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Results for “FUNGAL VACCINES”

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At least 163 records · Page 9Linked to original sources

PubMed2001

V beta 6+ T cells are obligatory for vaccine-induced immunity to Histoplasma capsulatum.

We examined TCR usage to a protective fragment of heat shock protein 60 from the fungus, Histoplasma capsulatum. Nearly 90% of T cell clones from C57BL/6 mice vaccinated with this protein were Vbeta6+; the remainder were Vbeta14+. Amino acid motifs of the CDR3 region from Vbeta6+ cells were predominantly IxGGG, IGG, or SxxGG, whereas it was uniformly SFSGG for Vbeta14+ clones. Short term T cell lines from Vbeta6+-depleted mice failed to recognize Ag, and no T cell clones could be generated. To determine whether Vbeta6+ cells were functionally important, we eliminated them during vaccination. Depletion of Vbeta6+ cells abrogated protection in vivo and upon adoptive transfer of cells into TCR alphabeta(-/-) mice. Transfer of a Vbeta6+, but not a Vbeta14+, clone into TCR alphabeta(-/-) mice prolonged survival. Cytokine generation by Ag-stimulated splenocytes from immunized mice depleted of Vbeta6+ cells was similar to that of controls. The efficacy of the Vbeta6+ clone was associated with elevated production of IFN-gamma, TNF-alpha, and GM-CSF compared with that of the Vbeta14+ clone. More Vbeta6+ cells were present in lungs and spleens of TCR alphabeta(-/-) on day 3 postinfection compared with Vbeta14+ cells. Thus, a single Vbeta family was essential for vaccine-induced immunity. Moreover, the mechanism by which Vbeta6+ contributed to protective immunity differed between unfractionated splenocytes and T cell clones.

Adoptive Transfer↗

PubMed1991

Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity.

We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.

Animals↗

PubMed2001

CD4+ T cell-independent vaccination against Pneumocystis carinii in mice.

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. Moreover, deficient CD4+ T lymphocytes impair vaccination approaches to prevent opportunistic infection. Therefore, we investigated a CD4+ T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of anti-PC IgG in CD4-deficient mice. Vaccinated animals demonstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4-depleted splenocytes or serum conferred this protection to CD4-deficient mice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-deficient mice predominantly reacted to a 55-kDa PC antigen. These studies show promise for advances in CD4-independent vaccination against HIV-related pathogens.

Adoptive Transfer↗

PubMed2000

[Epidemiology, clinic and treatment of dermatomycoses caused by zoophilic dermatophytes] .

In the last 50 years the spectrum of agents of dermatophytoses changed. The change is remarkable especially in the case of zoophilic dermatophytes. Microsporum canis has displaced Trichophyton verrucosum. In the period from 1966 to 1970 2822 dermatophytoses were registered as occupational dermatoses in the former German Democratic Republic. In the following years the number of these diseases was continuously reduced, between 1981 and 1985 down to 995 cases. This reduction is predominantly the result of active immunoprophylaxis by means of inactivated, hydrolized vaccines, mainly by the Soviet live vaccine LTF-130. The scientific basis of this vaccination was established by Kielstein and co-workers. The treatment of Microsporum canis infection of the scalp requires the administration of systemically acting antimycotics over a long period (6-8 weeks).

Animals↗

PubMed2006

Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis.

We have shown that vaccination with the recombinant N terminus of Als1p (rAls1p-N) protects mice against disseminated and oropharyngeal candidiasis. We now report that vaccination of mice with a related candidate, rAls3p-N, induces a broader antibody response than rAls1p-N and a similar cell-mediated immune response. The rAls3p-N vaccine was equally as effective as rAls1p-N against disseminated candidiasis but was more effective than rAls1p-N against oropharyngeal or vaginal candidiasis. Antibody titers did not correlate with protection against disseminated candidiasis, but delayed-type hypersensitivity did. The rAls3p-N vaccine is a promising new vaccine candidate for further exploration to prevent systemic and mucosal candidal infections.

Animals↗

PubMed2002

Localization within a proline-rich antigen (Ag2/PRA) of protective antigenicity against infection with Coccidioides immitis in mice.

