Search Results (195)

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Zoonotic diseases are transmitted from animals to humans, and they impose a significant global burden by impacting both animal and human health. It can lead to substantial economic losses and cause millions of human deaths. The emergence and re-emergence of zoonotic diseases are heavily influenced by both anthropogenic and natural drivers such as climate change, rapid urbanization, and widespread travel. Over time, the unprecedented rise of new and re-emerging zoonotic diseases has prompted the need for rapid and effective vaccine development. Following the success of the COVID-19 mRNA vaccines, mRNA-based platforms hold great promise due to their rapid design, swift development and ability to elicit robust immune responses, thereby highlighting their potential in combating emerging and pre-pandemic zoonotic viruses. In recent years, several mRNA vaccines targeting emerging and re-emerging zoonotic viral diseases, such as rabies, Nipah, Zika, and influenza, have advanced to clinical trials, demonstrating promising immunogenicity. This review explores recent advances, challenges, and future directions in developing mRNA vaccines against emerging and re-emerging zoonotic viral diseases. Full article

Equine Infectious Anemia Virus (EIAV) poses significant diagnostic challenges due to its genetic variability and the limitations of conventional nucleic acid detection methods. This study developed an antigen-capture, enzyme-linked immunosorbent assay (AC-ELISA) for the detection and quantification of the EIAV capsid protein p26. The assay utilized a monoclonal antibody (1G11) specific to the p26 protein as the capture antibody and a polyclonal antibody as the detection antibody, forming a highly specific and sensitive detection system. Under optimized conditions, the detection limit of the AC-ELISA was 1.95 ng/mL, with a good linear relationship observed between 1.95 ng/mL and 60.5 ng/mL of p26 protein. Additionally, the AC-ELISA effectively distinguished EIAV from other equine viruses, including equine herpesvirus 1 (EHV-1), equine arteritis virus (EAV), and equine influenza virus (EIV), without cross-reactivity. Importantly, the AC-ELISA demonstrated the ability to detect multiple EIAV strains, including virulent strains, attenuated strains, and strains from other countries, highlighting its broad applicability across diverse EIAV isolates. Compared to western blot and reverse transcriptase assays, the AC-ELISA exhibited higher sensitivity and strong correlation in quantifying the EIAV p26 protein. The assay is simple, rapid, and cost-effective, making it suitable for both laboratory research and clinical applications. It provides a powerful tool for EIAV detection and quantification, supporting future vaccine development and clinical trials. Full article

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations at patch tests. The present multi-center study investigated the epidemiological, occupational and temporal pattern of sensitization to Thimerosal in North-Eastern Italy during 1997–2023 and associated factors. Methods: Due to variability in patch testing and positive reactions by the centers, this study was broken down by three periods: 1997–2004 (including all centers but Trieste); 1997–2015 (considering only Padua and Pordenone); and 2010–2023 (considering only Trieste and Pordenone). Multiple logistic regression was used to investigate prevalence of sensitization to Thimerosal and associated factors. Results were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (95%CI). Results: Prevalence of positive patch test reactions to Thimerosal decreased from (8.13%) in 1997 to 0.95% in 2023 across all centers combined. Prevalence of positivity to Thimerosal was 9.49% during 1997–2004 (in all centers yet excluding Trieste), 8.41% during 1997–2015 (considering only Padua and Pordenone) and 4.01% during 2010–2023 (considering only Trieste and Pordenone). A significantly decreasing trend of Thimerosal sensitization was observed during 1997–2015 (aOR = 0.94; 95%CI: 0.92; 0.95). Regardless of the study period, sensitization to Thimerosal was consistently and significantly higher among health care workers (HCWs) and in patients born during 1981–1990. Conclusions: The significantly decreasing prevalence of sensitization to Thimerosal over time likely reflected removal policies from vaccines and medications after 1999. Likewise, the higher prevalence of patch test reactions in patients born during 1981–1990 may mirror the widespread presence of this hapten in vaccines and medications in the 1980ies. Moreover, the increased prevalence of patch test reactions positive to Thimerosal in HCWs probably reflected higher influenza vaccination uptake in this group compared to other occupational categories. Positive patch test reactions to Thimerosal after 2000 were likely clinically irrelevant though. Full article

