the area. As a result, honey made by the bee, and the body of the bee, carry a random sample of various pollens and other allergens or microorganisms that are indigenous to a specific geographical area. Bees and honey from different geographical areas carry different kinds of pollen because the vegetation varies.
The allergic properties of honey have been described. (Miedzobrodza, A. et al., Przegl. Lek. 34:721-724 (1977); Bonneau, J. C. et al., Allerg. Immunol. 17:526-527 (1985)). In susceptible individuals honey can induce bronchial asthma attacks, and allergic and antibody-mediated hypersensitivity reactions, such attacks may be severe and be accompanied by tissue damage.
Young infants are unusually susceptible to toxic microorganisms in honey. For a food product, honey provides an unusually concentrated source of spores of Clostridium botulinum, the microorganism responsible for botulism. Clostridium botulinum has been estimated to contaminate 10-15% of all honey. (Brown, L. W., J. Pediatr. 94:337-338 (1979); Spika, J. S. et al., Am. J. Dis. Child. 143:828-832 (1989)). Unfortunately, honey is often used as an alternative to cane sugar in infant formula preparations and infant botulism is now the most common form of botulism identified in this country.
Honey is the only food source thus far implicated in the pathogenesis of infant botulism. Approximately 15% of the infant botulism cases identified in the United States are associated with ingestion of honey (Spika, J. S. et al., Am. J. Dis. Child. 143:828-832 (1989); Hauschild, A. H. W. et al. J. Food Prot. 51:892-894 (1988)). Infant botulism may also arise due to ingestion or inhalation of the C. botulinum spores from environmental exposure to dust or dirt. When ingested, toxin is formed within the gut of the infant after the germination and multiplication of the C. botulinum spores.
Release of botulism toxin in adults and especially in infants and children can be fatal. Treatment of botulism in infants is merely supportive. Thus, it would be advantageous to have a method for the treatment or prevention of infant botulism.
It has been known in the prior art to produce milk having a variety of therapeutic effects. Beck, for example, has disclosed a milk containing antibody to Streptococcus mutans that has dental caries-inhibiting effects (Beck, U.S. Pat. No. 4,324,782; British Patent 1,505,513). The milk is obtained by hyperimmunization of a cow with Streptococcus mutans antigen and collecting the therapeutic milk therefrom. Beck has also described a milk having anti-arthritic properties (U.S. Pat. No. 4,732,757), and has patented a method of treating inflammation using milk from hyperimmunized cows (Beck, U.S. Pat. No. 4,284,623). Stolle has disclosed a method of using milk from a hyperimmunized cow to treat diseases of the vascular and pulmonary systems (Stolle et al., U.S. Pat. No. 4,636,384). Heinbach, U.S. Pat. No. 3,128,230, has disclosed milk containing alpha, beta and gamma globulins against anti-9-enic haptens. Singh (U.S. Pat. No. 3,911,108), Peterson (U.S. Pat. No. 3,376,198 and Canadian Patent 587,849), Holm (U.S. application (published) Ser. No. 628,987), Tunnah et al. (British Patent 1,211,876), and Biokema S. A. (British Patent 1,442,283) have also described antibody-containing milks.
In U.S. Pat. Nos. 4,636,384, and 4,897,265, there was disclosed a method of lowering blood lipid levels and treating lipid-associated vascular disorders, as well as treating macrophage-related pulmonary disorders, comprising feeding test animals and humans antibody-containing milk derived from cows maintained in a hyperimmune state by injections of polyvalent antigens derived from mixtures of killed bacteria. In allowed application Ser. No. 07/355,786, filed May 22, 1989, and which is a file wrapper continuation of U.S. Ser. No. 069,139, filed Jul. 2, 1987, now abandoned, there was disclosed use of antibody-containing milk derived from hyperimmunized cows for the treatment of gastrointestinal disorders.
It is well known to those skilled in the art of immunology that serum globulin fractions consisting of various antibody types such as, for example, IgA, IgG, and IgM, can be used to counter corresponding antigens, thereby neutralizing the effects of the antigens. There are an almost infinite number of harmful antigens to which animals can be exposed, including carcinogenic, bacterial, viral, and regulatory factors of plant and animal origin, as well as toxins and poisons.
Normally, upon exposure to a foreign antigen, e.g., pollen, the immune system of the host will produce antibodies that will neutralize the effects of the antigen. Exposure to such foreign antigens can occur either naturally, or deliberately by administration of the antigen in vaccine form. The latter is generally referred to as active immunization of the host species exposed to the antigen. The antibodies produced in response to such vaccination are homologous to said given species of animal, and are epitopic to the antigen.
It is known that various genera of the class Aves, such as chickens (Gallus domesticus), turkeys, and ducks, produce antibodies in their blood and in their eggs against factors which cause avian diseases, as well as against other antigens. For example, LeBacq-Verheyden et al., Immunology 27:683 (1974), and Nestle, G. A. et al., J. Med. 130:1337 (1969), have quantitatively analyzed immunoglobulins of the chicken. Polson, A. et al., Immunological Communications 9:495-514 (1980) immunized hens against several proteins and natural mixtures of proteins, and detected IgY antibodies in the yolks of the eggs. Fertel, R. et al., Biochemical and Biophysical Research Communications 102:1028-1033 (1981) immunized hens against prostaglandins and detected antibodies in the egg yolk. Jensenius et al., Journal of Immunological Methods 46:363-368 (1981), provide a method of isolating egg yolk IgG for use in immunodiagnostics. Polson et al., Immunological Communications 9:475-493 (1980), describe antibodies isolated from the yolk of hens that were immunized with a variety of plant viruses.
Polson, U.S. Pat. No. 4,357,272, discloses the isolation of antibodies from the yolks of eggs derived from hyperimmunized hens. The hyperimmunization was elicited by repetitive injections into the hens of antigens represented by plant viruses, human IgG, tetanus antitoxin, snake antivenins, and Serameba antigens. Polson, U.S. Pat. No. 4,550,019, discloses the isolation from egg yolks of antibodies raised in the hen by hyperimmunization with immunogens having a molecular or particle weight of at least 30,000. The antigens used to hyperimmunize the chickens were selected from among plant viruses, human immunoglobulins, tetanus toxin, and snake venoms.
In Ser. No. 577,804, there is disclosed a method of passive immunization of a mammal which comprises parenterally injecting a purified heterologous antibody obtained from the eggs of a domesticated fowl, which species has been immunized against an antigenic substance, and wherein the mammal has a history of consumption of eggs from such domesticated fowl. The invention disclosed in U.S. Pat. No. 4,748,018 expands on the concepts disclosed in U.S. Ser. No. 577,804, in that administration of the egg antibody can be any appropriate route, not only parenteral.
The present invention is a further development over the inventions disclosed and claimed in the aforementioned applications, the entire disclosures of which are herein incorporated by reference.