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Record W4310710432 · doi:10.1038/s41541-022-00577-8

mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum

2022· article· en· W4310710432 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

Venuenpj Vaccines · 2022
Typearticle
Languageen
FieldMedicine
TopicMalaria Research and Control
Canadian institutionsAcuitas Therapeutics (Canada)
FundersU.S. Department of Health and Human ServicesNational Institutes of HealthBloomberg PhilanthropiesNational Institute of Allergy and Infectious DiseasesJohns Hopkins UniversityGeorge Washington University
KeywordsMalariaPlasmodium falciparumVirologyImmunogenicityVaccinationMalaria vaccineImmunityImmune systemTransmission (telecommunications)ImmunologyMedicineBiology

Abstract

fetched live from OpenAlex

Malaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.

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.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.381
Threshold uncertainty score0.642

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.011
GPT teacher head0.267
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it