Plant-made influenza virus-like particles (VLPs) activate dendritic cells and promote type 1 immune responses
Bibliographic record
Abstract
Cell-mediated immunity has shown to play a critical role in long-term anti-viral protection. Age-associated T-cell dysfunction in the elderly leaves this group especially vulnerable to viruses such as influenza. Specifically designing or optimizing vaccines for aged individuals would help to prevent diseases and decrease complications in this growing population. Central to the induction of long-term memory responses are dendritic cells (DCs). DCs have the ability to generate antigen-specific T-cell responses through antigen presentation on Major Histocompatibility Complex (MHC), upregulation of costimulatory molecules (CD86 and CD40) and cytokine secretion. In this study, bone-marrow-derived DC responses from young mice were first evaluated when stimulated with influenza hemagglutinin (from H1 and H5 strains) elicited by a novel plant-made Virus-Like-Particle (VLP) produced by Medicago Inc. We have found that H1-VLPs activate DCs from young mice by upregulating MHCII, CD86 and CD40. These VLPs also promote the production of pro-inflammatory cytokines such as IL-12p40, IL-12p70, IL-6, IL-1β and TNFα. H5-VLPs were found to have similar effects on DCs from young mice but are much less immunostimulatory than H1-VLPs. DC responses were significantly increased when VLPs were combined with the commonly used adjuvant, aluminum hydroxide (alum). H1- and H5-VLPs were also found to activate human monocyte-derived DCs by stimulating the upregulation of CD83 and CD86 and secreting inflammatory cytokines, similar to the observations in mice. DC:T-cell co-culture assays have shown that non-adjuvanted H1- and H5-VLPs improve the ability of DCs from young mice to stimulate CD4+ and CD8+ T-cell activation, differentiation and effector function. These findings further suggest that VLPs are able to stimulate the cross-presentation of antigens. H1-VLPs were also found to promote the activation of kinases typically activated downstream of innate immunity receptors (pattern recognition receptors) in DCs. H1-VLPs, but not H5-VLPs, were able to stimulate the transcription of IL-12p40 and pro-IL-1β. Only the combination of H1-VLP with alum allowed for the secretion of active IL-1β, suggesting that even though particulate, H1-VLPs cannot trigger the activation of the inflammasome. DCs from aged mice and humans were also activated by H1- and H5-VLPs but to a much lesser extent compared to DCs from young mice and humans. Further, DCs from aged mice produced more anti-inflammatory cytokines, such as IL-10, in response to H1-VLP combined with alum. Considering the suboptimal responses observed in DCs from aged mice and humans, it may be necessary to find targetable mechanisms or more appropriate adjuvants to improve the stimulatory effect of novel vaccine candidates in the aged immune system. Together, these results demonstrate that HA-VLPs have a direct stimulatory capacity on DCs and enhance their ability to promote subsequent Type 1 immune responses.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".