Search Results (283)

Respiratory syncytial virus (RSV) remains a leading cause of pneumonia in young children in Mexico and worldwide. To investigate RSV dynamics in Mexico, we conducted a multicenter study from August 2021 to July 2023 in six hospitals across five States, analyzing respiratory samples from children under five years with pneumonia. Multiplex RT-PCR identified 203 RSV-positive cases, of which 123 were RSV-B and 80 RSV-A. Interestingly, 77% of the collected samples showed evidence of coinfection with other respiratory pathogens, with rhinovirus, Haemophilus influenzae, and Streptococcus pneumoniae being the most common. Also, RSV-B dominated in 2021–2022, whereas RSV-A prevailed in 2022–2023, mirroring trends observed in the United States. Sequences of the genes encoding G and F proteins showed that RSV-A lineages were more diverse, with A.D.1, A.D.1.8, and A.D.5.2 being frequently detected. In contrast, nearly all RSV-B sequences belonged to lineage B.D.E.1. Finally, ancestral state inference suggests repeated introductions from the USA and other North American countries, with limited evidence of sustained local circulation. These findings show different trends in RSV circulation between two consecutive seasons and the importance of genomic surveillance to monitor RSV diversity, evaluate vaccine impact, and inform public health strategies in Mexico’s evolving post-pandemic respiratory virus landscape. Full article

Background: The current assessment method of the protective efficacy of adjuvanted vaccines remains slow and labor-intensive, hindered by prolonged immunization protocols and complex assays. Methods: To overcome this bottleneck, we demonstrate that early segregated cellular biomarkers enable rapid prediction of protection, using a respiratory syncytial virus (RSV) pre-fusion F (pre-F) protein model with diverse adjuvants in mice. Results: We identified that germinal center (GC) B cell responses (Days 7 and 9 post-immunization) strongly aligned with protective efficacy, except for Alum, which achieved MF59-level protection despite lower GC responses. Crucially, follicular dendritic cell (FDC) abundance at day 7 universally predicted protection across all adjuvants, including Alum, drastically shortening discovery time and effort from at least 4–6 weeks to within 1 week. Conclusions: FDCs and GC B cells serve as complementary early biomarkers that accurately forecast vaccine efficacy. This approach could potentially reduce the need for prolonged immunization regimens by cellular profiling on days 7–9, offering a modest step toward streamlining adjuvant selection and informing vaccine design. Full article

Background and Objectives: Acute bronchiolitis is a leading cause of hospitalization and morbidity in infants and young children. The COVID-19 pandemic has impacted its epidemiology globally. This study aims to assess changes in bronchiolitis epidemiology in Greece during the period of COVID-19 restrictive measures and after their removal, compared to the pre-pandemic period. Materials and Methods: A retrospective non-interventional study was conducted at a tertiary pediatric hospital, including all children aged 0–24 months hospitalized for bronchiolitis between 1 November 2017 and 30 September 2024. A total of 1505 cases were included. Data were analyzed across seven seasonal periods. Results: Bronchiolitis hospitalizations decreased by 98% in 2020–2021, returned to pre-pandemic levels in 2021–2022, and increased by 58.7% in January 2022–2023. The seasonal distribution shifted earlier in 2021–2022, with a return to pre-pandemic patterns in 2022–2023 and 2023–2024. No shift was observed in the peak age group (1–3 months), although neonatal hospitalizations decreased significantly in 2020–2021 (p = 0.009). RSV-positive cases dropped notably during 2020–2021 (41.2%). There was no change in disease severity across periods, assessed by indirect indicators and the Modified Tal Score. The proportion of bronchiolitis cases among total pediatric admissions increased to 5.6% in 2023–2024, compared to 4.9% in 2022–2023 and 3.9% pre-pandemic (2017–2020). Conclusions: Bronchiolitis epidemiology was significantly impacted by the COVID-19 pandemic in Greece, though disease severity remained unchanged. Ongoing monitoring of bronchiolitis and RSV circulation is crucial particularly with the introduction of maternal RSV vaccination and new monoclonal antibodies to inform prevention strategies and reduce disease burden. Full article

