Daily Respiratory Research Analysis
Analyzed 61 papers and selected 3 impactful papers.
Summary
Analyzed 61 papers and selected 3 impactful articles.
Selected Articles
1. Non-propagating RNA virus-vectored HA/NA vaccine prevents shedding of antigen-drifted H1N1 influenza virus in pigs.
A single-cycle VSV vector encoding HA and NA induced robust cross-protective immunity in pigs, eliminating shedding of a drifted H1N1 challenge virus and showing N1-directed activity against avian H5N1 in vitro. Homologous VSV prime-boost performed comparably to a heterologous VSV/LAIV regimen in the upper respiratory tract.
Impact: Demonstrates a practical vaccine platform that targets both HA and NA to prevent transmission-relevant shedding of drifted influenza, addressing vaccine mismatch and zoonotic threats.
Clinical Implications: Supports advancing HA+NA single-cycle VSV vaccines to human trials with transmission endpoints (viral shedding) and encourages inclusion of NA to broaden cross-protection, potentially mitigating seasonal mismatches and zoonotic spillover.
Key Findings
- Single intramuscular immunization with VSV-HA/NA elicited high H1N1-neutralizing titers and potent N1 sialidase inhibition.
- Homologous VSV or heterologous LAIV boost enhanced inhibition against the drifted A/Victoria/2570/2019 (H1N1) strain.
- Vaccination induced N1-specific antibodies that inhibited avian N1 and suppressed bovine-derived H5N1 replication in vitro.
- Post-challenge, vaccinated pigs had no detectable virus shedding, unlike controls.
- Homologous VSV prime-boost matched VSV/LAIV in upper respiratory tract protection.
Methodological Strengths
- Relevant large-animal (porcine) challenge model with transmission-relevant endpoint (viral shedding).
- Evaluation of both homologous and heterologous boost regimens with functional NA inhibition assays.
Limitations
- Preclinical animal study; human safety, immunogenicity, and durability are untested.
- Duration of protection and breadth against diverse clades beyond those tested remain to be defined.
- Potential impact of pre-existing anti-VSV immunity was not addressed.
Future Directions: Conduct phase I/II trials assessing safety, immunogenicity, durability, and reduction of viral shedding; optimize NA antigen design for breadth; evaluate efficacy against zoonotic H5Nx; address manufacturing and deployment logistics.
Seasonal influenza viruses evade immunity through antigenic drift, enabling escape from inhibitory antibodies targeting hemagglutinin (HA) and neuraminidase (NA). In this study, we evaluated a non-propagating vesicular stomatitis virus (VSV) vector encoding HA and NA antigens of A/Hamburg/4/2009 (H1N1) in a porcine animal model to assess induction of cross-reactive immunity. A single intramuscular immunization elicited high titers of H1N1-neutralizing antibodies and potent N1-sialidase inhibition. A boost with the same single-cycle VSV-vectored H1/N1 antigens or with a live-attenuated influenza vaccine (LAIV) enhanced inhibitory activity against the antigen-drifted A/Victoria/2570/2019 (H1N1) strain. Vaccination induced N1-specific antibodies that also inhibited avian N1 sialidase and suppressed replication of a bovine-derived H5N1 virus in vitro. Following nasal challenge with a 6:2 reassortant virus encoding drifted HA and NA antigens, vaccinated pigs showed no detectable virus shedding, whereas control animals shed infectious virus. Homologous prime-boost vaccination with the VSV-vectored H1/N1 antigens conferred protection comparable to the heterologous VSV/LAIV regimen in the upper respiratory tract. These findings demonstrate that a single-cycle VSV vector encoding both HA and NA induces cross-protective immunity against antigen-drifted influenza viruses, reduces the risk of vaccine mismatch, and may limit infection by zoonotic H5N1 viruses.
2. Regulation of neuronal invasion of small cell lung cancer by STMN2/β-alanine-controlled metabolic reprogramming.
Perineural invasion is validated as an independent adverse prognostic factor in SCLC, and a neural–STMN2–β-alanine axis is shown to drive neural invasion through metabolic reprogramming. In vivo, STMN2 loss reduces neural invasion, reversible with β-alanine supplementation, revealing a targetable metabolic vulnerability.
Impact: Identifies a previously unrecognized metabolic mechanism for neural invasion in SCLC and proposes actionable targets (STMN2 and β-alanine metabolism) for anti-invasion therapies.
Clinical Implications: Supports incorporating PNI into risk stratification and motivates development of inhibitors targeting β-alanine metabolism or STMN2 to mitigate neural invasion and potentially improve outcomes.
Key Findings
- Perineural invasion is an independent adverse prognostic factor in a surgical SCLC cohort.
- Neural microenvironment upregulates STMN2 in SCLC cells.
- STMN2 activates β-alanine metabolism dose-dependently, increasing intracellular β-alanine and tumor invasiveness.
- In vivo, STMN2 knockdown suppresses neural invasion; β-alanine supplementation reverses this effect.
- Defines a neural–STMN2–β-alanine axis as a metabolic driver of PNI and a therapeutic vulnerability.
