Daily Respiratory Research Analysis
Analyzed 68 papers and selected 3 impactful papers.
Summary
Analyzed 68 papers and selected 3 impactful articles.
Selected Articles
1. Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses.
Post-2019 influenza B viruses evade many previously reported head-directed bnAbs via fixation of K136E in Victoria-lineage HA. Two human bnAbs (CAV-CF22, CAV-CH76), isolated after routine quadrivalent vaccination, neutralize both Victoria and Yamagata lineages in vitro and protect in vivo by inserting HCDR3 into the receptor-binding site to mimic sialic acid, highlighting a conserved, drift-resilient epitope.
Impact: Defines a structural solution to recent IBV antigenic drift and provides bnAbs that inform resilient vaccine and antibody designs.
Clinical Implications: Focus future IBV vaccines and therapeutic antibodies on conserved RBS-mimicking epitopes to maintain breadth despite K136E drift. Surveillance should monitor K136E and similar head mutations to guide strain selection.
Key Findings
- Post-2019 Victoria-lineage HA fixed K136E, abrogating binding of many previously characterized head-directed bnAbs.
- Two human bnAbs (CAV-CF22, CAV-CH76) neutralized both Victoria and Yamagata lineages in vitro and protected in vivo.
- High-resolution structures showed HCDR3 insertion into the RBS, sterically mimicking sialic acid, explaining breadth.
- Conserved epitope residues underpin resilience to recent IBV drift and inform vaccine/antibody design.
Methodological Strengths
- Integrated phylogenetic analysis with high-resolution structural biology to map drift and epitope conservation.
- Combined in vitro neutralization breadth assays with in vivo protection studies.
- Mechanistic elucidation of RBS mimicry by HCDR3 explaining cross-lineage activity.
Limitations
- Clinical efficacy of these bnAbs in humans was not tested.
- Sample size and donor characteristics for antibody isolation were not detailed, limiting generalizability.
- Durability of protection and potential for future escape mutations require longitudinal assessment.
Future Directions: Advance RBS-focused immunogen design and evaluate clinical translation of CAV-CF22/CAV-CH76-like antibodies; enhance global surveillance for HA head mutations like K136E.
Antigenic drift in hemagglutinin (HA) enables influenza viruses to escape host immunity. Elucidating molecular features of antigenic drift is essential for updating seasonal vaccines and pandemic preparedness. Here, we found that influenza B viruses (IBVs) isolated after 2019 escaped neutralization by several previously identified broadly neutralizing monoclonal antibodies (bnAbs). Meanwhile, we identified two IBV bnAbs, CAV-CF22 and CAV-CH76, isolated via quadrivalent vaccine. They exhibited broad neutralizing activity against Victoria- and Yamagata-lineage viruses in vitro and protected in vivo against contemporary Victoria and Yamagata strains. Phylogenetic and structural analysis revealed fixation of K136E in post-2019 Victoria HA, disrupting epitopes targeted by most previously characterized head-directed IBV-monoclonal antibodies (mAbs). High-resolution structures reveal that, rather than engaging K136, CAV-CF22 and CAV-CH76 insert HCDR3 into the receptor-binding site (RBS) to sterically mimic sialic acid. The conservation of epitope residues underlies the antibodies' broad neutralizing activity against IBV and informs antibody- and vaccine-design strategies that are resilient to recent IBV drift.
2. Efficacy and long-term engagement of a WeChat-integrated modality versus a traditional quitline on smoking cessation in China: a randomised controlled trial.
In a preregistered, open-label RCT of 460 adult smokers, a multi-component WeChat-integrated program achieved higher biochemically verified 7-day abstinence at 1 month than a traditional quitline (41.5% vs 27.9%; RR 1.49). Engagement with the mini-program declined after 3 months, yet higher early usage dose-dependently predicted greater abstinence up to 12 months.
Impact: Demonstrates superior short-term efficacy of a scalable, theory-guided digital cessation modality in China with biochemical verification and identifies early engagement as a predictor of long-term abstinence.
Clinical Implications: Healthcare systems can integrate multi-component social-media-based cessation tools as effective alternatives or adjuncts to quitlines, prioritize strategies to boost early engagement, and plan for maintenance features to counter engagement decay.
Key Findings
- WeChat-based intervention yielded higher 1-month biochemically verified 7-day PPA than quitline (41.5% vs 27.9%; RR 1.49; 95% CI 1.14–1.95; P=0.004).
- Engagement with the mini-program fell from 99.0% at 1 month to 6.7% at 8 months.
- Greater early usage in the first 3 months was dose-dependently associated with higher 3-, 6-, and 12-month abstinence.
- All participants received nicotine gum, and analyses followed a modified intention-to-treat approach.
Methodological Strengths
- Preregistered randomized controlled trial with biochemical verification of abstinence.
- Modified intention-to-treat analysis and prespecified multi-timepoint follow-up to 12 months.
Limitations
- Open-label design with potential expectancy and performance biases.
- Engagement markedly declined after 3 months; generalizability may be limited to digitally engaged urban populations.
Future Directions: Test maintenance strategies to sustain engagement beyond 3 months, evaluate cost-effectiveness and scalability in diverse regions, and compare with pharmacotherapy-augmented and hybrid cessation models.
