Maternal colostral leukocytes appear to enhance cell-mediated recall response, but inhibit humoral recall response in prime-boost vaccinated calves.

Whether colostral leukocytes (CLs) of vaccinated dams influence the immune response of neonatal calves following vaccination against the same antigen as their respective dams remains unanswered. Therefore, we compared the induction of humoral and cellular immune responses after vaccination in calves that had received CL-free or maternal CL-enriched colostrum from a cell-free colostrum bank of nonvaccinated cows. Also, vaccinated calves that had received fresh maternal colostrum from their own dam were included in the study. Moreover, we analyzed whether the post-partum time of priming vaccination (day 2, 5 or 10) of the calves could influence the outcome of the immune responses. All calves received a booster vaccination 23 days after the priming vaccination. All calves showed only an increase in tetanus toxoid (TT)-specific antibodies and TT-induced proliferation after booster vaccination. Tetanus toxoid-specific antibody responses in calves increased immediately after booster vaccination, irrespective of whether or not their cell-free bank colostrum had been enriched with CLs from their own dam. Conversely, calves receiving their own plain dam colostrum displayed a later humoral response, due to colostral antibodies. After booster vaccination, calves of the CL-enriched colostrum group had a more pronounced antigen-specific proliferative response than the calves of the CL-free colostrum group. We propose that CLs might have a suppressive influence on the emergence of the TT-specific antibodies, but an enhancing effect on the TT-specific lymphocyte proliferation of newborn calves upon TT vaccination, which is dependent on the time point of the priming vaccination.

Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity.

Tuberculosis, aggravated by drug-resistant strains and HIV co-infection of the causative agent Mycobacterium tuberculosis, is a global problem that affects millions of people. With essential immunoregulatory roles, phosphatidylinositol mannosides are among the cell-envelope components critical to the pathogenesis and survival of M. tuberculosis inside its host. Here we report the first synthesis of the highly complex tetraacylated phosphatidylinositol hexamannoside (Ac2PIM6), having stearic and tuberculostearic acids as lipid components. Our effort makes use of stereoelectronic and steric effects to control the regioselective and stereoselective outcomes and minimize the synthetic steps, particularly in the key desymmetrization and functionalization of myo-inositol. A short synthesis of tuberculostearic acid in six steps from the Roche ester is also described. Mice exposed to the synthesized Ac2PIM6 exhibit increased production of interleukin-4 and interferon-γ, and the corresponding adjuvant effect is shown by the induction of ovalbumin- and tetanus toxoid-specific antibodies.

Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines.

Effect of Spirulina (Arthrospira) supplementation on the immune response to tetanus toxoid vaccination in a mouse model.

The aim of this study was to investigate whether Spirulina (Arthrospira) supplementation could enhance the immune response to tetanus toxoid (TT) vaccine in a mouse model. Vaccination of TT was performed on day 7 and 21 in mice fed daily with Spirulina (50 and 150 mg/kg body weight). Both Spirulina supplementation and TT vaccination did not significantly affect body weight gain of the mice. Supplementation of Spirulina significantly enhanced IgG level (p = .01) after the first but not after the second TT vaccination. The anti-TT IgG levels of the groups that received low dose and high dose of Spirulina were not significantly different. Spirulina supplementation did not show significant effects on in vitro splenocyte proliferation and cytokine (IFN-γ and IL-4) production induced by Con A and TT. This study showed that Spirulina supplementation could enhance primary immune response in terms of antibody production, but not secondary immune response following TT vaccination in a mouse model.

Vaccines and changes in coagulation parameters in adults on chronic warfarin therapy: a cohort study.

PURPOSE: Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus and diphtheria toxoid vaccines, and persons on warfarin therapy may also receive Hepatitis A vaccine. There has been concern that vaccinations could potentially alter coagulation parameters in patients on warfarin therapy. We sought to determine whether vaccinations are associated with changes in International Normalized Ratio (INR) in persons on long-term warfarin therapy. METHODS: We conducted a retrospective cohort study of 5167 members of Group Health, a health maintenance organization (HMO) in western Washington State, who were aged 18 years and older and who were on stable long-term warfarin therapy between 1 January 1992 and 31 December 2003. We made within-person comparisons between mean INR values in the 28 days after receipt of influenza, pneumococcal, tetanus, or hepatitis A vaccine versus mean INR values during other times. RESULTS: Receipt of influenza vaccine was not associated with a change in INR value (mean change, 0.01; 95% confidence interval (CI) -0.01 to 0.03); similar results were observed for pneumococcal (mean change 0.01; 95%CI -0.07 to 0.09), tetanus (mean change 0.03; 95%CI -0.03 to 0.10), and hepatitis A vaccines (mean change 0.03; 95%CI -0.10 to 0.14). CONCLUSIONS: Our results do not suggest that vaccinations lead to clinically significant alterations in coagulation measures among adults on chronic warfarin therapy.

