Evidence map›Paper›PMID 30785039›Full record

ArticleMolecular therapy. Nucleic acids2019

Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines.

Kimberly J Hassett, Kerry E Benenato, Eric Jacquinet, Aisha Lee, Angela Woods, Olga Yuzhakov, Sunny Himansu, Jessica Deterling, Benjamin M Geilich, Tatiana Ketova and 9 more

Abstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 481 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
481citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

481 citing papers in PubMed, 1 synthesis or guideline pooled it.

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421 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Kimberly J HassettModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Kerry E BenenatoModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Eric JacquinetModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Aisha LeeModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Angela WoodsModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Olga YuzhakovModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Sunny HimansuModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Jessica DeterlingModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Benjamin M GeilichModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Tatiana KetovaModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Cosmin MihaiModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Andy LynnModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Iain McFadyenModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Melissa J MooreModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Joseph J SennModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Matthew G StantonModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Örn AlmarssonModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Giuseppe CiaramellaModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
Luis A BritoModerna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: luis.brito@modernatx.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency.

Indexed as

formulationimmunogenicityintramuscularlipidsLNPmRNAtolerabilityvaccines

Identifiers

PMID30785039
PMCPMC6383180

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.