The Anti-
            <i>Candida albicans</i>
            Vaccine Composed of the Recombinant N Terminus of Als1p Reduces Fungal Burden and Improves Survival in Both Immunocompetent and Immunocompromised Mice

Spellberg, Brad; Ibrahim, Ashraf S.; Avenissian, Valentina; Filler, Scott G.; Myers, Carter L.; Fu, Yue; Edwards, John E.

doi:10.1128/iai.73.9.6191-6193.2005

Cited by 73 publications

(48 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The avoidance of iron supplementation and blood transfusion, if possible, is also advisable [Spellberg and Ibrahim, 2010]. [Spellberg et al 2005b], antibodies against fungal antigens (e.g. efungumab, a recombinant monoclonal antibody fragment to the heat shock protein of C. albicans) [Pachl et al 2006], phagocytic cell-line-based immunotherapy (e.g.…”

Section: Preemptive Treatmentmentioning

confidence: 99%

Invasive fungal infections in acute leukemia

Bhatt

Viola

Ferrajoli

2011

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as b-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of antifungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drugdrug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

show abstract

Section: Preemptive Treatmentmentioning

confidence: 99%

Invasive fungal infections in acute leukemia

Bhatt

Viola

Ferrajoli

2011

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

show abstract

“…One standard formulation is Alhydrogel, a gelatinous matrix of aluminum hydroxide, which minimizes lot-to-lot variability and enables facile adsorption of proteins (5, 12). As noted by Hem et al, aluminum hydroxide in its dehydrogenated, crystalline form is chemically aluminum oxyhydroxide [AlO(OH)] (7), but in its aqueous phase, it acquires an additional water molecule to become aluminum trihydroxide [Al(OH) 3 ].We have developed a vaccine using the recombinant N terminus of the candidal adhesin Als3p (rAls3p-N), which has been shown to protect mice against otherwise-lethal disseminated candidiasis (8,9,15,16). The vaccine is also effective in combination with Alhydrogel diluted in phosphate-buffered saline (PBS) (8).…”

mentioning

confidence: 99%

“…We have developed a vaccine using the recombinant N terminus of the candidal adhesin Als3p (rAls3p-N), which has been shown to protect mice against otherwise-lethal disseminated candidiasis (8,9,15,16). The vaccine is also effective in combination with Alhydrogel diluted in phosphate-buffered saline (PBS) (8).…”

mentioning

confidence: 99%

“…Serum antibody titers from 1, 2, and 3 weeks postvaccination were determined by enzyme-linked immunosorbent assay of 96-well plates coated with 5 g/ml rAls3p-N, as we have described previously (9,16). While the antibody titers increased each week in vaccinated mice, the titers did not differ at any time point between the mice vaccinated with S-3 and those vaccinated with P-3 (P was 0.8, 0.5, and 0.6 at 1, 2, and 3 weeks, respectively) ( Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Considerable Differences in Vaccine Immunogenicities and Efficacies Related to the Diluent Used for Aluminum Hydroxide Adjuvant

