Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge.

The protective efficacy of oral bovine immunoglobulin concentrates derived from colostrum against challenge with Shigella flexneri was studied in healthy adult volunteers in a randomized, double-blind fashion. Volunteers were given a product consisting of hyperimmune immunoglobulin concentrate with a high titer of anti-S. flexneri 2a lipopolysaccharide (LPS) with sodium bicarbonate or a control preparation with sodium bicarbonate three times a day for seven days. On the third day of treatment, volunteers received a challenge of 10(3) colony-forming units of S. flexneri 2a strain 2457T. None of the volunteers who received the high-titered hyperimmune product became ill, compared with 45% of volunteers who received the placebo (P less than 0.05). The duration of shedding of the challenge organism was decreased, and the active immune responses to S. flexneri LPS were less frequent and of lower magnitude in volunteers given the immunoglobulin concentrate than in those in the control group. High-titered, orally administered bovine immunoglobulin concentrate protects against shigellosis and may be useful in preventing shigellosis among travelers, military personnel, and individuals at risk during a Shigella outbreak.

Immunoglobulins in milk from cows immunized with oral strains of Actinomyces, Prevotella, Porphyromonas, and Fusobacterium.

Immunization of pregnant cows with bacteria leads to the presence of high concentrations of specific antibodies in colostrum and milk. A total of 14 cows was immunized with single strains of heat-killed oral bacteria or pools of strains of Actinomyces, Porphyromonas, Prevotella, and Fusobacterium. Two cows were treated with adjuvant alone. The mean percentages of IgG1, IgG2, IgM, and IgA in all of the milks were 83.8, 3.8, 9.3, and 3.1, respectively. ELISA and whole cell agglutination assays demonstrated high titers in the milks from the cows immunized with either individual strains or the bacterial pools. The highest titers determined by ELISA belonged to the IgG1 isotype and in several milks were 64-fold greater than titers in milk from cows treated with adjuvant alone. The concentrations of all antibodies and the titers determined by ELISA and whole cell agglutination assays markedly decreased from the first to the sixth milkings. The functional specificity of the antibodies was demonstrated by agglutination tests against a wide range of bacteria including members of Actinomyces, Fusobacterium, Porphyromonas, Prevotella, Streptococcus, Eubacterium, Propionibacterium, Peptostreptococcus, Bacteroides, Actinobacillus, Haemophilus, Capnocytophaga, and Wolinella. Minimal cross-reactions with bacteria in other genera were observed with all of the milks. High-titer milk preparations have been obtained from immunized cows, and the capacity of the bovine antibodies to agglutinate target bacteria indicates their potential usefulness in oral passive immunization studies.

Nonspecific antibacterial factors in milk from cows immunized with human oral bacterial pathogens.

Both the immunoglobulins and non-specific antibacterial factors in milk from cows immunized with pathogenic oral bacteria have the potential to influence the oral microflora during passive immunization studies. The first six milks after calving were collected from 2 cows immunized with adjuvant and from 14 cows immunized with adjuvant and heat-killed strains of periodontopathic Actinomyces, Porphyromonas, Prevotella, and Fusobacterium. Analysis of the products from the first to the sixth milks revealed that the protein and lysozyme content decreased approximately 66 and 72%, respectively; the mean specific activity of the enzyme remained relatively constant. In contrast, the mean lactoperoxidase activity increased 2.3-fold in the second milking and increased further in the fourth and sixth milkings. The mean iron-binding activity increased 1.2-fold from the first to the second milkings and then decreased 3.6-fold through the sixth milking. Cows immunized with adjuvant alone showed similar responses. Per unit volume, the milk contained approximately 150 times less lysozyme than whole human saliva obtained from six subjects but higher concentrations of lactoperoxidase and iron-binding components. Purified bovine nonspecific factors prevented the growth of the bacteria used for immunization when bacteria were tested at concentrations similar to those found in saliva and milk. Because bovine nonspecific antibacterial factors could influence both the pathogenic target bacteria and the indigenous microflora in oral passive immunization studies with bovine immunoglobulins, the presence of these proteins should be considered.

Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate.

Gestating Holstein cows were vaccinated with Clostridium difficile toxoid prepared from the culture filtrate of a strain that produces high levels of toxins A and B and other antigens. A bovine immunoglobulin G (IgG) concentrate was prepared from colostrum collected at parturition. The results of our studies showed that hamsters treated prophylactically with the hyperimmune bovine IgG concentrate were protected against C. difficile disease. These results suggest that orally administered hyperimmune bovine IgG specific for C. difficile culture filtrate may be useful in prophylaxis against C. difficile disease.

