The development and evaluation of medical countermeasures against severe acute respiratory syndrome coronavirus type 2
Bibliographic record
Abstract
The SARS-CoV-2 pandemic has demonstrated the need for faster and more efficient ways to produce diagnostics, therapeutics and vaccines against unknown infectious diseases. This study evaluated the ability of a baculovirus expression vector system (BEVS) to produce immunogenic antigens for use in diagnostic tests and to produce monoclonal antibody (mAb) therapies. This study also evaluated a novel approach to vaccine development: targeting antigen to MHC-II via an immunotargeted vaccine (ITV) as well as a viral vectored vaccine. Using the genetic sequences of SARS-CoV-2, the full-length soluble Spike protein (SS), the S1 domain, receptor binding domain (RBD) and nucleocapsid protein (NP) of SARS-CoV-2 were expressed using the BEVS. These proteins were used to immunize mice to produce mAbs which were proven useful in competitive ELISA development, immunostaining and neutralization of SARS-CoV-2 Wuhan and Delta variants. These mAbs were then further characterized by epitope mapping as well as gene and amino acid sequencing of the variable heavy and light chains. Two unadjuvanted ITVs using the RBD from SARS-CoV-2 were evaluated for their ability to protect ferrets challenged with SARS-CoV-2. The ITVs elicited neutralizing antibody responses after one immunization whereas an adjuvanted subunit vaccine required a boost. Following challenge, ITV immunized ferrets had lower viral titres in nasal washes and were also bright and responsive throughout the duration of challenge. Ferrets immunized with the adjuvanted vaccine and unvaccinated ferrets experienced symptoms consistent with mild to severe clinical disease. A Newcastle disease viral vectored vaccine expressing a pre-fusion stabilized spike protein of SARS-CoV-2 was intranasally immunized into ferrets at low and high doses and the sera was tested for neutralization potential. At both high and low doses, the serum was able to neutralize SARS-CoV-2 Wuhan, Delta B.1.617.2 and Omicron BQ.1 variants. The results from these studies form a basis for further study of these platforms and their potential for implementation in the event of another pandemic as well as for currently circulating viruses in both human and animal populations. This study has the potential to directly contribute to both Canadian and global biosecurity and preparedness.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| 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".