Effects of probiotic supplementation for the first 6 months of life on allergen- and vaccine-specific immune responses.

BACKGROUND: A reduction in microbial burden during infancy when allergen-specific memory is evolving has become a prominent explanation for the allergy epidemic. OBJECTIVE: We sought to determine whether probiotic dietary supplementation in the first 6 months of life could modify allergen- and vaccine-specific immune responses. METHODS: Two hundred and thirty-one pregnant women with a history of allergic disease and positive allergen skin prick test (SPT) were recruited into a randomized-controlled trial. The infants received either a probiotic (3 x 10(9)Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life, given independent of feeding methods. One hundred and seventy-eight children completed the study; blood samples were available from 60 children in the placebo group and 58 children in the probiotic group. Infant cytokine (IL-5, IL-6, IL-10, IL-13, TNF-alpha or TGF-beta) responses to tetanus toxoid (TT), house dust mite (HDM), ovalbumin (OVA), beta-lactoglobulin (BLG), Staphylococcus enterotoxin B (SEB) and phytohaemaglutinin (PHA) were measured at 6 months of age. RESULTS: Children who received the probiotics showed reduced production of IL-5 and TGF-beta in response to polyclonal (SEB) stimulation (P=0.044 and 0.015, respectively). They also demonstrated significantly lower IL-10 responses to TT vaccine antigen compared with the placebo group (P=0.03), and this was not due to any differences in vaccination. However, there were no significant effects of probiotics on either Type 1 (Th1) or Type 2 (Th2) T helper cell responses to allergens or other stimuli. The only other effects observed were for reduced TNF-alpha and IL-10 responsiveness to HDM allergens in children receiving probiotics (P=0.046 and 0.014, respectively). CONCLUSIONS: In summary, although we did not see any consistent effects on allergen-specific responses, our study suggests that probiotics may have immunomodulatory effects on vaccine responses. The significance and clinical relevance of this need to be determined in further studies.

Age- and sex-determined differences in the establishment of tetanus antitoxin production in guinea-pigs.

For lack of relevant data of the literature, the tetanus immunisation results obtained in the two sexes were compared in an animal model. Complete immunisation series of weaned, adult and aged guinea-pigs (20-25 animals/group) were performed with aluminium phosphate (AlPO4) adsorbed purified tetanus toxoid (PTAP) as well as with typhoid-tetanus vaccine (TY-TE) containing lipopolysaccharide (LPS). Both vaccines contained 5.0 Lf (limes flocculans, Ramon) per single dose of tetanus toxoid, purity degree: 1500 Lf/mg protein nitrogen (PN). Tetanus antitoxin titres (TAT) were measured after the first shot, and subsequently before and after booster. Compared to TAT of male animals, significantly lower titres were found in female animals after basic immunisation with PTAP in all the three age groups: 1.03 vs. 0.57, 8.75 vs. 5.64, and 0.27 vs. 0.15 IU (international units, related to the Copenhagen International Standard) per ml (sex-chromosome-dependent differences?), as well as in adult animals immunised with TY-TE, before booster: 0.07 vs. 0.02 IU/ml (hormone-dependent differences?). In the latter case the TAT results after booster were 14.49 vs. 12.89 IU/ml. Thus, the lower female prebooster titres were counterbalanced by a quick and effective increase of titres following booster. These results are in accordance with our previous observations in humans (Réthy and Réthy, 1986). From our observations with tetanus immunisation series on guinea-pigs it can be concluded that TAT may be influenced by the effects of sex chromosomes as well as of sexual hormones. During active anti-tetanus immunisation with LPS-containing vaccine (TY-TE) the lower adult female prebooster titres are presumably counterbalanced by the better functionality of the female immune memory.

[Cell activation in the hypothalamus after exposure to an antigen (based on c-fos gene expression)]. / Aktivatsiia kletok gipotalamusa posle antigennogo vozdeistviia (po ékspressii gena c-fos).

