Search Results (85)

The 2025 avian influenza A(H5N1) outbreak has highlighted the urgent need for rapidly generated health communication materials during public health emergencies. Artificial intelligence (AI) systems offer transformative potential to accelerate content development pipelines while maintaining scientific accuracy and impact. We evaluated an AI-generated health communication material on bird flu precautions among 100 U.S. adults. The material was developed using ChatGPT for text generation based on CDC guidelines and Leonardo.AI for illustrations. Participants rated perceived message effectiveness, quality, realism, relevance, attractiveness, and visual informativeness. The AI-generated health communication material received favorable ratings across all dimensions: perceived message effectiveness (3.83/5, 77%), perceived message quality (3.84/5, 77%), realism (3.72/5, 74%), relevance (3.68/5, 74%), attractiveness (3.62/5, 74%), and visual informativeness (3.35/5 67%). Linear regression analysis revealed that all features significantly predicted perceived message effectiveness in unadjusted and adjusted models (p < 0.0001), e.g., multivariate analysis of outcome on perceived visual informativeness showed β = 0.51, 95% CI: 0.37–0.66, p < 0.0001. Also, mediation analysis revealed that visual informativeness accounted for 23.8% of the relationship between material attractiveness and perceived effectiveness. AI tools can enable real-time adaptation of prevention guidance during epidemiological emergencies while maintaining effective risk communication. Full article

The 100-Day Mission, coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI) and endorsed by significant international stakeholders, aims to shorten the timeframe for developing and implementing vaccines to 100 days after the report of a new pathogen. This ambitious goal is outlined as an essential first step in improving pandemic preparedness worldwide. This review highlights the mission’s implementation potential and challenges by examining it through the lens of low- and middle-income countries (LMICs), which often face barriers to equitable vaccine access. This article explores the scientific, economic, political, and social aspects that could influence the mission’s success, relying on lessons learned from previous pandemics, such as the Spanish flu, H1N1, and COVID-19. We also examined important cornerstones like prototype vaccine libraries, accelerated clinical trial preparedness, early biomarkers identification, scalable manufacturing capabilities, and rapid pathogen characterization. The review also explores the World Health Organization (WHO) Pandemic Agreement and the significance of Phase 4 surveillance in ensuring vaccine safety. We additionally evaluate societal issues that disproportionately impact LMICs, like vaccine reluctance, health literacy gaps, and digital access limitations. Without intentional attempts to incorporate under-resourced regions into global preparedness frameworks, we argue that the 100-Day Mission carries the risk of exacerbating already-existing disparities. Ultimately, our analysis emphasizes that success will not only rely on a scientific innovation but also on sustained international collaboration, transparent governance, and equitable funding that prioritizes inclusion from the beginning. Full article

Since 2020, the Gs/Gd H5N1 influenza virus (clade 2.3.4.4b) has established itself within wild bird populations across Asia, Europe, and the Americas, causing outbreaks in wild mammals, commercial poultry, and dairy farms. The impacts on the bird populations and the agricultural industry has been significant, requiring a One Health approach to enhanced surveillance in both humans and animals. To support pandemic preparedness efforts, we evaluated the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel for their ability to detect the presence of non-seasonal, zoonotic influenza A viruses, including circulating H5N1 viruses from clade 2.3.4.4b. Both assays effectively detected the presence of influenza virus in clinically-contrived nasal swab and saliva specimens at low concentrations. The results generated using the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel, in conjunction with clinical and epidemiological findings provide valuable diagnostic findings that can strengthen pandemic preparedness and surveillance initiatives. Full article

Background/Objectives: The co-circulation of both influenza viruses and SARS-CoV-2 poses a significant health risk, especially for the elderly. While vaccination against both diseases remains an effective strategy to reduce the burden of symptomatic infections, the effect of administering COVID-19 mRNA and seasonal influenza vaccines (COV-Flu) on elicited antibody responses has not been explored. Methods: Participants between 18 and 90 years old were vaccinated with COVID-19 mRNA vaccines (n = 67), seasonal influenza vaccines (n = 130), or both (n = 201) within a three-month period between 2021 and 2024. Serum hemagglutination-inhibition (HAI) titers against influenza A (H1N1, H3N2) and B (Yamagata, Victoria) strains were measured from the COV-Flu participants or the participants vaccinated with influenza vaccines only (mono-Flu). SARS-CoV-2 neutralization assays were performed on sera collected from the COV-Flu participants and the participants receiving the mRNA vaccine only (mono-COVID-19). Results: The administration of influenza virus vaccines and COVID-19 mRNA vaccines within a three-month period significantly enhanced the post-vaccination HAI titers against both influenza A and B vaccine components, particularly in the elderly (65–90) participants. There were no significant differences in SARS-CoV-2 neutralization titers in COV-Flu participants compared to mono-COVID-19 participants. Conclusions: Vaccination with both the COVID-19 mRNA and influenza vaccines enhances influenza-specific HAI titers without compromising the neutralization titers elicited by COVID-19 mRNA vaccination against SARS-CoV-2, especially in the elderly. These findings indicate the potential benefits of this approach, particularly for older adults, by boosting influenza virus vaccine-induced serum HAI activity while maintaining COVID-19 protective immunity. Full article