Lin

Ibrahim

Avanesian

et al. 2008

Clin Vaccine Immunol

Self Cite

View full text Add to dashboard Cite

We are developing an anticandidal vaccine using the recombinant N terminus of Als3p (rAls3p-N). We report that although more rAls3p-N was bound by aluminum hydroxide diluted in saline than by aluminum hydroxide diluted in phosphate-buffered saline (PBS), its immunogenicity and efficacy were superior in PBS. Thus, protein binding, by itself, may not predict the efficacy of some vaccines with aluminum adjuvants.Hundreds of millions of doses of aluminum adjuvants have been administered to humans over the past century (5,11,12). One standard formulation is Alhydrogel, a gelatinous matrix of aluminum hydroxide, which minimizes lot-to-lot variability and enables facile adsorption of proteins (5, 12). As noted by Hem et al., aluminum hydroxide in its dehydrogenated, crystalline form is chemically aluminum oxyhydroxide [AlO(OH)] (7), but in its aqueous phase, it acquires an additional water molecule to become aluminum trihydroxide [Al(OH) 3 ].We have developed a vaccine using the recombinant N terminus of the candidal adhesin Als3p (rAls3p-N), which has been shown to protect mice against otherwise-lethal disseminated candidiasis (8,9,15,16). The vaccine is also effective in combination with Alhydrogel diluted in phosphate-buffered saline (PBS) (8). Vaccine efficacy requires an adjuvant, as the vaccine does not significantly improve survival if no adjuvant is utilized. To determine the optimal diluent for the continued development of the rAls3p-N vaccine, we assessed its relative binding to Al(OH) 3 , its immunogenicity, and its efficacy in the presence of PBS versus in the presence of saline. rAls3p-N (amino acids 17 to 432 of Als3p) was produced in Saccharomyces cerevisiae and purified by Ni-nitrilotriacetic acid matrix affinity purification as previously described (15). The isoelectric point of several batches of rAls3p-N was determined to be 7.1 using a Ready Gel IEF pH 5-to-8 gel (Bio-Rad) per the manufacturer's instructions (data not shown).To quantify protein binding to Al(OH) 3 , rAls3p-N was diluted to 0.2 mg/ml in saline (pH 6.5, 0.9% sodium chloride) or PBS (pH 7.40, 0.9% sodium chloride, 0.1% sodium-potassium phosphate), with or without 0.13 mg/ml of Alhydrogel (Brenntag Biosector, Frederikssund, Denmark). The solutions were vortexed, incubated for 30 min at room temperature, and centrifuged at 13,000 rpm for 10 min on a tabletop microcentrifuge. The protein concentration in the supernatant (i.e., unbound) was calculated by UV absorption as follows: (concentration without Alhydrogel -concentration with Alhydrogel)/(concentration without Alhydrogel). Protein binding was found to be slightly but significantly higher in the presence of saline than in the presence of PBS (median

show abstract

“…However, antifungal chemotherapy is not often effective for invasive mycoses when the host immune system is significantly suppressed. Although immune therapy particularly vaccination is recently getting popular for the treatment of invasive mycoses, vaccination is not always effective to certain patients with feeble immunogenic responses [5,10,25,26]. Therefore, treatment measures which can stimulate immunity in these patients or which is effective even for immunosuppressed patient, for example, antifungal substances associated with host defenses, have been paid much attention [14,17].…”

mentioning

confidence: 99%

Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

Okazaki

Asakura

Sugimoto

et al. 2009

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. It has been reported that administration of Candida albicans into mouse induces an antifungal activity in serum, which has been identified as transferrin. In the present study, we show that not only C. albicans, but also other fungus such as Cryptococcus neoformans or Aspergillus fumigatus similarly can induce an antifungal activity in mouse serum. This antifungal activity was inhibited by the addition of ferrous ion, indicating that the growth inhibition of C. albicans was due to deficiency of ferrous ion, which may be caused by transferrin. Indeed, addition of transferrin in an in vitro assay system using RPMI1640 culture medium inhibited the growth of C. albicans, C. neoformans or A. fumigatus. However, when C. albicans was grown in RPMI1640 medium with 10% fetal bovine serum (FBS), transferrin was unable to inhibit the growth of C. albicans, in sharp contrast, when C. albicans treated mouse serum was added instead of FBS, the growth of the organism was inhibited. Similar results were obtained when C. neoformans or A. fumigatus was used. Taken together, the results suggest that antifungal activity induced by C. albicans, C. neoformans or A. fumigatus was not due to transferrin but likely due to other unknown serum proteins, which may cut off the source of iron for the growth of these fungi.

show abstract

The Anti- Candida albicans Vaccine Composed of the Recombinant N Terminus of Als1p Reduces Fungal Burden and Improves Survival in Both Immunocompetent and Immunocompromised Mice

Cited by 73 publications

References 20 publications

Invasive fungal infections in acute leukemia

Invasive fungal infections in acute leukemia

Considerable Differences in Vaccine Immunogenicities and Efficacies Related to the Diluent Used for Aluminum Hydroxide Adjuvant

Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

Contact Info

Product

Resources

About