Nonendemic adult T-cell leukemia/lymphoma in the United States: report of two cases and review of the literature.

Adult T-cell leukemia/lymphoma (ATLL) is a recently described distinct clinicopathologic entity characterized by a leukemic or lymphomatous proliferation of hyperlobulated peripheral T-cells, which is usually widespread at presentation and is associated with infection by a type C retrovirus. ATLL rarely is described outside of endemic regions, which include southwestern Japan, the Caribbean region, and the southeastern United States. The authors report the clinical, pathologic, and immunologic features of two cases of nonendemic ATLL that occurred in patients from the midwest United States. One patient was a 16-year-old white girl from rural Iowa, and the other was a 46-year-old white man from rural Minnesota. The features of 13 other probable nonendemic ATLL cases from the United States were compiled and reviewed. In the United States, nonendemic ATLL occurred in widespread geographic locations, affected mostly white people, and was characterized by an aggressive course with generalized adenopathy, blood and bone marrow involvement, and hepatosplenomegaly at presentation. Skin involvement was present in one-fourth of the patients. Hypercalcemia was rare. Although antibodies to type C retrovirus were detected in three of the five patients tested, the available data is not sufficient to establish a conclusive association between nonendemic ATLL and type C retrovirus infection.

Destruction of antibody idiotopes with ultra-low concentrations of reducing agents.

The nature of the idiotopes present on F(ab')2 fragments prepared from rabbit anti-micrococcal carbohydrate antibodies and the loss of idiotypic reactivity of these F(ab')2 fragments upon iodination were examined. Rabbit anti-micrococcal idiotopes were shown to be exquisitely sensitive to treatment with very low concentrations of sodium metabisulfite or 2-mercaptoethanol. The treatment destroyed anti-micrococcal idiotopes, as shown by the loss of idiotopes on F(ab')2 fragments after reduction; the allotype epitopes and the antigen binding capacity of the F(ab')2 fragments were unaffected. The destruction of the idiotopes by very low concentrations of reducing agents indicated that an extremely labile disulfide bond is involved in the structure of the idiotope or in the maintenance of the conformation of the anti-micrococcal idiotopes. Identical reduction-sensitive anti-micrococcal idiotopes have been demonstrated in a number of related outbred rabbits, and in each case they induced a natural auto-anti-idiotype (AAI) antibody response. Recognition of the existence of these reduction-sensitive idiotopes and their properties could provide a basis for further study of these idiotopes and may lead to a better understanding of the idiotope network.

Properties of narrow-range ampholytes isolated from wide-range ampholyte preparations.

A simple procedure for obtaining useful narrow-pH-range ampholytes from inexpensive laboratory-synthesized ampholytes by preparative isoelectric focusing in Pevikon is described. The narrow-range ampholytes prepared in this way are comparable to commercial ampholyte preparations as judged by conductivity, buffer capacity, pH gradient formation, and resolving power. These inexpensive narrow-range ampholytes are particularly well suited to preparative isoelectric focusing applications requiring large quantities of ampholytes.

Naturally induced auto-anit-idiotypic antibodies. Induction by identical idiotopes in some members of an outbred rabbit family.

Naturally induced auto-anti-idiotypic (AAI) antibody responses specific for antimicrococcal antibody idiotypes were detected in 42% of the rabbits in a family immunized with Micrococcus lysodeikticus. The natural AAI response of each rabbit recognized only a portion (11-41%) of that individual's total antimicrococcal antibody population. Cross-reactions of idiotypes were observed within the group of rabbits exhibiting natural AAI responses. Examination of the basis for the cross-reactions showed that the natural AAI antisera recognized identical idiotopes on the antimicrococcal F(ab')2 fragments from each rabbit that made an AAI response. The cross-reactive idiotopes were shown to be of paternal origin and were found in the antimicrococcal antibodies of each offspring. The data strongly support the idiotypic network concept that naturally induced AAI responses may occur routinely in outbred normal individuals as a result of antigenic stimulation. Further, the data suggest that the induction of regulatory AAI antibody responses in outbred rabbits may depend on the expression of particular germ line idiotopes.