Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine.

Chitosan and alginate salts are natural biopolymers that have gained recent attention in the biomedical sectors. Their properties allow them to become potential candidates as safe, cheap, and effective vaccine adjuvants. The present study aimed to enhance the immunogenic response of a current injectable killed cholera vaccine (KCV) using chitosan and alginate salt as natural adjuvants against alum. We tested KCV adjuvanted with alum, chitosan, and sodium alginate in mice. Mice were immunized intraperitoneally with KCV adjuvanted with alum, chitosan, or alginate salt and compared with a control unadjuvanted immunized group. Humoral, cellular, and functional immune responses were evaluated in all groups. The addition of adjuvants, particularly natural adjuvants, to KCV significantly improved the immune response as demonstrated by specific antibody increase, strong proliferation effects, and high protection rate against different challenge doses of cholera strains. Our findings demonstrate that chitosan and alginate salt are superior adjuvants for boosting the KCV immune response and highlights the requirement for further vaccine development.

Dietary arginine supplementation enhances immune responses to inactivated Pasteurella multocida vaccination in mice.

The present study was conducted to determine the adjuvant effect of arginine in mice immunised with inactivated vaccine. Mice immunised with an inactivated Pasteurella multocida vaccine and fed diets supplemented with 0·2 % (vaccine-0·2 %) or 0·5 % (vaccine-0·5 %) arginine exhibited 100 % protection from a challenge with P. multocida serotype A (CQ2) at a dose of 4·4 × 105 colony-forming units (2LD50; median lethal dose), when compared with mice receiving no arginine supplementation. Meanwhile, antibody titres in the vaccine-0·2 % arginine group were much higher than those in the vaccine-oil adjuvant group before challenge and at 36 h post-infection. Furthermore, immunisation with the inactivated vaccine and dietary supplementation with 0·2 % arginine increased serum levels of glutathione peroxidase, in comparison with immunisation with the inactivated vaccine and an oil adjuvant. Collectively, dietary arginine supplementation confers an immunostimulatory effect in mice immunised with the inactivated P. multocida vaccine. The present results also indicate that optimal supplemental doses of arginine are 0·2-0·5 % in the mouse model.

Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection.

BACKGROUND: Due to the rising use of nanomaterials (NMs), there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs), which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis. RESULTS: We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions. CONCLUSIONS: A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.

Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune response and development of postischemic neuronal damage.

BACKGROUND AND PURPOSE: Consumption of fish has been shown to reduce risk of coronary heart disease and, possibly, of ischemic stroke. Because docosahexaenoic acid (DHA) is the most likely neuroactive component within fish oil, we hypothesized that exposing mice to a DHA-enriched diet may reduce inflammation and protect neurons against ischemic injury. METHODS: To visualize the effects of DHA on neuroinflammation after stroke, TLR2-fluc-GFP transgenic mice were exposed to either a control diet, a diet depleted in n-3 polyunsaturated fatty acid, or a diet enriched in DHA during 3 months. Real-time biophotonic/bioluminescence imaging of the TLR2 response was performed before and after middle cerebral artery occlusion, whereas cytokines concentrations and stroke area analyses were performed at 3 and 7 days after middle cerebral artery occlusion, respectively. RESULTS: We show that a 3-month DHA treatment prevented microglial activation after ischemic injury, reduced the ischemic lesion size, and increased levels of the antiapoptotic molecule Bcl-2 in the brain. Additional analysis revealed a significant decrease in the levels of COX2 and IL-1ß, but not in other proinflammatory cytokines. Importantly, long-term DHA supplementation significantly changed the n-3:n-6 polyunsaturated fatty acid ratio in the brain. CONCLUSIONS: Collectively, these data indicate that diet-induced accumulation of DHA in the brain protects against postischemic inflammation and injury. Because DHA is widely available at low cost and has an excellent safety profile, our data suggest that increased DHA intake may provide protection against acute immune response/brain damage in ischemic stroke.

Differential effect of phosphodiesterase IV inhibitor RP73401 on various inflammatory and immune responses relevent to rheumatoid arthritis.