Background/Objectives: Influenza infection is associated with cardiovascular morbidity and mortality; however, the effect of influenza vaccination on cardiovascular outcomes is not fully understood. This clinical trial aimed to investigate the correlation between cardiovascular outcomes and influenza vaccine (FluVac) in coronary artery disease (CAD) subjects. Methods: This was a randomized single-blinded placebo-controlled trial. Enrolled CAD subjects received 0.5 mL of 2007–2008 trivalent FluVac (15 µg hemagglutinin of each of Solomon Islands/3/2006 (H1N1), Wisconsin/67/2005 (H3N2), and Malaysia/2506/2004 (B)). The subjects were followed up at 1 month (hemagglutinin (HA) antibody titers) and at 12 months post-vaccination for evaluation of outcomes (influenza-like episodes, acute coronary syndrome (ACS), myocardial infarction (MI), coronary revascularization, and death). Results: In total, 278 eligible CAD subjects were randomized to receive either FluVac (n = 137) or a placebo (n = 141), of which consequently 131 and 135 subjects completed the study. Cardiovascular deaths (3/131 [2.29%] vs. 3/135 [2.22%]) and all-cause deaths (4/131 [3.05%] vs. 4/135 [2.96%]) were similar in both groups. Adverse cardiovascular events, including ACS, MI, and coronary revascularization, were less frequent in the vaccine group but did not reach statistical significance. The magnitude of the antibody change and serologic response (≥4-fold HI titer rise) of all three antibodies were significantly higher in the vaccine group compared to the placebo but did not correlate with cardiovascular outcomes in the FluVac group. Conclusions: The influenza vaccine may improve cardiovascular outcomes, though this improvement is not correlated with post-vaccination antibody titers. Despite the controversy, influenza vaccination is recommended in the CAD population (clinicaltrials.gov; NCT00607178). Full article

Background/Objectives: Patients with chronic lung diseases, such as cystic fibrosis, were considered a risk group for a severe course of coronavirus disease 2019 at the beginning of the pandemic. However, mounting evidence suggests that this group may not face an elevated risk for a severe SARS-CoV-2 infection. Methods: Here, we present data on the incidence and clinical course of SARS-CoV-2 infections in a single pediatric CF centre in Austria. Clinical variables were analyzed for their potential impact on disease acquisition and severity. A total of 135 young people with CF were assessed from February 2020 until December 2022. Results: Eighty-four patients were infected with SARS-CoV-2, out of which nine patients reported re-infection, resulting in 93 SARS-CoV-2 infections. Most infections, 76/93 (82%), occurred during the period of omicron variant predominance. Higher body mass index and respiratory colonization with Haemophilus influenzae before the beginning of the pandemic were significantly associated with the risk of acquiring SARS-CoV-2 infection. All patients had an uncomplicated COVID-19 course, regardless of the SARS-CoV-2 variant and COVID-19 vaccine status at infection. The most frequent symptoms were rhinitis (53%), fatigue (49%), cephalea (43%), and fever (38%). Neither oxygen therapy nor hospitalization were needed for any of the patients. Lung function parameters (FEV1, FVC, FEF50, LCI), both in the early post-viral as well as late post-viral stages, were not significantly impacted by SARS-CoV-2 infections. No long-term post-COVID-19 effects were reported. Conclusions: Our single-centre experience suggests that the course of SARS-CoV-2 infections in children and adolescents with CF is primarily mild and uncomplicated. 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: This study aims to evaluate the vaccination status of children with rheumatic diseases (RD) compared to healthy controls (HC) and immunization barriers, as studies examining the vaccination status and factors promoting or hindering vaccination among children RD remain limited. Methods: A cross-sectional study was conducted on children with RD (in a rheumatology clinic) and HC (in a fracture clinic) at a tertiary care center in Canada. Demographics, diagnosis, treatments, and vaccine status were obtained from health records and a provincial electronic vaccine database. A patient/caregiver questionnaire was used to capture perceived immunization barriers, concerns, and satisfaction. Descriptive statistical methods were used for analysis. Results: The study involved 144 children with RD and 111 HC. Data from 94 children with RD and 86 HC, all lifelong Alberta residents, were analyzed for objective vaccination status. Most vaccines were received at rates of 80% or higher, except the influenza vaccine, which had the lowest adherence (34% in RD vs. 21% in HC). In 31% of RD children, vaccinations were withheld due to active disease, healthcare provider advice, or caregiver concerns about side effects. In 27% HC, vaccinations were withheld due to side effects. Both groups primarily relied on their family doctor for vaccination information, and 85% or more expressed satisfaction with the information received. Conclusions: Most children with RD and HC received recommended vaccines, but influenza vaccination gaps were identified. Knowledge about vaccine contraindications in RD is well understood, but perceived safety concerns limit vaccination completeness. Healthcare providers, especially family doctors, pediatricians, and rheumatologists, should be providing education resources for vaccines and be proactive in discussing the safety and necessity of vaccinations. Full article