Subunits of a proline-rich coccidioidal antigen (Ag2/PRA) of Coccidioides immitis were analyzed by comparison as vaccines in mice. The optimal dose of plasmid vaccine encoding full-length Ag2/PRA was determined to be between 10 and 100 microg. Mice vaccinated with plasmids encoding amino acids (aa) 1 to 106 were as protective as full-length Ag2/PRA (aa 1 to 194). The subunit from aa 27 to 106 was significantly but less protective. Plasmids encoding aa 90 to 151 or aa 90 to 194 were not protective. Analogous results were obtained with recombinant vaccines of the same amino acid sequences. In addition, mixtures of aa 90 to 194 with either aa 1 to 106 or aa 27 to 106 did not enhance protection compared to the active single-recombinant subunits alone. Humoral response of total immunoglobulin G (IgG) and subclasses IgG1 and IgG2a were detectable in subunit vaccinations but at significantly (100-fold) lower concentrations than after vaccination with plasmids encoding full-length Ag2/PRA. Since virtually all protection by vaccination with full-length Ag2/PRA can be accounted for in the first half of the protein (aa 1 to 106), this subunit could make a multicomponent vaccine more feasible by reducing the quantity of protein per dose and the possibility of an untoward reactions to a foreign protein.

Amino Acid Sequence↗

PubMed1962

Immunization of mice against coccidioidomycosis.

Converse, J. L. (U. S. Army Chemical Corps, Frederick, Md.), M. W. Castleberry, A. R. Besemer, and E. M. Snyder. Immunization of mice against coccidioidomycosis. J. Bacteriol. 84:46-52. 1962-The observed lower virulence of Coccidioides immitis arthrospores of the M-11 strain compared with the Cash strain was ascribed to the lower ability of the M-11 spores to invade the lungs and brain. Endospores of strain M-11, grown in synthetic medium, were equally as virulent by the intraperitoneal route as arthrospores of strain Cash. Immunization of mice with viable strain M-11 arthrospores protected approximately 50% of the animals against challenge with strain Cash arthrospores. This was evidenced by lower mortality over a 5-month period and lack of gross pathological lesions in killed animals. Although fewer lesions resulted after the use of a viable vaccine, higher survival was obtained with formaldehyde-killed arthrospores. Either preparation tended to confine the infection to the peritoneal cavity.

Animals↗

PubMed1992

An inactivated vaccine against ringworm.

A new vaccine against ringworm, containing the inactivated Trichophyton verrucosum strain, was assessed on guinea pigs and calves under experimental conditions and on three herds of cattle under natural conditions. The vaccine elicited a distinct immune response of the cellular type. This type of immunity assessed by the migration inhibition test of leukocytes corresponded to the immunity evaluated by the challenge. In herds in which there were from 30 to 67% of naturally infected animals with T. verrucosum, two doses of the vaccine resulted in after 4 weeks a decrease of the number of animals with clinical changes from 40.5 to 100% depending on the group of animals under study.

Age Factors↗

PubMed2006

Multivalent recombinant protein vaccine against coccidioidomycosis.

Coccidioidomycosis is a human respiratory disease that is endemic to the southwestern United States and is caused by inhalation of the spores of a desert soilborne fungus. Efforts to develop a vaccine against this disease have focused on identification of T-cell-reactive antigens derived from the parasitic cell wall which can stimulate protective immunity against Coccidioides posadasii infection in mice. We previously described a productive immunoproteomic/bioinformatic approach to the discovery of vaccine candidates which makes use of the translated genome of C. posadasii and a computer-based method of scanning deduced sequences of seroreactive proteins for epitopes that are predicted to bind to human major histocompatibility (MHC) class II-restricted molecules. In this study we identified a set of putative cell wall proteins predicted to contain multiple, promiscuous MHC II binding epitopes. Three of these were expressed by Escherichia coli, combined in a vaccine, and tested for protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived beyond 90 days after intranasal challenge, and the majority cleared the pathogen. We suggest that the multicomponent vaccine stimulates a broader range of T-cell clones than the single recombinant protein vaccines and thereby may be capable of inducing protection in an immunologically heterogeneous human population.

Amino Acid Sequence↗

PubMed1983

Coccidioides immitis vaccine: potential of an alkali-soluble, water-soluble cell wall antigen.

