Systemic and Mucosal Antibody Responses to SARS-CoV-2 Variant-Specific Prime-and-Boost and Prime-and-Spike Vaccination: A Comparison of Intramuscular and Intranasal Bivalent Vaccine Administration in a Murine Model
Bibliographic record
Abstract
Background: The rapid genetic evolution of SARS-CoV-2 has led to the emergence of immune-evading, highly transmissible variants of concern (VOCs). This prompts the need for next-generation vaccines that elicit robust mucosal immunity in the airways to directly curb viral infection. Objective: Here, we investigate the impact of heterologous variant prime–boost regimens on humoral responses, focusing on intramuscular (IM) and intranasal (IN) routes of administration. Using a murine model, we assessed the immunogenicity of unadjuvanted protein boosts with Wu-1, Omicron BA.4/5, or Wu-1 + BA.4/5 spike antigens following monovalent or bivalent IM priming with mRNA-LNP vaccines. Results: IM priming induced strong systemic total and neutralizing antibody responses that were further enhanced by IN boosts with BA.4/5. IN boosting achieved the broadest serum neutralization across all VOCs tested. Notably, bivalent mRNA-LNP IM priming induced robust, cross-variant serum neutralizing antibody production, independent of subsequent IN boost combinations. Conclusions: Our findings highlight the benefit of including distinct antigenic variants in the prime vaccination followed by a variant-tailored IN boost to elicit both systemic and mucosal variant-specific responses that are potentially capable of reducing SARS-CoV-2 transmission.
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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 | 0.000 |
| 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 | 0.000 |
| 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".