Evidence map›Paper›PMID 40557164›Full record

ArticleFrontiers in immunology2025

Sub-neutralizing levels of antibodies against RSV F protein enhance RSV infection via Fc-FcγR interactions.

Tingting Luo, Xin Zhao, Yi Lu, Wen Tan, Bingming Peng, Li Zhong, Jinhua Ma, Chenghao Mei, Huaqin Bu, Daiyin Tian

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
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

10 authors.

Tingting Luo *Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Xin Zhao *Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Yi LuDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Wen TanDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Bingming PengDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Li ZhongDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Jinhua MaDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Chenghao MeiDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Huaqin BuDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Daiyin TianDepartment of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, and antibody-dependent enhancement (ADE) presents a significant challenge in vaccine and antibody development. This study investigated the molecular mechanism of ADE mediated by sub-neutralizing antibodies against RSV F protein. We demonstrated that anti-RSV F antibody could facilitate RSV attachment and endocytosis into cells via Fc-Fc gamma receptor (FcγR) interactions while only at sub-neutralizing levels, it increased RSV replication and release, thereby inducing ADE. ADE was abrogated following the secondary occlusion of F protein using nirsevimab Fab fragments. During ADE, intracellular inflammatory signaling pathways were overactivated, resulting in elevated secretion of pro-inflammatory factors (IL-1β, IL-6, TNF-α). FcγRI was identified as the dominant receptor of ADE through blockade experiments, and dual inhibition of FcγRI and TLR4 abolished ADE, highlighting their synergistic role. Furthermore, ADE-induced cytokines upregulated FcγRs expression, creating a self-reinforcing inflammatory loop. Overall, our findings indicated that (1) sub-neutralizing F-specific antibodies increase RSV entry via FcγRs, whereby partially unsealed F protein allows subsequent membrane fusion and enhances replication; (2) RSV ADE pathogenesis involves the coordination of FcγRI and TLR4 signaling pathways, and is amplified by cytokine-driven upregulation of FcγRs. These findings are helpful for the development of next-generation antibody and vaccine against RSV.

Indexed as

Antibodies, NeutralizingAntibodies, ViralAntibody-Dependent EnhancementReceptors, IgGRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsViral Fusion ProteinsAnimalsCytokinesHumansRespiratory Syncytial VirusesVirus InternalizationVirus ReplicationAntibodies, NeutralizingAntibodies, ViralCytokinesF protein, human respiratory syncytial virusReceptors, IgGViral Fusion Proteinsantibody-dependent enhancementFc gamma receptornirsevimabrespiratory syncytial virusviral lifecycle

Identifiers

PMID40557164
PMCPMC12185493

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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.