C-ASWS-M, the alkali-soluble, water-soluble cell wall antigen of Coccidioides immitis mycelia, was evaluated for its vaccine potential in mice. Vaccination with 0.5-, 1.5-, or 3-mg doses of C-ASWS-M in complete Freund adjuvant provided a significant level of protection against intraperitoneal challenge with 1,500 arthroconidia (P < 0.0001 with each dose). Vaccination with 1 mg of C-ASWS-M protected mice against intranasal challenge with 50 (P < 0.05) and 500 (P < 0.01) arthroconidia, but not against intranasal challenge with 1,500 arthroconidia (P > 0.05).

Animals↗

PubMed2006

The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is broadly active against disseminated candidiasis.

We have previously shown that vaccination with a vaccine based on the recombinant N-terminal domain of Als1p (rAls1p-N) protected BALB/c mice against disseminated infection caused by a single strain of Candida albicans (A. S. Ibrahim, B. J. Spellberg, V. Avenissian, Y. Fu, S. G. Filler, and J. E. Edwards, Jr., Infect. Immun. 73:999-1005, 2005, and B. J. Spellberg, A. S. Ibrahim, V. Avenissian, S. G. Filler, C. Myers, Y. Fu, and J. E. Edwards, Jr., Infect. Immun. 73:6191-6193, 2005). Here we show that the rAls1p-N vaccine also improves survival of outbred mice from disseminated candidiasis and that it is active against multiple virulent strains of C. albicans and non-C. albicans spp.

Animals↗

PubMed1978

[Quantitative test for evaluating immunoreactivity in vaccinated mice with coccidioidosis].

The interaction between hypersensitivity of delayed type and the severity of infection was studied in albino mice vaccinated and survived after the intranasal infection with 100 LD50 of Coccidioidosis immitis (pulmonary model of coccidiasis). The method of determination of the weight of the lungs and edema of the paw pads after the administration of the specific antigen permitted to assess the intensity of immunity quantitatively. There was an inverse correlation between the weight of the affected lungs and edema of the limbs, and in case of pregressive development of coccidioidosis--between the weight of the body and the lungs. A formula for determining the immunoreactivity index in the vaccinated mice infected with the causative agents of lung infections, in the mechanism of whose defence the prevailing role was played by cellular immunity, is suggested.

Animals↗

PubMed1981

Treatment of equine phycomycosis by immunotherapy and surgery.

Treatment of equine phycomycosis with a vaccine derived from ultrasonicated hyphae of Hyphomyces destruens was attempted in 30 cases of clinical hyphomycosis, 10 cases of hyphomycosis following unsuccessful surgery and 5 cases of basidiobolomycosis. Approximately 53% of animals with clinical hyphomycosis were cured after vaccination, while a further 33% clinically improved. All horses with hyphomycosis treated within 2 weeks of unsuccessful surgery were cured. There was no response to vaccination with a Hyphomyces preparation in horses with basidiobolomyucosis, while surgery alone resulted in a cure of approximately 69%. Animals tolerated the vaccination procedures well. In all cases there was a moderate to severe reaction at the site of subcutaneous injection which subsided within 96 hours. In approximately 30% of injections a sterile abscess formed at the site but responded promptly to treatment. Response to vaccination at the site of the lesion was observed within 7 to 10 days of first injection. There was progressive reduction of pruritus, drying of the surface of the lesion, expulsion of kunkers, fibrosis of the granuloma, and eventually complete epithelialisation.

Animals↗

PubMed2002

Interplay between protective and inhibitory antibodies dictates the outcome of experimentally disseminated Candidiasis in recipients of a Candida albicans vaccine.

Mice immunized with heat-inactivated, whole yeast-form cells (Y cells) of Candida albicans developed intense, specific humoral and cell-mediated immune responses. However, they were modestly protected against a lethal challenge by the fungus, and their sera did not confer passive protection upon nonimmunized animals. Surprisingly, this immune serum conferred an elevated degree of passive protection to normal and SCID mice when preadsorbed on whole C. albicans cells. After adsorption, no antibodies specific to mannoprotein (MP)-rich extracts or secretions were detected by indirect enzyme-linked immunosorbent assay and no serum reaction with the fungal cell surface was seen in immunofluorescence assays. However, this serum had totally preserved the level of other antibodies, in particular those reacting with beta-1,3 and beta-1,6 glucan (GG). The hypothesis that anti-GG antibodies contributed to the passive protection was suggested by the following circumstantial evidence: (i) mice immunized with C. albicans cells treated with dithiothreitol and protease (YDP cells), which exposed GG on their surfaces and generated anti-GG but not anti-MP antibodies, were substantially protected against a lethal fungus challenge; (ii) the sera, and their immunoglobulin fractions, of mice immunized with YDP cells transferred protection to nonimmune animals; and (iii) this passive protection was substantially abolished by preadsorption on GG but not on intact cells. Overall, our findings demonstrate that some anti-Candida antibodies can block the protective potential of immune serum, a potential to which anti-GG antibodies appear to contribute. Our observations may also help explain why subjects with elevated anti-Candida antibody titers, inclusive of anti-MP and anti-GG antibodies, remain nonetheless susceptible to invasive candidiasis.