Background: As of 2024, three approved respiratory syncytial virus (RSV) vaccines are licensed for use in adults in the United States: Arexvy™, Abrysvo™, and mRESVIA™. These vaccines are specifically designed to prevent lower respiratory tract disease caused by RSV in adults aged 60 and older. All licensed vaccines rely on stabilized RSV pre-fusion F (pre-F) as the sole antigen. RSV vaccines targeted to the other key RSV surface protein, the G glycoprotein, have been slow to advance because of sequence diversity and a historical association with vaccine-enhanced disease in animal models of infection. The recent development of structure-guided subunit immunogens and immune-modulating adjuvants has renewed interest in RSV G, as the combination of both F and G glycoproteins appears to improve vaccine efficacy over either one individually. RSV G is extensively O-glycosylated, with two mucin-like regions. Methods: This study investigated the effects of manipulation of O-linked glycosylation on a recombinant RSV G vaccine antigen in an RSV/A2 challenge study in BALB/c mice. Conclusions: We found that restricting the O-linked glycosylation on a recombinant RSV G vaccine antigen enhances its immunogenicity and protective efficacy in BALB/c mice. Full article

Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice were subcutaneously immunized with RSV G protein co-administered with varying Cyclosporin A doses, challenged intranasally with RSV, and analyzed for RSV-specific humoral immunity and mechanistic Treg-dependent B-cell responses. Results: We demonstrate that co-administration of CsA with the RSV G protein (G+CsA) dose-dependently boosts RSV-specific IgG and neutralizing antibodies, with selective augmentation of IgG1 and IgG2 subclasses. Mechanistically, G+CsA induces regulatory T cells (Tregs) expressing CD40L and IL-10, which directly promote B-cell activation, proliferation, and plasma cell differentiation. Depletion of Tregs or neutralization of IL-10/CD40L abrogated antibody production, confirming these pathways as critical mediators. Notably, G+CsA-induced Tregs adopt a helper phenotype distinct from conventional Tregs, balancing immune enhancement and homeostasis. Conclusions: CsA demonstrates dual adjuvant properties by enhancing RSV-specific neutralizing IgG titers through Treg-driven B-cell activation, offering a potential strategy to optimize vaccine-induced humoral immunity. Full article

Background/Objectives: Respiratory syncytial virus (RSV) infection can lead to significant complications, particularly among those with underlying cardiovascular and pulmonary complications. Patients with pulmonary hypertension (PH) are susceptible to clinical deterioration triggered by respiratory infections due to their limited cardiopulmonary reserve. This study aimed to assess the risk of hospitalization in RSV-infected adults with and without PH. Methods: We conducted a retrospective cohort study using the research network TriNetX to assess the risk of hospitalization in a cohort of patients with RSV infection, comparing those with and without PH. Propensity score matching was performed for demographic variables and RSV risk factors between the two cohorts. The risk of hospitalization was expressed as an adjusted odds ratio (aOR) with a 95% confidence interval (CI). Results: There were 193,256 patients in the RSV with PH cohort and 2,843,714 in the RSV without PH cohort (all aged >18 years). The mean age of the RSV with PH cohort was 68.2 ± 15.3 years, 50.6% were females, 64% were white, and 64.2% were group 2 PH. The RSV with PH cohort was at an increased risk of hospitalization (aOR 1.89, 95% CI 1.87–1.92, p-value 0.02). There was a significant risk (aOR 1.29, 95% CI 1.27–1.32) for the composite outcome of hospitalization-related complications between the two cohorts. Comorbid conditions (diabetes, cardiovascular disease, chronic lung disease, and chronic kidney disease) increased the risk of hospitalization in the RSV with PH group, with the biggest effect noted with underlying cardiovascular disease. Similarly, those with group 2 PH had a higher risk of hospitalization compared to the other PH groups. Remarkably, all PH groups demonstrated increased hospitalization risk compared to the RSV without PH cohort. Conclusions: We found that patients >18 years of age with PH and RSV infection were at an increased risk of hospitalization, with subsequently higher rates of RSV-infection-related complications. All PH groups had a higher hospitalization risk compared to the RSV without PH cohort, likely denoting PH as an independent risk factor for worse RSV-infection-related outcomes. RSV vaccination, therefore, may benefit all age groups of patients with PH. Full article

