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At least 109 records · Page 6Linked to original sources

Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs: a possibility for the control of Candida-related atopic dermatitis.

In some cases of atopic dermatitis (AD), a possible pathological contribution to disease development by Candida albicans (C. albicans) has been suggested. AD patients with severe symptoms showing positive capsulated hydrolic carrier polymer radioallergosorbent test (CAP-RAST) against C. albicans demonstrated significantly higher levels of serum IgE Abs than did AD patients with mild symptoms. Based on the clinical facts, we have postulated that elimination of C. albicans by mucosal vaccination may lead to the restoration of severe symptoms in AD patients. For this purpose, we have developed an allergic murine model. Mice which were systemically challenged with C. albicans-associated antigen, manganese superoxide dismutase (MnSOD) or secreted aspartic proteases 2 (SAP2), together with alum, exhibited hyper IgE Abs. Systemically primed mice were then immunized with MnSOD or SAP2 plus cholera toxin (CT) as mucosal adjuvant through the nasal route. Interestingly, nasally immunized mice showed increased levels of Candida Ag-specific IgA Ab in fecal and nasal washes as well as in saliva samples but unchanged levels in Ag-specific IgE responses. Consistent with the Ab levels, high numbers of Candida Ag-specific IgA Ab-forming cells were induced in mononuclear cells isolated from intestinal lamina propria, nasal passages and salivary glands of nasally vaccinated mice with Ag plus CT. Furthermore, nasal immunization using MnSOD or SAP2 together with CT resulted in the elimination of colonized C. albicans from the intestinal tract. These results also suggest a potential role of mucosal vaccination in the control of C. albicans in patients with allergic diseases, including AD, although more research is needed to establish this therapeutic approach for mucosal vaccination.

Adjuvants, Immunologic↗

Liposomes containing Candida albicans ribosomes as a prophylactic vaccine against disseminated candidiasis in mice.

This study describes the development of prophylactic anti-Candida vaccine which combines the advantages of Candida albicans ribosomes as antigen(s) and of liposomes as carrier/adjuvant with minimal side-effects, which could be suitable for human use. The liposomal vaccine was composed of C. albicans ribosomes and the lipids dimyristoyl phosphatidyl choline (DMPC) and dimyristoyl phosphatidyl glycerol (DMPG) (9:1 molar ratio). Some of the vaccines contained Lipid-A (LA) as an additional adjuvant. The vaccine was prepared by two methods: (I) dehydration by lyophylization of small liposomes in the presence of the Candida ribosomes (DRV method); (II) colyophylization of DMPC/DMPG (9:1 mole ratio) in tertiary butanol with aqueous dispersion of Candida ribosomes. In both cases a dry powder was obtained which was rehydrated to form large multilamellar vesicles. The efficacy of the vaccines in mice was tested by their protectivity against a challenge with C. albicans, as assessed by survival rate, induction of cell mediated immunity (measured by delayed type hypersensitivity-DTH) and anti-Candida antibody titer. Unimmunized mice and mice vaccinated by ribosomes supplemented with incomplete Freund's adjuvant (IFA) were used as controls. The results indicated that the liposomal vaccines were effective at least as the IFA-based vaccine. The study indicates the feasibility of developing an efficacious anti-Candida vaccine for human use.

Animals↗

New immunotherapeutic strategies to control vaginal candidiasis.

The widespread occurrence of mucosal infections caused by Candida, in particular recurrent vulvovaginal candidiasis among fertile-age women, together with the paucity of safe candidacidal antimycotics, have prompted a great number of investigations into the immunotherapy of candidal vaginitis. This article will discuss three different experimental approaches demonstrated to be potentially transferable to human disease: (1) the use of antibodies against well-defined cell-surface adhesins or enzymes; (2) the generation of yeast killer-toxin-like candidacidal anti-idiotypic antibodies and their engineered molecular derivatives (e.g. single chains, peptides); and (3) the generation of therapeutic vaccines and immunomodulators.

Antibodies, Fungal↗

Neutrophil role in pulmonary paracoccidioidomycosis depends on the resistance pattern of hosts.

