Search Results (236)

Background/Objectives: The combination of a hemagglutinin antigen (HA)-based inactivated influenza vaccine (IIV; Fluarix^® Tetra; GlaxoSmithKline) with a nucleoprotein (NP)-based vaccine, such as OVX836, should increase the efficacy of influenza vaccines since it leverages two complementary immunological mechanisms: HA antibodies targeting the virus envelope and neutralizing it, and an NP cell-mediated immune (CMI) response destroying infected cells. Methods: This was a randomized, double-blind, Phase 2a study (ClinicalTrials.gov NCT05284799) including three groups of 60 healthy subjects (18–55 years old) receiving either IIV + placebo, IIV + OVX836 (480 µg), or OVX836 + placebo intramuscularly and concomitantly into the same deltoid muscle. The endpoints were reactogenicity, safety, and immunogenicity (hemagglutination inhibition assay [HAI], anti-NP immunoglobulin G [IgG], and NP-specific cell-mediated immunity [CMI]). Results: The co-administration of IIV + OVX836 was safe and well-tolerated. The HAI response was strong and similar in the two IIV groups with no interference of OVX836. The humoral anti-NP IgG and NP-specific CMI responses to OVX836 were strong in the two OVX836 groups, and no major interference of IIV was observed. Conclusions: This study supports further clinical development of OVX836 as a combined IIV/OVX836 seasonal vaccine capable of inducing robust and complementary HAI and CMI NP-specific responses. Full article

Vaccination plays a pivotal role in the control and prevention of animal infectious diseases. However, no efficient and safe universal vaccines are currently registered for major pathogens such as influenza A virus, foot-and-mouth disease virus (FMDV), simian immunodeficiency virus (SIV), and small ruminant lentiviruses (SRLV). Here, we review the development of Sendai virus (SeV) vectors as a promising vaccine platform for animal diseases. Recombinant SeV vectors (rSeVv) possess several key features that make them highly suitable for developing vaccination strategies: (1) SeV has exclusively cytoplasmic replication cycle, therefore incapable of transforming host cells by integrating into the cellular genome, (2) rSeVv can accommodate large foreign gene/s inserts (~5 kb) with strong but adjustable transgene expression, (3) can be propagated to high titers in both embryonated chicken eggs and mammalian cell lines, (4) exhibits potent infectivity across a broad range of mammalian cells from different animals species, (5) undergo transient replication in the upper and lower respiratory tracts of non-natural hosts, (6) has not been associated with disease in pigs, non-humans primates, and small ruminants, ensuring a favorable safety profile, and (7) induce a robust innate and cellular immune responses. Preclinical and clinical studies using rSeVv-based vaccines against influenza A virus, FMDV, SIV, and SRLV have yielded promising results. Therefore, this review highlights the potential of rSeVv-based vaccine platforms as a valuable strategy for combating animal viruses. Full article

Influenza viruses pose a significant threat to human health, and vaccination remains the most cost-effective and efficient strategy for controlling outbreaks. This review first introduces the molecular characteristics of influenza A virus (IAV) and examines how conserved epitopes contribute to overcoming its high variability, laying the foundation for broadly protective vaccine design. Different vaccine platforms are then categorized and analyzed through representative examples to highlight their research significance and application potential. The discussion further extends to the role of adjuvants in modulating immune responses, with a focus on how their optimization enhances vaccine efficacy. We explore future directions in vaccine design, highlighting the synergistic potential of conserved epitope targeting and adjuvant improvement in advancing the next generation of influenza vaccines. Full article

Influenza B, a globally prevalent respiratory virus, particularly affects children, the elderly, and individuals with chronic diseases. This retrospective single-center study analyzed long-term epidemiological trends using 23,284 PCR test results from Dankook University Hospital, Cheonan-si, Republic of Korea, from 2007 to 2024. The data included inpatients and outpatients who presented with respiratory symptoms and underwent multiplex PCR testing. Unlike previous studies focusing on short-term outbreaks, this study examines extended trends and emerging seasonal patterns. Positivity rates were statistically analyzed by year, season, sex, age group, and the impact of COVID-19 (2020–2022). Significant annual differences (p < 0.001) occurred, with peaks in 2012 and 2018 and a sharp decline during 2020–2022. Children exhibited the highest positivity rate (2.40%), significantly higher than that of adults (2.24%) and the elderly (1.79%) (p < 0.05). Infections peaked in the winter (2.98%) and spring (3.95%), contrary to the belief that Influenza B peaks in winter only. Females had a higher positivity rate (2.13%) than males (1.70%) (p = 0.017). These findings provide novel insights into Influenza B epidemiology, emphasizing the need for prevention strategies beyond winter. The secondary spring peak suggests extending vaccination to early spring may improve influenza control, particularly among high-risk groups. Full article

