Antibodies in Infectious Diseases: HIV Biomarker Discoveries, Complement Enhanced SARS-CoV-2 Neutralization and Vaccine Generation
Bibliographic record
Abstract
The main barrier towards an HIV cure is the presence of latently HIV-infected cells that make up the viral reservoir which persists through antiretroviral therapy. Although there is some leaky protein transcription in these latent cells, they evade immune surveillance and through homeostatic proliferation, maintain the viral reservoir. To eradicate the viral reservoir, one must be able to target it through the use of a biomarker. In the first part of this thesis, sea lamprey were immunized with latently HIV-infected T cells to generate a library of lamprey antibodies. 1273 antibodies were isolated and screened against HIV infected and non-infected primary cells. 25 antibodies were found to be specific to HIV infected cells which are currently being classified further.Due to the COVID pandemic, HIV research was placed on ‘hold’ in order to develop SARS-CoV-2 neutralization assays and COVID vaccine development efforts. In chapter 3 we report the SARS-CoV-2 neutralization titers of human convalescent sera were consistent across all disease states except for severe COVID-19, which yielded significantly higher neutralization titers. Heat inactivation of human convalescent serum was shown to inactivate complement proteins, and the contribution of the complement system in SARS-CoV-2 neutralization was often over 50% and mainly driven through the classical pathway. In some cases, heat inactivation completely abolished neutralization levels to undetectable levels. This effect was also observed in COVID-19 vaccinees and could be abolished in individuals who were being treated with anti-complement antibodies for other diseases. Safe and effective vaccines are needed to end the COVID-19 pandemic. In the final chapter we report the preclinical development of a lipid nanoparticle formulated SARS-CoV-2 mRNA vaccine. Tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Mouse immune sera elicited by PTX-COVID19-B vaccination neutralized SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada and had passed a phase 2 clinical trial.
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 | 0.000 | 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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".