The immunoprotective and immunomodulatory role of neutrophils during pulmonary infection of resistant (A/J) and susceptible (B10.A) mice to Paracoccidioides brasiliensis was investigated. First, comparative studies about early cellular influx to the lungs demonstrated higher numbers of neutrophils in susceptible rather than in resistant mice. Neutrophil depletion resulted in decreased survival times of susceptible but not resistant mice. In both mouse strains, depletion led to increased fungal burdens at Week 1 of infection; however, only susceptible mice remained with increased pulmonary fungal loads and presented a dramatic fungal dissemination to liver and spleen. At Week 1 of infection, treated and untreated B10.A and A/J mice were negative for delayed-type hypersensitivity (DTH) reactions, which remained negative for the susceptible strain. In contrast, from the second week onward, control and neutrophil-depleted, resistant mice became positive for DTH reactions. In B10.A mice, neutrophil depletion resulted in increased levels of interleukin (IL)-12 and IL-4 in the lungs, high levels of hepatic cytokines, and increased synthesis of T helper cell type 1 (Th1)- and Th2-regulated antibodies [immunoglobulin G1 (IgG1), IgA, and IgG3]. In neutrophil-depleted A/J mice, high levels of pulmonary IL-12 and granulocyte macrophage-colony stimulating factor were concomitant to diminished levels of hepatic cytokines and increased amounts of Th1-regulated isotypes (IgG2a, IgG2b, and IgG3). Differently from primary infection, neutrophil depletion did not alter immunoprotection in secondary paracoccidioidomycosis. As a whole, our data showed that the genetic patterns of hosts exert an important influence on the immunoprotective and immunoregulatory functions of neutrophils, which appear to be essential in situations devoid of cell-mediated immunity.

Animals↗

[Testing the protective effectiveness of avirulent vaccines against trichophytosis in cattle].

The protective action of live avirulent vaccine against bovine trichophytosis, produced by the Bioveta National Corporation at Ivanovice na Hané, was very good and fully comparable with the earlier vaccine produced from the virulent live culture of Trichophyton verrucosum. Experimental challenge with a massive dose of a virulent strain of T. verrucosum produced only minor surface dermal changes in the calves vaccinated with these vaccines, but these changes spontaneously disappeared in a short time. In the control non-vaccinated calves, large and deep lesions were induced by the challenge, spreading to the neighbouring tissues. Compared with both live biopreparations, the protective effect of inactivated vaccine prepared by the irradiation of virulent vaccine with Co60 was much lower.

Animals↗

[Vaccination of cattle against trichophytosis in the prevention and control of dermatophytic zoonoses].

The results of a four-year study of the occurrence of trichophytosis in some cattle stocks in the Pardubice district are presented. The monoetiological nature of this mycosis is documented; this mycosis can be successfully controlled by vaccination. Experiments demonstrated a good activity of antigens which were included in commercial vaccines. The evaluation of the antibody reaction in test rabbits and in vaccinated and spontaneously infected cattle was subjected to critical analysis. However, the main point of the whole study is a general evaluation of the possibilities and limitations of cattle vaccination against trichophytosis as ensues from literary data and from the authors' experience. The results indicate that in permanent application of all the hitherto used preventive and repressive methods a technically correct active immunization of cattle means the best contribution to the control of trichophytosis. The discussion deals with the theoretical problems of the nature and duration of immunity to these diseases and with the choice of the best vaccines and vaccination procedures.

Animals↗

Resistance to challenge and macrophage activity in mice previously vaccinated with formalin-killed Cryptococcus neoformans.

Mice were vaccinated with formalin-killed Cryptococcus neoformans either intranasally, intravenously, or intraperitoneally. Resistance to lethal challenge and in vitro phagocytic activity of alveolar and peritoneal macrophages was studied. Increased resistance to lethal challenge was seen following vaccination by each of the three routes but increased phagocytic activity was seen only in alveolar macrophages from mice vaccinated intranasally.

Administration, Intranasal↗

Immunity in cattle vaccinated against ringworm.

Protective properties of a live, freeze-dried vaccine against ringworm, produced by Bioveta, Ivanovice na Hané, Czechoslovakia, were tested in a group of 422 calves. Vaccinated and control calves were challenged by epicutaneous inoculation of a virulent culture of Trichophyton verrucosum. Between 4.4 and 9.5% of calves challenged between days 14 and 25 after revaccination showed only mild clinical signs of ringworm and 99-100% were fully protected from day 28, the immunity persisting for at least one year. All control calves showed signs of ringworm after challenge. In most cases, extensive mycotic lesions, also penetrating into deep skin layers, were observed. Protective properties of the Czechoslovak vaccine and a USSR vaccine were high and comparable.