Increase of the c-fos mRNA positive cells number was insignificant in 30 min. following activation of the rat hypothalamic structures with the tetanus toxoid (TT). Elevation of the c-fos mRNA positive cells number occurred in the hypothalamic' posterior (PHA), lateral (LHA), anterior (AHA), areas dorsomedial (DMH), and ventromedial (VMH) nuclei within 2 hours of the TT administration. In 6 hours the c-fos mRNA positive cells number decreased in PHA, LHA, DMH. The c-fos mRNA expression was stable in arquate and supraoptic hypothalamic nuclei following either the TT or saline administration.

Tetanus toxoid stimulation of the hypothalamic-pituitary-adrenal axis correlates inversely with the increase in tetanus toxoid antibody titers.

In humans, endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, and the resulting increase in cortisol modulates the immune response. There is little information on the HPA axis response to other antigens. We examined the effect of the protein antigen tetanus toxoid on HPA axis activity in 10 healthy, premenopausal women (aged 28.6 +/- 2.6 yr). Subjects received im injections of placebo and tetanus toxoid at 1600 h on consecutive days. Blood samples for ACTH and cortisol were obtained every half-hour from--1 to 6 h and at 8, 12, and 16 h after each injection. Compared to placebo, tetanus toxoid administration stimulated significant increases in plasma ACTH and serum cortisol, with the maximum cortisol increase of 1.6-fold occurring 4.5 h after drug administration. Urinary free cortisol increased 1.8-fold in the 8 h after tetanus toxoid administration compared to that after placebo administration. Additionally, there was a significant inverse correlation (r = 0.87; P < 0.005) between the tetanus toxoid-induced increase in serum cortisol and the increase in tetanus antibody levels measured 1 month postvaccination. Thus, administration of the protein antigen tetanus toxoid activated the HPA axis in healthy, premenopausal women. This activation of the HPA axis correlated inversely with the antibody response to tetanus toxoid.

Rhinovirus inhibits antigen-specific T cell proliferation through an intercellular adhesion molecule-1-dependent mechanism.

To determine whether binding of human rhinovirus (HRV) to intracellular adhesion molecule-1 might disrupt airway immune processes, effects of a major HRV group, HRV-16, on T cell proliferation and cytotoxicity were defined. HRV (1-10 TCID50/cell) significantly inhibited T cell proliferation induced by antigen but not proliferation secondary to mitogens, interleukin-2, or an irradiated allogeneic T cell line. Noninfectious (UV-irradiated) HRV had similar effects. Inhibition of T cell proliferation was dependent on HRV binding to intercellular adhesion molecule-1 on monocytes, indicating that the virus interferes with lymphocyte activation indirectly through effects on antigen-presenting cells. In addition, HRV inhibited T cell cytotoxic responses but not NK cell activity. If these effects also occur in vivo, the resulting disturbance in local airway immunity could increase the chances of successful viral replication, and might also be a factor in the pathogenesis of secondary viral or bacterial respiratory tract infections.

Adjuvanticity of aluminium hydroxide and calcium phosphate in diphtheria-tetanus vaccines--I.

The potencies of two diphtheria-tetanus vaccines (DT) adsorbed to either aluminium hydroxide or calcium phosphate were compared in mice and guinea pigs. The vaccines were made from the same batches of purified toxoids and contained the same amounts of antigens. Immunizations were done once or twice with different doses of vaccine injected undiluted, diluted in saline or diluted in the corresponding adjuvant. The various potency assays showed that the adjuvanticity of calcium phosphate was lower than or equal to aluminium hydroxide. Despite the range of potency assays done, none of the methods reflected the efficacy of these vaccines in revaccination of humans. A simplified potency assay is suggested for release of final vaccine formulations to reduce the number of animals in quality control.

Lymphocyte responsiveness of children supplemented with vitamin A and zinc.

We sought to determine the effect of supplementation with zinc, vitamin A, or a combination of the two on proliferation of T lymphocytes to concanavalin A (ConA), tetanus toxoid (TT), or tuberculin (PPD) of children living in a region endemic for suboptimal vitamin A and zinc intake. The children (n = 140, aged 6-13 y) were randomly assigned and supplemented with either zinc (25 mg/d), vitamin A (1500 mg RE/d), zinc + vitamin A, or placebo for 6 mo. After a baseline blood collection, subjects were boosted with diphtheria-tetanus antigen. Proliferative responsiveness of T lymphocytes to ConA and TT in each treatment group (n = 35) was not different at baseline or postsupplementation. Children supplemented with zinc + vitamin A tended to show higher proliferative responsiveness of T lymphocytes to PPD than did those treated with placebo (P = 0.08). This tendency was observed in females but not in males. Increased zinc and vitamin A intake could result in health benefits for children living in regions endemic for suboptimal micronutrient nutriture.