Animals↗

PubMed1982

[Evaluation of the immunogenic properties of live and killed vaccines against trichophytosis of guinea pigs and calves].

Ten variants of vaccines against trichophytosis were prepared. The vaccines were live and killed, nonadsorbed and adsorbed on aluminum hydroxide. The effectiveness of these vaccines was tested in laboratory conditions in 90 guinea pigs and 8 calves and in 110 farm calves. In the experiments with guinea pigs it was shown that it is possible to immunize them against the virulent strain T. verrucosum, where live vaccines proved to be the most effective, particularly those prepared from strain No 43 characterized by strong immunogenic properties. Vaccination of calves as that of guinea pigs appeared to be a procedure effectively protecting animals from experimental infection. In general, live vaccines used for immunization of calves caused full immunity of animals against a dose evoking infection after eight days since immunization. It is to be stressed that live vaccine prepared from the virulent strain No 43 evoked immune conditions after 4 weeks. Prophylactic vaccination of calves in nurseries in which trichophytosis has stationarily occurred for years gave positive results. Over eight months of observation a distinct decrease of the disease as well-as a weakened and shortened course of the disease were found.

Animals↗

PubMedDate not supplied

Strategies for the development of a vaccine against ringworm.

Resolution of lesions and subsequent protection against ringworm is primarily associated with the development of a cell-mediated immune (CMI) response, in which stimulation of Type-1 lymphocytes and cytokines such as interleukin-2 (IL-2), IL-12 and interferon gamma are significant. Type-2 lymphocyte activation and antibody formation seem a feature of chronic disease states, rather than protection, and are antagonistic to a Type-1 cell response. Initial studies on ringworm vaccines should be directed at identifying and characterizing dermatophyte antigens elaborated during spore germination and early hyphal growth, and the method of their presentation which best potentiates Type-1 cell-associated events, and primes the recipient for a subsequent CMI response.

Animals↗

PubMed2002

Partial protection against experimental vaginal candidiasis after mucosal vaccination with heat-killed Candida albicans and the mucosal adjuvant LT(R192G).

The effectiveness of a mucosal vaccine composed of heat-killed Candida albicans (HK-CA) or C. albicans culture filtrate (CaCF) in conjunction with the mucosal adjuvant LT(R192G) against vulvovaginal candidiasis was examined in an estrogen-dependent murine model. Mice vaccinated intranasally with HK-CA + LT(R192G) exhibited a significant but short-lived protection accompanied by a vigorous delayed-type hypersensitivity response as well as high titers of circulating C. albicans-specific antibodies. Surprisingly, the levels of antigen-specific antibodies in the vaginal secretions of protected mice were negligible and no correlates of vaginal-associated Type 1 or Type 2 cytokines were observed. Vaginal priming with C. albicans before vaccination did not alter the protective outcome. Immunization with CaCF + LT(R192G) induced a discrete level of protection when administered intrarectally but not intranasally. These results suggest that mucosal vaccination can afford partial protection against vulvovaginal candidiasis, but the precise immune mechanisms responsible for protection are complex and as yet, not well understood.

Adjuvants, Immunologic↗

PubMed2005

Is a vaccine needed against Candida albicans?

The development of a useful Candida vaccine is a distinct possibility despite the fact that individuals with a lifetime of commensal sensitization do not develop sterile immunity to the organism. An effective Candida vaccine would be invaluable in preventing hematogenously disseminated candidiasis, as well as mucocutaneous disease. This review is a discussion of our current understanding of the interplay between commensal and pathogenic forms of Candida albicans and approaches toward active and passive immunoprevention against candidiasis.

Candida albicans↗