mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice
Bibliographic record
Abstract
Plasmodium vivax poses significant challenges to malaria control due to its relapsing nature. This study explores the immunogenicity and efficacy of nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccines targeting the P . vivax circumsporozoite protein (PvCSP). Two mRNA constructs encoding PvCSP were designed and tested in mice. Despite lower protein expression, the vaccine encoding the wild-type signal peptide (SP) and glycosylphosphatidylinositol (GPI) anchor of PvCSP induced significantly higher antibody titers against the PvCSP and its repeat region compared with the mRNA construct with SP but without GPI. The immunogenicity of PvCSP mRNA-LNP vaccines was evaluated using various administration routes and immunization schedules. Both intradermal and intramuscular delivery generated dose-dependent antibody responses, but the former demonstrated superior responses at a lower dose. Conversely, intravenous administration resulted in very poor responses. Notably, administering a delayed third dose intramuscularly 5 months after the second dose resulted in significantly higher levels of anti-repeat region antibodies and enhanced T cell responses in both the spleen and liver. This delayed regimen provided strong protection against sporozoite challenge, with the magnitude and avidity of anti-repeat region antibodies linked to this protection. These findings highlight the potential of the nucleoside-modified mRNA-LNP vaccine platform in combating P . vivax pre-erythrocytic stage infection.
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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 | 0.000 | 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 | 0.000 | 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".