Background/Objectives: Co-administration of BNT162b2 with licensed seasonal influenza vaccines (SIVs) is recommended by health authorities. We provide a comprehensive summary of the data supporting this practice in adults. Methods: This systematic review consolidates available evidence on the prevalence, safety, immunogenicity, efficacy, and effectiveness of co-administering BNT162b2 and SIVs. Searches were conducted for English studies in adults ≥ 18 years of age between January 2021 and August 2024, with no geographic restriction. Study quality was assessed using Cochrane RoB 2.0 and the Newcastle–Ottawa Scale. Results: Twenty studies (15 observational and 5 clinical trials) were included, mainly conducted in seven countries in Europe and North America. Eight observational studies reported prevalence, twelve reported safety/reactogenicity, six reported immunogenicity, and three evaluated efficacy/effectiveness. Reported co-administration of BNT162b2 vaccines with SIVs increased over time. Of persons receiving BNT162b2, the proportion that reported co-administered SIVs increased from 2.7% in 2021 to 34.1% in 2023. Although variability in outcomes was observed, no consistent pattern indicating a negative impact on immunogenicity from same-day co-administration was identified. Effectiveness was not observed to change when BNT162B2 was co-administered with SIVs. The incidence of systemic and local adverse events was comparable between individuals receiving the vaccines separately and those receiving them co-administered. Conclusions: The findings from this review indicate that the co-administration of BNT162B2 with SIVs is both safe and effective. This highlights the value of co-administration, which could enhance vaccine uptake by streamlining immunization protocols and reducing health visits. Full article

Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to target T cell epitopes can be potentially valuable. Considering the difficulties in obtaining clinical samples and the unique advantages of mice in disease-related research, a mouse model that can simulate human immune responses can be a superior alternative to peripheral blood mononuclear cells for epitope screening. Methods: The T cell epitopes of the A/California/07/2009 (H1N1) virus were predicted and utilized to evaluate the cellular immune responses of HLA-A2/DR1 and HLA-A11/DR1 transgenic mice during epitope screening. The selected peptides were used to immunize these two groups of transgenic mice, followed by a viral challenge to assess their protective efficacy. Results: The epitopes that were predicted and screened could stimulate cellular immune responses in HLA-A2/DR1 transgenic mice, HLA-A11/DR1 transgenic mice, and C57BL/6 mice. Moreover, the transgenic mice exhibited stronger ability to produce IFN-γ than that of the wild-type mice. Upon immunization and subjecting to viral challenge, the selected peptides exhibited protective effects against the influenza virus. Conclusions: The HLA-A2/DR1 and HLA-A11/DR1 transgenic mouse models can be used for the direct screening and validation of influenza virus T cell epitopes, which is crucial for designing T cell epitope vaccines against influenza viruses. Further, this method can be applied in epitope screening and vaccine designing before the spread of other emerging and sudden infectious diseases, thereby supporting epidemic control. Full article

