Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is one of the most widespread and devastating gastrointestinal diseases in neonates. Destruction of the intestinal barrier is the main underlying cause of NEC. The aim of this study was to determine the role of lactadherin in preventing NEC in a neonatal rat model and investigate the molecular mechanism of lactadherin-mediated protection of the intestinal barrier. Neonatal rats were divided into three groups: dam feeding (DF), NEC (NEC), and NEC supplemented with 10 µg/(g·day) recombinant human lactadherin (NEC+L). Intestinal permeability, tissue damage, and cell junction protein expression and localization were evaluated. We found that lactadherin reduced weight loss caused by NEC, reduced the incidence of NEC from 100% to 46.7%, and reduced the mean histological score for tissue damage to 1.40 compared with 2.53 in the NEC group. Intestinal permeability of lactadherin-treated rats was significantly reduced when compared with that of the NEC group. In addition, the expression levels of JAM-A, claudin 3, and E-calcium in the ileum of NEC group animals increased compared with those in the ileum of DF group animals, and these levels decreased in the NEC+L group. Lactadherin changed the localization of claudin 3, occludin, and E-cadherin in epithelial cells. The mechanism underlying lactadherin-mediated protection of the intestinal barrier might be restoring the correct expression levels and localization of tight junction and adherent junction proteins. These findings suggest a new candidate agent for the prevention of NEC in newborns.

Use of gamma-inulin/liposomes/Vitamin E adjuvant combination in contraceptive vaccines.

The adjuvanticity of two gamma inulin/liposomes/Vitamin E combinations was evaluated in the mouse, in contraceptive vaccines with sperm protein extracts or a synthetic HE2 peptide ("Human Epididymis gene product"; residues 15-28) as antigen. The HE2 peptide was not conjugated to a protein carrier, to ensure that the antibodies elicited were specific against the HE2 peptide. The adjuvant combinations were designed to increase adjuvanticity, as their components have complementary mechanisms, and their performance was compared to Freund's adjuvant. Antibody production against native sperm structures was determined in sera by ELISA immunoassay and immunohistology. Toxicity of adjuvants was determined by histopathological study and treated mice were monitored for signs of pain or distress. Our results show that the gamma inulin (1-2 microm particle size)/liposomes/Vitamin E combination, with sperm protein extracts, is better than Freund's adjuvant because it elicits good antibody titres without any toxicity. When the synthetic HE2 peptide is used as antigen, the gamma inulin (1-2 microm particle size)/liposomes/Vitamin E combination is less effective than Freund's adjuvant; nevertheless, the anti-HE2 antibodies elicited are highly specific and recognize native structures in sperm.

[The potentials for immunization against influenza using liposome-incorporated viral surface antigens]. / Possibilités d'immunisation contre la grippe à l'aide d'antigènes viraux de surface incorporés aux liposomes.

Studies were conducted using uni- and multilamellar liposomes to establish optimum conditions for influenza antigen incorporation in view of their transport to the target cells for experimental influenza prophylaxis in hybrid white mice. Radiometric determinations showed a good level of preparation purification, a good efficiency of incorporation in liposomes of the active biological material, the liposome linked radioactivity distribution among different organs. Charged liposomes induced solid and long lasting resistance against influenza control infection.

[Protective action of liposome-incorporated surface antigens of the influenza virus by different methods of immunization]. / Protektivnoe deistvie vkliuchennykh v liposomy poverkhnostnykh antigenov virusa grippa pri razlichnykh sposobakh immunizatsii.

The influence of different routes of immunization on the protective effect of liposome-incorporated influenza A/PR/8/34 virus surface antigens was studied. Influenza virus surface antigens, neuraminidase and hemagglutinin, incorporated into liposomes, were shown to have a significant protective effect upon intraperitoneal and intranasal administration against a lethal dose of influenza virus as compared with immunization using a free antigen solution against the same infection. The protective effect is poor in intravenous immunization with influenza virus antigen-containing liposomes. It is concluded that combining of influenza virus antigens with liposomes may be used for preparation of new influenza vaccines.

Vaccination of pregnant cows with K99 antigen of enterotoxigenic Escherichia coli and protection by colostrum in newborn calves.

The immune response to the K99 was tested in 45 pregnant cows, subcutaneously vaccinated, for protecting the newborn calves. Serological tests were performed in the blood sera of all animals and in the milk and colostrum sera; hemogram, inhibition of the adhesion to the brush border and histological tests were performed. The calves from vaccinated cows survived the experimental infection after the suction of colostrum in spite of the fact that the calves from control dams died with diarrhea.

Protective secretory immunoglobulin A antibodies in humans following oral immunization with Streptococcus mutans.

Ingestion of a vaccine containing killed Streptococcus mutans, originally isolated from each volunteer, daily for 10 consecutive days induced increased levels of specific secretory immunoglobulin A (sIgA) antibodies to S. mutans cells and two cell surface proteins, glucosyltransferase and surface antigen I/II, in parotid saliva and tears of four healthy males and in parotid saliva, tears, colostrum, and milk of a pregnant woman. In addition, these antibodies inhibited glucosyltransferase activity. Both IgA1 and IgA2 antibodies were induced. The levels of IgA antibodies in all secretions remained significantly above preimmunization levels for more than 50 days after oral administration of antigen. A second series of immunizations for 7 consecutive days resulted in even higher levels of sIgA antibodies, which peaked earlier and persisted longer than those observed after the primary immunizations. No increase in levels of antibodies in serum were detected in any subject. Antibodies reactive with human heart and kidney antigens could not be detected in saliva, tears, colostrum, milk, or serum samples collected at any time during the immunization regimen. The numbers of viable S. mutans organisms in dental plaque and whole saliva decreased after each series of immunizations, which correlated with increased levels of IgA antibodies in saliva, suggesting that IgA antibodies in saliva were responsible for the reduced adherence of this bacterium. These results indicate that ingested S. mutans antigen induces secretion of specific IgA1 and IgA2 antibodies in saliva, tears, colostrum, and milk, providing further evidence for the existence of a common mucosal immune system.

[Experimental study of the therapeutic action of the surface antigenic complex of Staphylococcus]. / Eksperimental'noe izuchenie lechebnogo deistviia poverkhnostnogo antigennogo kompleksa stafilokokka.

The comparative experimental study of the therapeutic action of staphylococcal antigenic complex obtained by the method of aqueous extraction, corpuscular formalinized vaccine and commercial staphylococcal preparations (native toxoid and antiphagin) revealed the statistically significant difference in the process of the healing of local dermatonecrotic inflammation in the rabbits treated with staphylococcal antigenic complex in comparison with the untreated rabbits.