Background: Many vaccines are safe and recommended during pregnancy. Transmission of maternal antibodies produced in large quantities after vaccination protects the neonate in the first months of life, until the first vaccinations in infancy. In Poland, at the time of the study, influenza, pertussis, and COVID-19 vaccines were recommended during pregnancy. Methods: The authors performed a survey study in a group of 591 post-partum women. They were asked about the safety of pertussis, influenza and COVID-19 vaccines in pregnancy. Data regarding vaccination during pregnancy according to Polish recommendations in relation to the type of vaccine were also analysed. Results: Although 50% of patients reported that, in their opinion, the pertussis vaccine is safe and recommended during pregnancy, only 17% were vaccinated. Similar results authors obtained regarding the influenza vaccine (51% and 6%, respectively). The highest knowledge and compliance with recommendations correlation to the education level was observed in women with college and university education: 65% of them thought that pertussis vaccine is safe and recommended during pregnancy; 27% of them were vaccinated; 63% of them reported that they know that influenza vaccine is recommended during pregnancy and 9% were vaccinated. In a group with the lowest education, 14% reported that the pertussis vaccine is recommended as well as 24%-influenza vaccine. No patient in this group was vaccinated during pregnancy. Conclusions: Low compliance of pregnant women was confirmed in our study, and the desperate necessity of patients’ education regarding the safety of recommended vaccines is warranted. We showed that even patients who know that the vaccine is recommended do not receive vaccination, and the lower the education level, the lower the compliance. Full article

Background/Objectives: Vaccination remains the most effective means of preventing influenza virus infections. However, the continuous antigenic drift and shift of influenza viruses lead to a reduced efficacy of the existing vaccines, necessitating vaccines capable of broad protection. Methods: To address this, we developed a modular vaccine strategy pairing a clinical-stage adjuvanted recombinant hemagglutinin (HA) vaccine (SCVC101) with OMN, a heptameric nanoparticle displaying conserved influenza A virus T-cell epitopes from nucleoprotein (NP) and matrix 2 ectodomain (M2e). Results: OMN induced cross-reactive M2e-specific antibodies, binding to diverse influenza A subtypes. Critically, the co-administration of OMN with SCVC101 enhanced cellular immunity and cross-protection without diminishing HA-induced humoral responses. Conclusions: This dual-antigen delivery system enables annual HA component updates, aligned with WHO recommendations, while the conserved OMN nanoparticle acts as a universal booster, leveraging existing production infrastructure. This approach offers a promising strategy for improving the influenza vaccine’s efficacy against emerging viral variants. Full article

Background: A decrease in governmental vaccination initiatives and diminishing public enthusiasm for vaccines could jeopardize vaccine uptake, potentially endangering those who are most at risk. In this survey study, we evaluated the current acceptance rates of the newly developed monovalent XBB1.5-adapted COVID-19 vaccine among kidney transplant recipients and dialysis patients in Austria and Israel and identified factors influencing vaccine acceptance. Methods: The survey involved a total of 656 patients aged 18 and older and was carried out from 20 November to 21 December 2023, at the Medical University of Vienna, Austria and the Rabin Medical Center in Petah Tikva, Israel. Logistic regression analysis was used to explore the relationships between vaccine acceptance and variables such as age, gender, country, past COVID-19 infection status and severity, renal replacement therapy, education level, and willingness to receive the annual flu vaccine. Results: The survey showed that 54% of patients in Austria and 63% in Israel expressed acceptance of the modified XBB1.5-adapted COVID-19 vaccine. The main hesitancy was due to concerns about potential side effects, with 44% in Austria and 53% in Israel expressing apprehension. A willingness to receive the influenza vaccine, older age in Austria, and kidney transplant status in Israel were key predictors of greater COVID-19 vaccine acceptance. Conclusions: This study showed that more than 50% of our kidney transplant recipients and dialysis patients were willing to receive the adapted COVID-19 vaccine. Yet, vaccine hesitancy remained a significant barrier even among these high-risk groups, despite the availability of an updated COVID-19 vaccine targeting the Omicron subvariant XBB1.5. Full article