Phosphodiesterase (PDE) IV inhibitors have been reported to possess potent anti-inflammatory activities through enhancement of cAMP. In this study, the immunopharmacological effect of PDE IV inhibitor (RP73401) was further carefully evaluated. RP73401 strongly blocked the production of tumor necrosis factor (TNF)-alpha from lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7) and human peripheral blood mononuclear cells (PBMC) and LPS-primed mice. RP73401 did not relieve joint inflammation in adjuvant-arthritis (RA) model, whereas the compound attenuated arachidonic acid-induced inflammation. RP73401 displayed weak or no modulatory effects on the activation of macrophage and lymphocytes (assessed by proliferation, nitric oxide (NO) release and cell-cell adhesion, TNF-alpha production upon phorbol 12-myristate 13-acetate (PMA) treatment), and fluorescein-isothiocynate (FITC)-induced ear oedema. Collectively, these data suggest that PDE IV inhibitor RP73401 may differentially modulate various immune responses and these may explain its inability to inhibit adjuvant-induced joint inflammation or FITC-induced ear oedema.

Prevalence of rubella antibodies among schoolgirls in Sana'a, Republic of Yemen.

To determine the prevalence of rubella antibodies and age of exposure to rubella among Yemeni schoolgirls, we studied the sera samples of 323 female students (age range 11-21 years; mean age 16.26 +/- 1.89 years) drawn from three schools in Sana'a. All samples were screened for rubella IgG antibodies using enzyme linked immunosorbent assay and, if negative, for IgM in order to exclude the possibility of recent exposure. Of 323 sera, 296 (91.64%) were positive for rubella IgG. All IgG negative sera were also IgM negative. Comparable antibody prevalence was observed in all age groups. The prevalence of rubella IgG among Yemeni schoolgirls is high, with most becoming immune between the ages of 11 and 21 years. Although the age of exposure seems to be < or = 13 years, further investigation is needed to confirm this.

Androstenediol-induced restoration of responsiveness to influenza vaccination in mice.

Androstenediol (AED), a metabolite of dehydroepiandrosterone (DHEA) regulates innate and adaptive immune responses. To examine whether AED could effectively reverse the age-associated decline of antiviral immunity, 3-, 10-, and 22-month-old mice were treated with AED-sulfate (AED-S) for 45 days beginning 10 days prior to vaccination. Subsequently, mice were primed and boosted with suboptimal doses of a commercially-available trivalent influenza vaccine. Treatment of 10-month-old animals with AED-S during vaccination increased the titer of circulating antiviral immunoglobulin G to levels comparable with those in 3-month-old mice. Furthermore, AED-S treatment protected 10-month-old animals from intranasal challenge with a lethal dose of influenza virus 21 days after secondary vaccination. Although AED-S treatment of 22-month-old mice did not enhance vaccine responses and failed to protect against lethal challenge, the data from the 10-month-old animals suggest that treatment with AED-S will prevent the early manifestations of immunosenescence.

[The development of a new generation of pertussis vaccine]. / Razrabotka kokliushnoi vaktsiny novogo pokoleniia.

The results of the weight gain test on mice have shown that acellular pertussis vaccine is less toxic than the pertussis component of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine due to a lower content of endotoxin in the acellular vaccine; but the leukocytosis-promoting and histamine-sensitizing activities of JNIH-6 and adsorbed DPT vaccines are indicative of incomplete inactivation of Bordetella pertussis toxin. The content of incompletely inactivated B. pertussis toxin is practically the same in both preparations, constituting 1/100-1/200 of the calculated initial activity. For this reason, the use of the new pertussis vaccine also involves a risk of development of serious postvaccinal reactions and/or complications caused by this toxin. Search for the optimum method of inactivation of B. pertussis main toxin should be continued. As shown by the enzyme immunoassay, acellular pertussis vaccine used in the same immunizing dose as adsorbed DPT vaccine induces a more intensive immune response to hemagglutinin and B. pertussis toxin. This is due to higher residual toxicity of the corpuscular component of adsorbed DPT vaccine. Induction of antibodies to B. pertussis toxin has been shown to decrease in response to injection of acellular pertussis vaccine containing a certain residual amount of incompletely inactivated B. pertussis toxin.