In this study, we develop a mathematical model to describe the transmission dynamics of the Respiratory Syncytial Virus (RSV), incorporating the coexistence of two distinct strains. The global stability of the disease-free and endemic equilibria is analyzed. Bifurcation analysis reveals the occurrence of a forward bifurcation. To control the spread of the infection, Pontryagin’s maximum principle is applied within the framework of optimal control theory, considering intervention strategies such as isolation, treatment, and vaccination. A detailed evaluation of the effectiveness of these control strategies is conducted for a specific population based on a nonlinear optimal control model. Moreover, a cost-effectiveness analysis is performed to identify the most economically viable intervention. The findings indicate that, among the studied interventions, isolation is the most cost-effective strategy for reducing RSV prevalence. The model is numerically solved using the fourth-order Runge–Kutta method, coupled with the forward–backward sweep algorithm, to assess the impact of various control combinations on the transmission dynamics of RSV. Full article

Elite athletes are at an increased risk of infections due to behavioral and social factors and frequent travel. Furthermore, heavy physical exercise may induce immunosuppression. Most infections in athletes are acute respiratory illnesses (ARIs) with various viral etiologies. Although athletes, as young, healthy adults, are not at risk for severe infections, a prolonged ARI may ruin a training season or a significant competition or may spread within a sports team. Many common infections are vaccine-preventable. This Opinion advocates for more active vaccination among athletes, although some of the vaccines are not officially recommended for young adults. New respiratory syncytial virus (RSV) protein vaccines are effective and well-tolerated. Yearly influenza and COVID-19 vaccinations are strongly recommended. Conjugated polyvalent pneumococcal vaccines are recommended because they may also induce protection against respiratory viral infections. Pertussis and measles outbreaks are occurring globally. The history of measles vaccination should be reviewed, and consideration should be given to a pertussis booster vaccination (Tdap). A recombinant vaccine can effectively prevent herpes zoster. The vaccination of elite athletes is a cost-effective and powerful tool, but it is currently underused. The sports medicine community can address vaccine hesitancy among athletes by listening to their concerns and giving accurate information. Full article

Since the emergence of SARS-CoV-2, the interplay of human behavior, environmental factors, viral evolution, and public health interventions has resulted in unexpected changes in the timing, intensity, and geography of respiratory virus outbreaks. For example, respiratory syncytial viruses (RSV) exhibited a surge during atypical summer months in several countries. Influenza, on the other hand, nearly vanished in the early years of the pandemic, but returned with unusual strength and altered seasonal patterns. Concurrently, new variants of concern in coronaviruses have demonstrated increased airborne transmissibility, greater resilience to environmental conditions, and the ability to evade both natural and vaccine-induced immunity. In this review article, we have synthesized the current understanding of the aerobiology of respiratory infectious viruses, with a particular emphasis on the paradoxical trends observed in recent years. We examined various aspects, including viral morphology and environmental survivability, shifts in seasonality, the drivers of mutation and resistance, and the impact of environmental and climatic factors. Key issues we explored include viral morphology adaptation in response to airborne selective pressures and climate variability influence on the ecology of airborne viruses. Lastly, we investigated future risks and proposed an interdisciplinary framework for monitoring and mitigating airborne viral threats in an ever-changing world. Full article

Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to control these diseases effectively. This review aimed at providing insights on challenges, efforts, impacts, and opportunities for the future related to vaccination against respiratory viral infections in Africa. Methods: This narrative review synthesizes the peer-reviewed literature and global health reports to examine vaccination efforts against respiratory viruses in Africa. The analysis focuses on disease burden, vaccine coverage, barriers to uptake, enabling factors, progress in local vaccine production, and strategies for integrating vaccines into national immunization programs (NIPs). Results: Respiratory vaccines have significantly reduced hospitalizations and mortality among high-risk groups in African countries. Nonetheless, key challenges, including limited cold chain capacity, vaccine hesitancy, donor-reliant supply chains, and under-resourced health systems, continue to undermine vaccine delivery. Successful interventions include community mobilization, use of mobile health technologies, and leveraging existing immunization platforms. Emerging initiatives in local vaccine manufacturing, including Rwanda’s modular mRNA facility and Senegal’s Institut Pasteur, signal a shift toward regional self-reliance. Conclusions: Maximizing the impact of respiratory vaccines in Africa requires a multifaceted strategy: integrating vaccines into NIPs, strengthening domestic production, expanding cold chain and digital infrastructure, and addressing sociocultural barriers through community-driven communication. These efforts are essential to achieving vaccine equity, health resilience, and pandemic preparedness across the continent. Full article