BACKGROUND: Digital health interventions offer a promising opportunity to innovate traditional cessation services. Multi-component digital approaches show potential for greater effectiveness than traditional methods, though optimal integration strategies and engagement dynamics are still unclear. This study evaluated 'Way to Quit' (WQ)-a theory-guided, integrated modality based on WeChat (a popular social media platform)-compared with a quitline, with particular attention to long-term engagement and its impact on abstinence. METHODS: A two-arm, open-label, randomised controlled trial was conducted in Beijing, China, from December 1, 2022 to June 13, 2024. We recruited adult smokers intending to quit within one month via online advertisements. Participants were randomly assigned (1:1; using various block sizes) to either a multicomponent WeChat-based intervention (WQ)-integrating a mini-programme (application-like service), a chat group (peer support) and an official account (information channel)-or telephone counselling (Quitline), both lasting four weeks (one pre-quit week and three post-quit weeks). All participants received a four-week supply of nicotine gum by mail for on-demand use. Follow-up assessments were completed at one, three, six, and twelve months after the initiation of the intervention via telephone or online. The primary outcome was biochemically verified 7-day point prevalence abstinence (PPA) at one month. Analyses followed a modified intention-to-treat (mITT) approach. RESULTS: A total of 460 adult smokers were enrolled and randomised (WQ: n = 230; Quitline: n = 230), with 414 included in the mITT analysis (WQ: 195; Quitline: 219). At one month, biochemically verified 7-day PPA was 41.5% in the WQ group and 27.9% in the Quitline group (RR, 1.49; 95% CI, 1.14-1.95; P = 0.004). Mini-programme engagement peaked initially but declined after three months, from 99.0% in one month to 6.7% in eight months. Greater usage during the first three months was dose-dependently associated with higher long-term abstinence rates (3-, 6-, and 12-month 7-day PPA), with all P CONCLUSIONS: The WQ modality showed superior short-term efficacy compared with the quitline, supporting its potential as an alternative or adjunct to traditional cessation services. Although long-term engagement remained challenging, early engagement intensity within the first three months strongly predicted twelve-month abstinence. TRIAL REGISTRATION: The trial was preregistered at Chinese Clinical Trial Registry Identifier (https://www.chictr.org.cn/bin/project/edit?pid=179013, ID: ChiCTR2200066427). Registration date: December 5, 2022.
3. Genome-wide association study reveals two novel genetic loci associated with chronic lung allograft dysfunction.
In the first GWAS of lung transplantation, genotyping 392 donor–recipient pairs identified two recipient loci associated with CLAD and confirmed the deleterious role of HLA allelic/epitopic mismatches, primarily class I. Donor genotypes and donor–recipient non-HLA mismatches were not significantly associated, underscoring recipient genetics and HLA matching as key drivers.
Impact: Provides foundational genomic insights into CLAD pathogenesis and quantifies the central role of HLA class I mismatches, informing risk stratification and donor–recipient matching strategies.
Clinical Implications: Transplant programs may refine risk models by incorporating recipient genetic risk loci and detailed HLA epitope matching, prioritizing class I compatibility to mitigate CLAD risk.
Key Findings
- Two independent recipient genetic loci were associated with CLAD, including a protective allele enriched in non-CLAD recipients.
- HLA allelic and epitope mismatches, predominantly class I, were deleterious for CLAD risk (p=0.004).
- No significant associations were detected for donor genotypes or donor–recipient non-HLA mismatches after adjustment.
Methodological Strengths
- Multicenter cohort with 392 donor–recipient pairs genotyped and ~4.5M SNPs tested.
- Multivariable logistic regression with correction for age, sex, initial disease, and genetic ancestry; distinct donor, recipient, and mismatch analyses including HLA-centric models.
Limitations
- Sample size is modest for GWAS, limiting power and precision; replication is required.
- Abstract truncation precludes reporting exact p-values for the identified loci; effect sizes and functional validation are pending.
Future Directions: Replicate and fine-map recipient loci, perform functional studies to elucidate mechanisms, and integrate epitope-level HLA matching with genomic risk in prospective allocation and surveillance.
BACKGROUND: Chronic lung allograft dysfunction (CLAD) leads to declining respiratory function and high mortality, representing the main barrier to long-term survival in lung transplantation (LT). We performed the first genome-wide association study (GWAS) investigating donor's and recipient's genetic factors associated with CLAD. METHOD: We genotyped 392 donor-recipient pairs from the multicentric Cohort in Lung Transplantation. We tested 4.5 million SNPs for association with CLAD using multivariable logistic regression models corrected for age, sex, initial disease and genetic ancestry. Three levels of explanatory variables were separately considered to conduct GWAS: donors-only, recipients-only, and donor-recipient mismatches. We also ran HLA-centric analyses using the same models. RESULTS: Our analysis confirmed the deleterious impact of HLA allelic and epitopic mismatches on CLAD risk, mostly driven by class I HLA (p=0.004). No significant associations with CLAD were found for donors' genotypes or donor-recipient non-HLA mismatches. We highlighted two independent recipient's loci associated with CLAD, including one protective signal (0.39 in CLAD vs 0.66 in non-CLAD recipients, p-value=5.05x10 CONCLUSION: This first LT GWAS revealed two candidate loci from the recipient's genome, both biologically relevant for CLAD pathogenesis. Our study calls for larger LT genomic initiatives to increase power for signal discovery.