Poly(D,L-lactic-co-glycolic acid) microsphere delivery of adenovirus for vaccination.
Bibliographic record
Abstract
PURPOSE: To study the effect of encapsulation of recombinant adenovirus type 5 encoding Beta-galactosidase (Ad5-Betagal) in poly (D,Llactic-co-glycolic acid) (PLGA) microspheres on viral delivery to professional antigen presenting cells (APCs) in vitro, viral dissemination in vivo, and induction of protective immune responses in vivo. METHODS: PLGA microspheres containing Ad5-alphagal were prepared by a double emulsion solvent evaporation method. Encapsulation efficiency, in vitro release profile, in vitro cellular uptake and in vivo biodistribution of Ad5-alphagal loaded PLGA microspheres were determined using 125I-labeled Ad5-alphagal (125I-Ad5-alphagal). To evaluate the potential of PLGA microsphere delivery of Ad-alphagal for induction of antigen specific immune responses in vivo, Balb/c mice were immunized with the subcutaneous injection of the formulations then splenocytes of the immunized mice were assayed for cytotoxic T lymphocyte (CTL) activity against a variety of target cells in a 51Cr-release assay. Anti-alphagal antibody responses were assessed in the sera of the immunized mice by enzyme linked immunosorbent assay (ELISA). The effect of encapsulated Ad5-alphagal immunization on protection against a tumor challenge was tested in a murine artificial metastatic lung tumor model with alphagalexpressing tumor cells, CT26.CL25. RESULTS: PLGA microspheres encapsulated Ad5-alphagal with 24.8 +/- 1.4 % encapsulation efficiency and 11.4 +/- 3.6 % of the encapsulated virus retained the functional activity. In vitro release study showed slow release (15% in 11 days) of the virus from the microspheres. PLGA microsphere delivery of Ad5-alphagal resulted in enhanced uptake of the virus by APCs with an increase in the transgene expression in vitro. Administration of the virus in the encapsulated form resulted in substantially decreased viral dissemination to remote organs and tissues as compared to the free virus. Encapsulated virus were capable of eliciting antigen specific CTL as well as antibody responses against alphagal and induced protective immune responses against lethal tumor challenge at a significantly lower infectious viral dose as compared to the free virus. CONCLUSION: PLGA microsphere with Ad5-alphagal enhances the delivery of virus to APCs with reduced viral dissemination in other organs and induces protective antigen specific immune responses against viral encoded transgene.
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How this classification was reachedexpand
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 | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".