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule. Full article

Respiratory syncytial virus (RSV) remains a leading cause of acute lower respiratory tract infections globally, particularly affecting infants, older adults, and immunocompromised individuals. While recent advances in prophylaxis, such as long-acting monoclonal antibodies and maternal immunization, offer promise for prevention, therapeutic options for active infection remain limited. Severe RSV disease is often driven not solely by viral replication but by dysregulated host immune responses, including excessive cytokine production, T helper type 2 (Th2) and T helper type 17 (Th17) cell polarization, and impaired interferon signaling. RSV has evolved sophisticated immune evasion strategies, such as inhibition of dendritic cell maturation, degradation of signal transducer and activator of transcription 2 (STAT2) via nonstructural proteins 1 and 2 (NS1/NS2), and interference with pattern recognition receptor signaling, particularly Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. These mechanisms result in attenuated innate immune responses and defective adaptive immunity, contributing to viral persistence, immunopathology, and recurrent infections. Moreover, age-dependent vulnerabilities, such as immune immaturity in infants and immunosenescence in older adults, exacerbate disease severity. Excessive immune activation leads to bronchiolitis, airway remodeling, and long-term sequelae including wheezing and asthma. Emerging immunomodulatory therapies aim to restore immune balance, targeting cytokines (e.g., interleukin-6 [IL-6], interleukin-1 beta [IL-1β]), the Janus kinase–signal transducer and activator of the transcription (JAK-STAT) pathway, or inflammasome activity. Host-directed therapies and direct-acting antivirals are also under investigation. A better understanding of RSV–host immune interactions is critical for optimizing therapeutic strategies and designing effective vaccines. This review synthesizes current knowledge on RSV immunopathogenesis and highlights immunomodulation as a promising frontier for therapeutic intervention. Full article

Background/objectives: This was a post hoc analysis of safety data across the bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine clinical trial development program. Methods: Data from eight clinical trials in 46,913 immunocompetent adults who received RSVpreF or placebo were analyzed. Local reactions and systemic events were assessed among non-pregnant ≥18-year-olds (n = 9517); adverse events (AEs) among pregnant and non-pregnant 18–59-year-olds (n = 9238); and vaccine-related AEs among non-pregnant ≥18-year-olds (n = 39,314). Post-marketing data in non-pregnant adults were considered. Results: Local reactions and systemic events were reported more frequently in RSVpreF versus placebo recipients; injection site pain was the most common local reaction (RSVpreF, 18.9%; placebo, 7.4%), and fatigue (23.5%; 18.4%) and headache (19.5%; 15.0%) were the most common systemic events. Percentages of AEs within 1 month after vaccination were similar across groups (RSVpreF, 12.8%; placebo, 13.1%); severe AEs were reported in ≤1.5% of participants. Differences in percentages of individuals reporting vaccine-related AEs between the RSVpreF and placebo groups were <0.2% for all related AEs. Serious AEs throughout the study were reported in ≤14.0% (RSVpreF, 12.6%; placebo, 14.0%). No atrial fibrillation, Guillain-Barré syndrome, or acute polyneuropathy cases were reported. The AE data from post-marketing data sources were consistent with the safety profile from the clinical trial program, with no new safety concerns. Conclusions: Integrated data demonstrated that RSVpreF was well tolerated with a favorable safety profile in non-pregnant and pregnant adults. Ongoing surveillance through real-world use and clinical trial experience continue to support the safety profile of RSVpreF. ClinicalTrials.gov: NCT03529773/NCT04071158/NCT04785612/NCT05035212/NCT05096208/NCT05842967/NCT04032093/NCT04424316. Full article

Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I² = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article