Animals↗

Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice.

Coccidioides immitis antigens which stimulate a T helper cell 1 (Th1) pathway of host immune response are considered to be essential components of a vaccine against coccidioidomycosis. Recombinant urease (rURE) and recombinant heat shock protein 60 (rHSP60) of C. immitis were expressed in Escherichia coli and tested as vaccine candidates in BALB/c mice. A synthetic oligodeoxynucleotide which contained unmethylated CpG dinucleotides and was previously shown to enhance a murine Th1 response was used as an immunoadjuvant. T cells isolated from the spleens and lymph nodes of the rURE- and rHSP60-immune mice showed in vitro proliferative responses to the respective recombinant protein, but only those T lymphocytes from rURE-immunized mice revealed markedly elevated levels of expression of selected Th1-type cytokine genes. BALB/c mice immunized subcutaneously with rURE and subsequently challenged by the intraperitoneal (i.p.) route with a lethal inoculum of C. immitis arthroconidia demonstrated a significant reduction in the level of C. immitis infection compared to control animals. rHSP60 was much less effective as a protective antigen. Evaluation of cytokine gene expression in lung tissue and levels of recombinant urease-specific immunoglobulins (immunoglobulin G1 [IgG1] versus IgG2a) in murine sera at 12 days after challenge provided additional evidence that immunization with rURE stimulated a Th1 response to the pathogen. Urease was further evaluated by expression of the URE gene in a mammalian plasmid vector (pSecTag2A.URE) which was used to immunize mice by the intradermal route. In this case, 82% of the vector construct-immunized animals survived more than 40 days after i.p. infection, compared to only 10% of the mice immunized with the vector alone. In addition, 87% of the pSecTag2A.URE-immunized survivors had sterile lungs and spleens. These data support the need for further evaluation of the C. immitis urease as a candidate vaccine against coccidioidomycosis.

Animals↗

Antibodies to keyhole limpet hemocyanin cross-react with an epitope on the polysaccharide capsule of Cryptococcus neoformans and other carbohydrates: implications for vaccine development.

Cryptococcus neoformans causes a life-threatening meningoencephalitis in AIDS patients. Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid produce Abs that can be either protective or nonprotective. Because nonprotective Abs block the efficacy of protective Abs, an effective vaccine must focus the Ab response on a protective epitope. Mice immunized with peptide mimetics of GXM conjugated to keyhole limpet hemocyanin (KLH) with glutaraldehyde developed Abs to GXM. However, control peptides P315 and P24 conjugated to KLH also elicited Abs to GXM. GXM-binding Abs from mice immunized with P315-KLH were inhibited by KLH treated with glutaraldehyde (KLH-g), but not by P315. Furthermore, KLH-g inhibited binding of GXM by serum of mice immunized with GXM-TT, indicating that glutaraldehyde treatment of KLH reveals an epitope(s) that cross-reacts with GXM. Vaccination with KLH-g or unmodified KLH elicited Abs to GXM, but did not confer protection against C. neoformans, suggesting the cross-reactive epitope on KLH was not protective. This was supported by the finding that 4H3, a nonprotective mAb, cross-reacted strongly with KLH-g. Sera from mice immunized with either native KLH or KLH-g cross-reacted with several other carbohydrate Ags, many of which have been conjugated to KLH for vaccine development. This study illustrates how mAbs can be used to determine the efficacy of potential vaccines, in addition to describing the complexity of using KLH and glutaraldehyde in the development of vaccines to carbohydrate Ags.

Amino Acid Sequence↗

[The effectiveness of LTF 130 Trichophyton vaccine under field conditions].

The preventive action of ringworm vaccine LTF 130 was studied in calves. A number of these calves were found to develop ringworm despite vaccination when they came into contact with infected animals during the build-up of immunity. The incidence of ringworm was reduced when the animals were vaccinated at an early age or when the dosage was increased on vaccination later in life.

Animals↗