Anaphylactic Reactions Caused by the Covid-19 Vaccine Comirnaty in Anti-PEG Hyperimmune Pigs: Implications for the Safety of mRNA-LNP-based Vaccines and Other PEGylated Nanopharmaceuticals
Bibliographic record
Abstract
Background: mRNA-containing, PEGylated Covid-19 vaccines can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis in a small fraction of immunized people. A causal role of anti-PEG antibodies (Abs) has been proposed but not yet proven in a large animal model. Methods: Domestic pigs (n=6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v., and the rise of anti-PEG IgG and IgM were measured in serial blood samples with ELISA. During the plateau of seroconversion, in the 1-3 weeks postvaccination period, the animals were injected i.v. with 1/3 human dose of the PEGylated mRNA vaccine, Comirnaty, and the hemodynamic (PAP, SAP, pulse pressure), cardiopulmonary (HR, EtCO2,), hematological (WBC, granulocyte, lymphocyte and platelet counts) parameters and blood immune mediators (anti-PEG IgM and IgG antibodies, thromboxane B2, C3a) were measured as endpoints of anaphylaxis. Results: In about a week, the level of anti-PEG IgM and IgG rose 5-10-thousand-fold in all of 6 pigs immunized with Doxebo, after which time all animals developed anaphylactic shock to i.v. injection of 1/3 human dose of Comirnaty. The reaction, starting within 1 min, involved maximal pulmonary hypertension, decreased systemic pulse amplitude, tachycardia, granulopenia and thrombocytopenia. These physiological changes were paralleled by C3a and TXB2 rises in blood and were absent in non-immunized pigs. Conclusions: Consistent with previous studies, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty. Based on the involvement of C activation and identity of symptoms with those observed in pseudoallergy to PEGylated liposomes, the reaction represents C activation-related pseudoallergy (CARPA). The applied sensitization of the porcine CARPA model may help better understand these reactions, and, thus, make Comirnaty and other mRNA-LNP-based Vaccines and PEGylated Nanopharmaceuticals safer.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".