Hyperimmunization

HYPERIMMUNIZATION, a method of intensified, repeated, and prolonged immunization, used exclusively in animals for the purpose of obtaining from them highly active therapeutic-prophylactic or diagnostic sera. The method of hyperimmunization rests on the general theoretical foundations of immunobiology, confirmed by experiments, that upon the artificial introduction into an animal organism in one form or another of antigens (see)—bacterial cultures, toxins, extracts, and protein substances in general—protective bodies, or antibodies (see), are formed within it after certain periods, which are concentrated mainly in the blood serum of the hyperimmunized animal. For the preparation of diagnostic sera (hemolytic, agglutinating, and precipitating), rabbits are the most suitable among small laboratory animals; sera obtained from guinea pigs, rats, and mice generally have only a low titer. Among large animals, for the purpose of obtaining large quantities of precipitating anthrax serum, used in performing the Ascoli-Valenti reaction (see Ascoli-Valenti reaction), donkeys, foals, and young horses are hyperimmunized. Likewise, for obtaining therapeutic-prophylactic sera for medical and veterinary needs, it is preferable to hyperimmunize young (4–5 years old), strong, thin-skinned horses, previously tested by veterinary supervision for glanders and tuberculosis. To obtain anti-foot-and-mouth disease and anti-plague sera for cattle, only cattle are hyperimmunized; anti-plague serum for pigs is obtained exclusively from pigs. For obtaining therapeutic-prophylactic sera, the material for repeated injections can be live and killed cultures, toxins (see), attenuated toxins (see Anatoxin), and mixtures of toxins with antitoxins (see). In view of the constant threat of losing the animal being prepared, specific schemes of hyperimmunization have been developed, and specifically distinct ones for obtaining various sera, in strict dependence both on the biological properties of the pathogen and on the sensitivity of the animal to the injected antigen. The general principle of preparing the animal is based on the fact that an organism, prepared initially with a small dose of virus or toxin, usually after 10–14 days, already tolerates more significant doses of the same antigen well. Thus, injections can follow one after another repeatedly, at certain intervals, with gradually increasing doses of the virus; in this process, the animal's organism reacts to the injections with an increase in temperature, local inflammation, general malaise, and then with the production of protective antibodies; the quantity of the latter increases with each new introduction of the antigen. The method of introducing the antigen also plays a role both in terms of safety for the animal's life and in terms of achieving the goal of obtaining a highly active serum. Thus, for obtaining antitoxic sera (anti-diphtheria, anti-tetanus), the toxin is introduced subcutaneously; for the manufacture of anti-dysentery serum, however, the toxin is injected under the skin, and the cultures (killed) are injected into a vein. The intravenous method of introducing the antigen yields a minimum of complications in the manufacture of serum against swine erysipelas, while cutaneous and subcutaneous methods of introducing the antigen are used in obtaining anti-anthrax serum. Of particular interest is the method of hyperimmunization with attenuated or detoxified antigens. For the purpose of attenuating tetanus toxin (the most dangerous antigen), the use of Lugol's solution, iodine trichloride, carbon disulfide, or formalin to treat it has long been introduced, or a combination of toxin with anti-tetanus serum is used for injection; regarding the attenuation of other toxins (diphtheria, gas gangrene, botulism, etc.), formaldehyde has gained wide application. By the mentioned methods, it is possible, without destroying the immunizing power of the toxins, to detoxify or strongly attenuate their toxic properties. Thanks to the introduction into practice of immunization with anatoxins, at the present time, the method of preliminary, repeated immunization of animals with a mixture of specific serum and the corresponding toxin has lost its significance. Depending on the biological and virulent properties of the pathogen, for the manufacture of antibacterial sera, the hyperimmunization of animals is conducted with either live or killed cultures. To obtain active anti-anthrax or anti-erysipelas serum for pigs, it is necessary to inject the most viable virulent cultures; conversely, for obtaining anti-typhoid, anti-cholera, or anti-paratyphoid sera, hyperimmunization can also be conducted with killed cultures. Besides the generally accepted, generally slow method of preparing the animal, there exists a so-called intensive, forced method of hyperimmunization. It is practiced mainly in veterinary medicine in the manufacture of anti-plague (for cattle), anti-anthrax, and anti-erysipelas (for pigs) sera; with this method, the intermediate periods between antigen injections are reduced to a minimum (to 2–3 days), while, however, conforming to the completion (after injection) of the organic and temperature reaction.