Introduction: Invasive bacterial diseases (IBDs) such as meningitis and sepsis are significant public health concerns, particularly in pediatric populations. This study analyzes the incidence, outcomes, and bacterial serotype distribution of pediatric IBDs in the Veneto Region over 17 years. Methods: An observational study was conducted using data (2007–2023) from the surveillance system of the Veneto Region, including microbiologically confirmed cases in individuals < 18 years. Differences by age groups and trends were statistically assessed. Results: A total of 535 pediatric IBD cases were reported, with Streptococcus pneumoniae (54.6%), Neisseria meningitidis (19.6%), and Streptococcus agalactiae (13.5%) being the most common pathogens. Haemophilus influenzae infections were more commonly represented in infants under 1 year (41.5%), whereas S. pneumoniae and N. meningitidis were more frequent in the 1–4-year age group (40.8% and 37.1%, respectively). Sepsis was the most common clinical presentation (57.2%), followed by meningitis (36.3%). Serotype analysis revealed that S. pneumoniae serotype 3 was the most prevalent, while serogroup B dominated N. meningitidis cases. Temporal trends generally showed a decline in cases until 2019, a drop during the COVID-19 pandemic, and a subsequent resurgence in 2022–2023. Conclusions: Our research underscores the value of evidence-based epidemiology through robust surveillance systems in tracking IBD trends and serotype shifts, essential for guiding vaccination strategies and public health interventions. These insights highlight the effectiveness of vaccination programs and the necessity of ongoing monitoring to inform public health policies. Improved data integration and completeness are recommended to enhance surveillance accuracy. Full article

Since 2022, three cases of human infections of novel H3N8 avian influenza viruses (AIVs) have been confirmed in China. Given the potential for significant public health implications, the prompt detection and containment of the virus is particularly important. Comprehensive analyses were conducted of the complete viral gene sequences of five H3 subtype AIVs that were isolated from chickens, pigeons, and geese in live poultry markets in China in 2023. Four strains exhibited a high degree of homology with the H3N8 viruses responsible for human infections in 2022 and 2023. A subsequent study was conducted to investigate the pathogenicity differences among multiple subtypes of the H3 AIVs in chickens. The study revealed that all infected chickens exhibited clinical signs and viral shedding. Notably, two H3N8 viruses, which were highly homologous to human strains, demonstrated significant differences in adaptability to chickens. The goose-derived H3N5 strain displayed high adaptability to chickens and could replicate in multiple organs, with the highest titer in the cloaca. Additionally, a potential vaccine strain, designated CK/NT308/H3N3, was successfully developed that provided complete clinical protection and effectively prevented viral shedding against both H3N3 and H3N8 viruses. In conclusion, CK/NT308/H3N3 presents a promising vaccine candidate. Full article

Background: During the 2023–2024 season, the influenza epidemic in South Korea peaked earlier, and the influenza vaccination rate among individuals aged ≥ 65 was high (82.2%). However, data on real-world vaccine effectiveness against influenza are lacking. Methods: From November 2023 to April 2024, we conducted a multicenter retrospective case–control study on adult patients aged ≥ 18 years who presented with influenza-like illness at seven medical centers as a part of a hospital-based influenza morbidity and mortality surveillance (HIMM) program in South Korea. Demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we assessed the effectiveness of the 2023–2024 seasonal influenza vaccine, with age, sex, and comorbidities included as covariates. Results: A total of 3390 participants were enrolled through the HIMM system, including 1695 patients with either rapid antigen test (RAT) or real-time reverse-transcription polymerase chain reaction (RT-PCR) positive results and controls matched for age, sex, and months of registration. Among the 1696 influenza-positive patients, 1584 (93.5%) underwent RAT, with 88.9% testing positive for influenza A and 11.1% for influenza B. During the study periods, the overall vaccine effectiveness (VE) was 24.3% (95% confidence interval (CI), 11.5 to 35.2). The VE was insignificant when limited to older adults aged ≥ 65 years (13.5%; 95% CI, −17.9 to 36.6). In the subgroup analysis by subtype, the VE was 19.0% (95% CI, 5.0 to 31.0) for influenza A and 56.3% (95% CI, 35.3 to 70.6) for influenza B. Notably, influenza VE was 20.4% (95% CI, 2.9 to 34.8) in the early period (November to December) but decreased to 12.4% (95% CI, −14.9 to 33.2) in the late period (January to April). Conclusion: During the 2023–2024 season, the influenza vaccine showed a modest effectiveness (24.3%) against laboratory-confirmed influenza, which was particularly higher for influenza B. Because the VE was insignificant in older adults, particularly during the late period, better immunogenic influenza vaccines with longer-lasting protection should be considered. Full article

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article