Evidence map›Paper›PMID 41622397›Full record

ArticleInfectious diseases and therapy2026

IgG4 Neutralization and Sustained Total IgG Fc-Effector Functions Following Repeated SARS-CoV-2 Vaccination with mRNA-1273.

Paulina Kaplonek, Harry Bertera, Diana W Lee, Deniz Cizmeci, Wen-Han Yu, Kai Wu, Spyros Chalkias, Rahnuma Wahid, Darin Edwards, Galit Alter and 1 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Infectious diseases and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04470427 (A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT04470427 phase3completednot on this map

A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older

TypeinterventionalSponsorModernaTX, Inc.Ran2020 to 2022Enrolled30,415ConditionsSARS-CoV-2ArmsmRNA-1273, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. 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.

Paulina KaplonekModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Harry BerteraModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Diana W LeeModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Deniz CizmeciModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Wen-Han YuModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Kai WuModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Spyros ChalkiasModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Rahnuma WahidModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Darin EdwardsModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Galit AlterModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA.
Carole HenryModerna, Inc, 325 Binney Street, Cambridge, MA, 02142, USA. carole.henry@modernatx.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDetailed characterization of the antibody profile induced by SARS-CoV-2 mRNA vaccines has shown that repeat dosing boosts all immunoglobulin G (IgG) subclasses, with a notable emergence of antigen-specific IgG4 antibodies. While the IgG4 subclass is traditionally associated with limited Fc-effector functions, its role in SARS-CoV-2 mRNA vaccine-induced immunity remains unclear.

methodsThis study tracked IgG subclass dynamics, IgG Fc-mediated functions, and neutralization following immunization with two or three doses of Moderna SARS-CoV-2 mRNA vaccine (mRNA-1273) in healthy adults.

resultsWe observed robust spike-specific IgG1 and IgG3 responses after the primary series (two doses) and booster dose, with a significant increase in IgG4 responses after repeated dosing. Despite this rise in spike-specific IgG4 antibodies, strong Fc-effector functions were maintained at the overall IgG level, including antibody-dependent cellular phagocytosis, antibody-dependent neutrophil phagocytosis, and antibody-dependent complement deposition, with no antagonism from IgG4 antibodies. Additionally, IgG4 antibodies exhibited enhanced affinity and potent neutralization, complementing IgG1-driven responses.

conclusionsThese findings suggest that elevated IgG4 responses did not antagonize overall Fc-mediated effector mechanisms, indicating that mRNA-1273 induces a multi-subclass antibody response that preserves antiviral functionality.

trial registrationNCT04470427.

Indexed as

Antibody profilingCOVID vaccineFc-effector functionsIgG4mRNA-1273SARS-CoV-2

Identifiers

PMID41622397
PMCPMC12924805

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Registered trials

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.