Evidence map›Paper›PMID 41462459›Full record

ArticleBMC medicine2025

Ad5-boosted COVID-19 vaccine reduces symptomatic BA.5 infection via cross-neutralizing antibodies and NK cell immunity.

Tingting Cui, Siyi Liu, Tingting Wang, Yarui Liu, Xinyue Liang, Faming Chen, Mingzhu Huang, Xiaoling Su, Tao Song, Jie Su and 4 more

Abstract read
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In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Tingting Cui *Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Siyi Liu *Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Tingting Wang *Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
Yarui Liu *Department of Pediatric Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
Xinyue Liang *Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Faming ChenGuangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, China.
Mingzhu HuangGuangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, China.
Xiaoling SuDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Tao SongDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Jie SuDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Shidong DengDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Jincun ZhaoDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. zhaojincun@gird.cn.
Fulong YuGuangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, China. yu_fulong@gzlab.ac.cn.
Zhongfang WangDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. wangzhongfang@gird.cn.

Funding

Grand of State Key Laboratory of Respiratory Disease SKLRD-Z-202220Major Project of Guangzhou National Laboratory GZNL2023A01009National Key Research and Development Program of China 2022YFC2604104National Natural Science Foundation of China 82271801National Natural Science Foundation of China 82402059Open Project of State Key Laboratory of Respiratory Disease SKLRD-OP-202206R&D Program of Guangzhou National Laboratory SRPG23-005
6 · The paper itself

Abstract

backgroundDuring the COVID-19 pandemic, diverse vaccine strategies were applied globally, yet most relied on immunogenicity evaluations and bridging trials rather than retrospective assessment through real-world infections. This limited understanding of protective mechanisms under natural variant exposure.

methodsA retrospective cohort study of real-world BA.5 infections was used to analyze the protective efficacy of Ad5-nCoV booster vaccination (A-A). Multi-layered immune profiling was performed, including neutralizing antibodies (NAbs), single-cell BCR sequencing (BCR usage), transcriptomic profiling (RNA-seq), antibody-dependent cellular cytotoxicity (ADCC), natural killer (NK) cell cytotoxicity, and virus-specific T cell immunity. These were integrated to dissect A-A-induced protection mechanisms.

resultsThe A-A conferred 48% effectiveness against symptomatic BA.5 infection (115/239) compared to the three doses of inactivated vaccine (I-I-I), which showed 10% effectiveness (4/39). Specifically, in the A-A group, 52% (124/239) of individuals experienced symptomatic infection, 38% (90/239) had asymptomatic infection, and 10% (25/239) remained uninfected. Compared to I-I-I, A-A induced significantly higher NAbs against BA.5 (GMT = 180 vs. I-I-I GMT = 54) and comparable anti-WT NAbs (GMT = 358 vs. 226), despite lower anti-S IgG levels (GMT = 6441 vs. 12,228) at 2 months post BA.5 infection. Single-cell BCR analysis revealed broader neutralizing antibody clone types in A-A, dominated by IGHV4-39 usage with elevated somatic mutation frequency. Additionally, transcriptomic and functional assays demonstrated an enhanced NK cell-mediated ADCC response and cytotoxicity against K562 target cells in A-A.

conclusionsAd5-nCoV booster vaccination confers enhanced protection against symptomatic BA.5 infection through cross-reactive NAbs with expanded epitope breadth and NK cell-mediated innate immunity enhancement. This retrospective study provides insights into the immunogenicity and molecular mechanisms of two vaccination strategies against real-world BA.5 infection, highlighting Ad5-based technology's efficacy. It provides guidance for future vaccination strategies against emerging Disease X, emphasizing the value of retrospective real-world analyses in vaccine development.

Indexed as

Antibodies, NeutralizingCOVID-19COVID-19 VaccinesKiller Cells, NaturalSARS-CoV-2AdultAgedAntibodies, ViralAntibody-Dependent Cell CytotoxicityFemaleHumansImmunization, SecondaryMaleMiddle AgedRetrospective StudiesAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesAd5-nCoV vaccineBA.5 infectionCross-neutralizing antibodiesNK cell immunityProtective efficacy

Identifiers

PMID41462459
PMCPMC12751559

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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.