Primary characterization of a panel of monoclonal antibodies raised against the fungal pathogen Candida albicans
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Background: Candida albicans is an opportunistic pathogen responsible for non-life-threatening mucosal infections and is also a major cause of morbidity and mortality in immunosuppressed patients. While Candida infections can be treated with a variety of fungistatic antifungals, mortality rates from systemic candidiasis remain high. This fungi is capable of switching between various morphological forms including hyphae, associated with biofilm formation and tissue invasion, yeast, which is important for dissemination, the mating-competent opaque form and a commensal morphology that was recently observed in the gastro-intestinal tract. Methods: We immunized SJL and A/J mice with UV-killed hyphae, yeast or opaque C. albicans cells and used a ClonePixFL to select hybridoma clones that secrete immunoglobulins. These were then screened for anti-Candida monoclonal antibodies (mAbs) using an In-Cell ELISA assay. To date, we have produced 38 hybridoma cell lines and concentrated our characterization efforts on 23 mAbs that bind to live C. albicans cells. Results: Five mAbs recognize all morphological forms of C. albicans, 16 are hyphal-specific while 2 will only bind to opaque cells. In addition to C. albicans, 3 of the mAbs also recognize other fungal pathogens such as C. glabrata, C. tropicalis and C. dublininensis. All of the mAbs label the cell surface by immunofluorescence microscopy and 10 produce multiple bands or high-molecular weight smears in western blots. In order to narrow down the identity of mAb targets and to determine whether they recognize glycoproteins or glycans, we used the In-Cell ELISA assay to probe mannosylation (∆och1, ∆pmr1, ∆mnt1∆mnt2) and chitin synthase (∆chs2, ∆chs3, ∆chs8, ∆chs2∆chs8) mutants. We have also produced and probed reverse-phase protein microarrays spotted with total protein extracts from 2,357 GRACE C. albicans strains in the hyphal or yeast morphologies. In these strains, one gene copy is inactivated by insertional mutagenesis while the other allele is under the control of a repressible Tet-promoter. Conclusions: These assays allowed us to cluster the members of this mAb panel according to their target specificities and to prioritize them for future investigations aimed at evaluating their potential for therapeutic or diagnostic purposes.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it