Impact of Systemic or Mucosal Immunity to Adenovirus on Ad-Based Ebola Virus Vaccine Efficacy in Guinea Pigs
Bibliographic record
Abstract
BACKGROUND: Approximately 35% of the North American population and an estimated 90% of the sub-Saharan African population have antibodies against adenovirus serotype 5 (AdHu5) that are capable of neutralizing AdHu5-based vaccines. In mice, intranasal delivery of AdHu5 expressing the Zaire ebolavirus glycoprotein human adenovirus serotype 5 (Ad) containing the genes for the Zaire ebolavirus glycoprotein (ZGP) under the expressional control of a cytomegalovirus immediate early promoter (CMV)) can bypass systemic preexisting immunity, resulting in protection against mouse-adapted Zaire ebolavirus (Mayinga 1976). METHODS: Guinea pigs administered an adenovirus-based Ebola virus vaccine either intramuscularly or intranasally in the presence of systemically or mucosally induced adenovirus immunity were challenged with a lethal dose of guinea pig-adapted Zaire ebolavirus (Mayinga 1976) (GA-ZEBOV). The humoral immune response was assayed to determine the effect of vaccine delivery route and preexisting immunity. RESULTS: Intramuscular or intranasal vaccination fully protected guinea pigs against a lethal GA-ZEBOV challenge. However, intramuscular vaccination in animals with systemically induced preexisting immunity resulted in low survival following challenge. Interestingly, intranasal vaccination protected guinea pigs with systemic preexisting immunity to AdHu5. Mucosal adenoviral immunity induced by intranasal administration of AdHu5 decreased protection following intranasal vaccination with the first-generation but not with the second-generation vaccine. CONCLUSIONS: Intranasal vaccination is an effective vaccine delivery route in the presence of systemic and, to a lower extent, mucosal preexisting immunity to the vaccine vector in guinea pigs.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".