Methodological Strengths
- Integration of a clinical prognostic cohort with in vitro and in vivo mechanistic validation.
- Rescue experiments (β-alanine supplementation) establish causality of the metabolic pathway.
Limitations
- Clinical cohort size and detailed adjustment variables are not specified in the abstract.
- Therapeutic targeting was not tested with pharmacologic inhibitors.
- Generalizability to advanced, non-surgical SCLC remains to be established.
Future Directions: Develop and test pharmacologic inhibitors of β-alanine synthesis/transport or STMN2 modulation; validate STMN2 and β-alanine signatures as biomarkers of PNI risk in larger, multi-center cohorts; evaluate impact on metastasis and survival.
Small cell lung cancer (SCLC) exhibits a high incidence of perineural invasion (PNI), a clinical feature associated with poor prognosis. Here, we establish PNI as an independent adverse prognostic factor in a surgical SCLC cohort. We further show that the neural microenvironment upregulates stathmin-2 (STMN2) in SCLC cells. STMN2, in a concentration-dependent manner, activates the β-alanine metabolic pathway, leading to intracellular β-alanine accumulation, which enhances tumor cell migration and invasion. In vivo, STMN2 knockdown suppresses neural invasion, an effect reversible upon β-alanine supplementation. This work defines a neural-STMN2-β-alanine-invasion axis that drives PNI in SCLC, providing mechanistic insights and highlighting a promising metabolic vulnerability for therapeutic intervention.
3. Paternal snus use in puberty and increased risk for asthma and allergies in offspring: a RHINE/RHINESSA two-generation study.
In Swedish RHINE/RHINESSA data (n=1090 father–offspring pairs), paternal snus initiation during puberty was associated with higher risks of offspring allergic asthma, chronic bronchitis, and eczema, independent of paternal and offspring smoking. Snus initiation after puberty showed no consistent associations, supporting puberty as a sensitive exposure window.
Impact: Provides human evidence for intergenerational respiratory risk linked to paternal nicotine exposure during puberty, informing prevention strategies that include preconception health for males.
Clinical Implications: Clinicians should counsel adolescent males and prospective fathers regarding nicotine products (e.g., snus) as potential intergenerational risk factors for asthma and allergies in offspring; public health policies may target puberty to prevent harmful exposures.
Key Findings
- Among 1090 father–offspring pairs, paternal snus initiation during puberty (n=89) was associated with higher risk of offspring allergic asthma (OR 1.42, 95% CI 1.02–1.97).
- Increased risks were also observed for chronic bronchitis (OR 2.17, 95% CI 1.04–4.54) and eczema (OR 1.45, 95% CI 1.27–1.65).
- Snus initiation after puberty showed no consistent associations with offspring outcomes.
- Results were robust after adjusting for paternal and offspring smoking and excluding offspring snus users.
Methodological Strengths
- Two-generation design with mixed-effects logistic regression and adjustment for key confounders.
- Sensitivity analyses excluding offspring snus users supported robustness.
- Clear temporal stratification of exposure (puberty vs post-puberty initiation).
Limitations
- Observational design cannot establish causality; residual confounding is possible.
- Relatively small number of fathers initiating snus during puberty (n=89) limits precision.
- Generalizability may be limited to Swedish populations and cultural contexts.
Future Directions: Replicate findings in larger, diverse cohorts; investigate epigenetic mechanisms in sperm; evaluate other nicotine products (e.g., e-cigarettes) and dose–response; design targeted public health interventions during puberty.
BACKGROUND: Evidence suggests that a father's smoking in puberty may adversely impact respiratory health in offspring, possibly through epigenetic changes in germ cells. This study investigates whether snus use starting in or after puberty influences respiratory health in future offspring. METHODS: We analysed Swedish data from RHINE (Respiratory Health in Northern Europe) parents and RHINESSA (Respiratory Health in Northern Europe, Spain and Australia) offspring by using mixed-effect logistic regression to assess the links between paternal snus initiation around puberty and offspring asthma, chronic bronchitis, rhinitis, and eczema, adjusting for paternal and offspring smoking. RESULTS: We identified 1090 offspring-father pairs. The offspring's median age was 29 years (17-51) and 55% were women. The maternal line (n = 1421) was not analysed, as <1% of mothers used snus in puberty. The offspring of fathers starting snus use in puberty (n = 89) had a higher risk of current allergic asthma [odds ratio (OR) 1.42; 95% confidence interval (CI) 1.02-1.97], at least three asthma symptoms with allergy (OR 1.13; 95% CI 1.10-1.21), chronic bronchitis (OR 2.17; 95% CI 1.04-4.54), and eczema (OR 1.45; 95% CI 1.27-1.65). Fathers' snus use starting after puberty (n = 252) showed no consistent associations with offspring outcomes. The effect estimates were consistent after excluding offspring using snus in puberty. CONCLUSION: Paternal snus use starting in puberty was associated with a higher risk of asthma and other respiratory and allergic symptoms in offspring. These findings support the hypothesis that exposures in puberty may impact future generations' respiratory health, possibly through epigenetic changes. This highlights the need for research on exposures during this period and actions to prevent habits that could negatively impact future offspring's health.