The N-terminal ectodomain of the influenza A M2 protein is a target for universal influenza vaccine development and novel antiviral strategies. Despite the significance of this domain, it is poorly understood and most structural studies of the M2 protein have disregarded the N-terminal ectodomain in their analyses. Here, we report conformational properties and describe insights into the membrane topology of sites along the N-terminal ectodomain. Full-length M2 protein is embedded in lipid bilayer nanodiscs and studied using site-directed spin labeling electron paramagnetic resonance spectroscopy. Results are consistent with a turn in the middle of the ectodomain that changes in proximity to the membrane surface upon the addition of cholesterol or the antiviral drug rimantadine. Similarly to other domains of M2 protein, lineshape analysis suggests that the N-terminal ectodomain can adopt multiple conformations. Full article

Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of universal vaccine research due to its cross-protective potential. Additionally, Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are recognized as important protective immune mechanisms. This study evaluated IgG responses to the HA head, stem, and LAH regions and assessed cross-reactive potential through neutralization, ADCC, and ADCP assays. Methods: IgG responses to the HA head, stem, and LAH regions were measured in vaccinated individuals. Functional assays were conducted for neutralization, ADCC, and ADCP to evaluate the association between antibody levels and immune function. Results: The results showed that HA head-specific IgG increased significantly after vaccination in 50 individuals, whereas stem-specific IgG increased by 72% and LAH-specific IgG by 12–14%. Among the induced antibody subclasses, IgG1 was predominantly increased. Neutralization titers were detected in viruses of the same strain as the vaccine strain, but not in classical or pandemic strains (H5N1, H7N9). HA stem-specific IgG1 antibody titers showed a significant correlation with ADCC/ADCP activity breadth, but no correlation was observed with neutralization breadth. Conclusions: These findings suggest that although current influenza vaccines can induce HA stem-targeted cross-reactive antibodies, their quantity may be insufficient for broad cross-protection, underscoring the need for improved vaccine strategies. Full article

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. Full article

Background: Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed to identify and evaluate the efficacy of a novel influenza universal vaccine candidate consisting of multiple polypeptides derived from highly conserved regions of influenza virus proteins hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). Methods: Immunoinformatics tools were used to screen conserved epitopes from different influenza virus subtypes (H1N1, H3N2, H5N1, H7N9, H9N2, and IBV). A polypeptide vaccine, P125-H, was constructed by linking multiple epitopes using Ii-Key technology. The immunogenicity of P125-H was assessed in mice using MF59-adjuvanted P125-H via intraperitoneal injection. Hemagglutination inhibition (HI) and neutralizing antibody responses were measured, along with IFN-γ levels in spleen lymphocytes. Protective efficacy was evaluated using viral challenge with lethal doses of H1N1 and H7N9. Results: Mice immunized with P125-H generated high levels of HI and neutralizing antibodies against multiple influenza strains. IFN-γ production was significantly elevated in spleen lymphocytes upon stimulation with the vaccine. P125-H protected mice from influenza infection, reducing weight loss and the viral load in the lungs, mitigating lung pathology, and decreasing mortality. Conclusions: The P125-H vaccine induced broad cross-protection against multiple influenza strains and elicited robust immune responses. It demonstrates strong potential as a candidate for a universal influenza vaccine. Full article

Background: Epilepsy is a common neurological disorder in children, associated with significant morbidity and socioeconomic burden. The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, potentially exacerbating seizure control among pediatric epilepsy patients. This study aimed to evaluate the pandemic’s impact on seizure characteristics and identify risk factors contributing to seizure exacerbation in children with epilepsy. Methods: A retrospective cohort study was conducted using medical records of 84 pediatric epilepsy patients at The Catholic University of Korea Yeouido St. Mary’s Hospital from July 2019 to July 2022. Data were collected on demographics, epilepsy characteristics, and healthcare accessibility. Changes in seizure outcomes were analyzed alongside potential risk factors, including infections and socioeconomic variables. Statistical analyses assessed correlations between these factors and seizure exacerbations. Results: Among the 84 pediatric epilepsy patients, 25% experienced significant seizure exacerbations during the COVID-19 pandemic. These included increased seizure frequency (18%), prolonged duration (13%), emergence of new seizure types (4%), and status epilepticus requiring hospitalization (5%). Multivariate analysis identified recent epilepsy diagnosis (<1 year) and low socioeconomic status as independent predictors of seizure worsening (p < 0.05). Infections with non-COVID-19 respiratory viruses, such as RSV and influenza, were strongly associated with exacerbated seizure activity (p < 0.001). Dissatisfaction with access to epilepsy care further increased the risk of poor seizure control, reflecting the challenges posed by disrupted healthcare systems. Notably, no significant relationship was observed between SARS-CoV-2 infection and seizure outcomes, suggesting that indirect factors, rather than direct viral effects, were primary contributors to seizure exacerbation. Conclusions: This study highlights the compounded impact of disrupted healthcare access, socioeconomic challenges, and respiratory viral infections on seizure control during the COVID-19 pandemic. Strategies such as telehealth expansion, regular monitoring, and vaccination against respiratory pathogens are essential to optimize seizure management in future health crises. Full article

Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a self-adjuvant effect enhancing heterologous protection by inducing a robust CD8+ T-cell response together with immunoregulatory mechanisms. However, the effects of NS1 modifications on T-follicular helper (Tfh) and B-cell responses remain less understood. Methods: C57bl/6 mice were immunised intranasally with 10 μL of either an influenza virus containing a truncated NS1 protein (PR8/NS124), a cold-adapted influenza virus with a full-length NS1 (caPR8/NSfull), or a wild-type virus (PR8/NSfull). Immune responses were assessed on days 8 and 28 post-immunisation by flow cytometry, ELISA, and HAI assay. Results: In this study, we demonstrate that intranasal immunisation with PR8/NS124 significantly increases tissue-resident CD4+ and CD8+ T cells in the lungs and activates Tfh cells in regional lymph nodes as early as day 8 post-immunisation. These effects are not observed in mice immunised with caPR8/NSfull or PR8/NSfull. Notably, PR8/NS124 immunisation also leads to the development of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs by day 28, characterised by the presence of antigen-specific Tfh cells and GL7+Fas+ germinal centre B cells. Conclusions: Our findings further underscore the potential of NS1-truncated influenza viruses to drive robust mucosal immune responses and enhance vaccine efficacy. Full article

Recent avian influenza outbreaks have heightened global concern over viral threats with the potential to significantly impact human health. Influenza is particularly alarming due to its history of causing pandemics and zoonotic reservoirs. In response, significant progress has been made toward the development of universal influenza vaccines, largely driven by the discovery of broadly neutralising antibodies (bnAbs), which have the potential to neutralise a broad range of influenza viruses, extending beyond the traditional strain-specific response. This could lead to longer-lasting immunity, reducing the need for seasonal vaccinations, and improve preparedness for future pandemics. This review offers a comprehensive analysis of these antibodies, their application in clinical studies, and both their potential and possible shortcomings in managing future influenza outbreaks. Full article

Background/Objectives: Vaccine hesitancy among immunocompromised patients is complex and not well understood. This study aimed to determine the rate of COVID-19 vaccine hesitancy among pediatric oncology and bone marrow transplant (BMT) patients and to understand associated factors. Methods: Parents of patients (≤18 years) with cancer or post-BMT completed the Parent Attitudes about Childhood Vaccines Survey. A COVID-19 vaccine hesitancy score (VHS-COVID) was calculated from 0 to 100 (higher scores indicating increasing hesitancy). A small group of patients (patients older than 15 years) were also surveyed directly. Results: Among 113 parent respondents, the majority were female (58%) and at least college/university educated (78%). The majority (73%) of patients had cancer (61% leukemia/lymphoma, 37% solid/CNS tumors), while 27% had received BMT for malignant and non-malignant conditions. Only 48% of patients had been vaccinated against COVID-19, compared to 88% of parents. Ineligibility due to phase of cancer/BMT treatment (27%), vaccine hesitancy (24%), and age (24%) were the top three reasons for not vaccinating against COVID-19. Only 13% of parents said they would “definitely vaccinate” if their child became eligible. VHS-COVID scores were higher for parents of patients in surveillance versus active therapy (mean 61 vs. 48; p = 0.03). Parents who had received fewer COVID-19 vaccine doses (0–1 vs. ≥2) were more hesitant toward all vaccines (p = 0.0002), COVID-19 vaccines (p = 0.0003), and influenza vaccines (p = 0.005). Conclusions: Vaccine hesitancy is common among this population and was demonstrated through beliefs (hesitancy scores) as well as vaccine uptake. Future work should focus on education targeting vaccine eligibility and engaging with vaccine hesitant families in the immunocompromised community. Full article