Evidence map›Paper›PMID 41912532›Full record

ArticleNPJ vaccines2026

Self-amplifying COVID-19 mRNA vaccination induces longitudinally enhanced antibody function in a Phase 3 trial.

Kate S Levine, Ross Blanc, Qixin Wang, Hadar Malca, Rose Sekulovich, Hongfan Jin, Sophie Liu, Carole Verhoeven, Brian Sullivan, Igor Smolenov and 1 more

Abstract read
In one paragraph

Article in NPJ vaccines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Kate S Levine *Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Ross Blanc *Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Qixin WangDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Hadar MalcaDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Rose SekulovichArcturus Therapeutics, San Diego, CA, USA.
Hongfan JinArcturus Therapeutics, San Diego, CA, USA.
Sophie LiuArcturus Therapeutics, San Diego, CA, USA.
Carole VerhoevenArcturus Therapeutics, San Diego, CA, USA.
Brian SullivanArcturus Therapeutics, San Diego, CA, USA.
Igor SmolenovArcturus Therapeutics, San Diego, CA, USA. igor.smolenov@arcturusrx.com.
Ryan P McNamaraDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. rmcnamara@hsph.harvard.edu.

Funding

Bill and Melinda Gates Foundation INV-080712
6 · The paper itself

Abstract

Sustained and functional antibody responses to respiratory pathogens through vaccination is critical for global public health. The development and deployment of mRNA vaccines during the coronavirus disease 2019 (COVID-19) pandemic was a landmark achievement in modern medicine and ushered in a new age of vaccine innovation. The mRNA-based vaccines elicited strong antibody responses, both neutralizing and extra-neutralizing, against the viral Spike protein. The antibody levels waned with time since vaccination, and that coupled with the antigenic drift of the virus prompted updates to the mRNA vaccine composition and evaluation of other mRNA modalities. Self-amplifying mRNA (sa-mRNA) vaccines such as ARCT-154 can prolong antigen production and durability of humoral immune response post-immunization, and can thus be administered at a lower dose. How this translates into the overall humoral architecture compared to that shaped by conventional mRNA vaccinations, however, is unclear. Here, we analyze serum-based antibody responses in a subset of participants from a recent Phase III trial comparing neutralizing immune responses elicited by ARCT-154 and mRNA BNT162B2 as a post-hoc research. All participants had received three doses of mRNA COVID-19 vaccines and were randomized to receive a booster dose of ARCT-154 or BNT162B2. Primary outcomes of this research were to quantify waning responses against ancestral/wild type SARS-CoV-2 Spike (WT Spike) and a panel of diverse SARS-CoV-2 variant Spikes. Through a systems serology approach, we identified that the sa-mRNA vaccine ARCT-154 elicited a unique antibody response compared to BNT162B2 defined by a sustained, activating profile to the vaccine-encoded Spike protein and a broad spectrum of drifted Spikes. Notably, potently activating FcγRIIIA-binding antibodies showed a sustained stimulation in the ARCT-154-treatment arm, and this translated to an enhanced natural killer (NK) cell activation. The NK-activation through ARCT-154 was present for both target WT Spike and the antigenically drifted BA.5 Spike, which was the predominant form of SARS-CoV-2 during the observation period. Our results support a model whereby prolonged antigen expression and presentation moves immune profiles towards activating phenotypes with broad antigenic coverage.

Identifiers

PMID41912532
PMCPMC13199437

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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.