Influenza A viruses (IAVs) evolve rapidly, exhibit zoonotic potential, and frequently adapt to new hosts, often establishing long-term reservoirs. Despite advancements in genetic sequencing and phylogenetic classification, current influenza nomenclature systems remain static, failing to capture evolving epidemiological patterns. This rigidity has led to delays or misinterpretations in public health responses, economic disruptions, and confusion in scientific communication. The existing nomenclature does not adequately reflect real-time transmission dynamics or host adaptations, limiting its usefulness for public health management. The 2009 H1N1 pandemic exemplified these limitations, as it was mischaracterized as “swine flu” despite sustained human-to-human transmission and no direct pig-to-human transmission reported. This review proposes a real-time, transmission-informed nomenclature system that prioritizes host adaptation and sustained transmissibility (R₀ > 1) to align influenza classification with epidemiological realities and risk management. Through case studies of H1N1pdm09, H5N1, and H7N9, alongside a historical overview of influenza naming, we demonstrate the advantages of integrating transmission dynamics into naming conventions. Adopting a real-time, transmission-informed approach will improve pandemic preparedness, strengthen global surveillance, and enhance influenza classification for scientists, policymakers, and public health agencies. 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: Humoral immunity directed against neuraminidase (NA) of the influenza virus may soften the severity of infection caused by new antigenic variants of the influenza viruses. Evaluation of NA-inhibiting (NI) antibodies in combination with antibodies to hemagglutinin (HA) may enhance research on the antibody response to influenza vaccines. Methods: The study examined 64 pairs of serum samples from patients vaccinated with seasonal inactivated trivalent influenza vaccines (IIVs) in 2018 according to the formula recommended by the World Health Organization (WHO) for the 2018–2019 flu season. Antibodies against drift influenza viruses A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09 and A/Brisbane/34/2018(H3N2) were studied before vaccination and 21 days after vaccination. To assess NI antibodies, we used an enzyme-linked lectin assay (ELLA) with pairs of reassortant viruses A/H6N1 and A/H6N2. Anti-HA antibodies were detected using a hemagglutination inhibition (HI) test. The microneutralization (MN) test was performed in the MDCK cell line using viruses A/H6N1 and A/H6N2. Results: Seasonal IIVs induce a significant immune response of NI antibodies against influenza A/H1N1pdm09 and A/H3N2 viruses. A significantly reduced ‘herd’ immunity to drift influenza A/H1N1pdm09 and A/H3N2 viruses was shown, compared with previously circulating strains. This reduction was most pronounced in strains possessing neuraminidase N2. Seasonal IIVs caused an increase in antibodies against homologous and drifted viruses; however, an increase in antibodies to drifting viruses was observed more often among older patients. The level of NI antibodies for later A/H1N1pdm09 virus in response to IIVs was statistically significantly lower among younger people. After IIV vaccination, the percentage of individuals with HI antibody levels ≥ 1:40 and NI antibody levels ≥ 1:20 was 32.8% for drift A/H1N1pdm09 virus and 17.2% for drift A/H3N2 virus. Antisera containing HI and NI antibodies exhibited neutralizing properties in vitro against viruses with unrelated HA of the H6 subtype. Conclusions: Drift A/H1N1pdm09 and A/H3N2 viruses demonstrated significantly lower reactivity to HI and NI antibodies against early influenza viruses. In response to seasonal IIVs, the level of seroprotection has increased, including against drift influenza A viruses, but protective antibody levels against A/H1N1pdm09 have risen to a greater extent. A reduced immune response to the N1 protein of the A/H1N1pdm09 drift virus was obtained in individuals under 60 years of age. Based on our findings, it is hypothesized that in the cases of a HA mismatch, vaccination against N1-containing influenza viruses may be necessary for individuals under 60, while broader population-level vaccination against N2-containing viruses may be required. Full article

‘Frozen’ virus genome sequences are sampled from outbreaks and have unusually low sequence divergence when compared to genome sequences from historical strains. A growing number of ‘frozen’ virus genome sequences are being reported as virus genome sequencing becomes more common. Examples of ‘frozen’ sequences include the 1977 H1N1 ‘Russian’ flu; Venezuelan Equine Encephalitis Virus from Venezuela and Colombia in 1995; E71 sequences from a Hand, Foot and Mouth outbreak in 2007–2009 in China; and a polio strain isolated in 2014 from Anhui, China. The origin of these ‘frozen’ sequences has been attributed to escapes from research facilities and often appears to be associated with vaccine work. Consequently, a new paradigm for pathogen emergence appears in operation, that involves laboratory research or vaccine production which utilizes ‘live’ virus isolates of historical strains. The accidental release and re-emergence of such strains are straightforward to detect from their genome sequences and should spur the routine sequencing and publication of all known pathogenic viral strains undergoing experimentation, or being used for vaccine manufacture, in order to facilitate tracing. However, it is noted that novel pathogenic viruses accidentally released into the population from research facilities are harder to detect if their sequence has first not been made public, which should prompt the routine sequencing and reporting of all novel pathogenic viruses before experimentation. Full article

Pediatric patients who have undergone hematopoietic stem cell transplantation (HSCT) or chemotherapy are at increased risk for severe influenza complications, necessitating annual vaccination. This study evaluated the immunogenicity and antibody persistence of the 2021–2022 seasonal quadrivalent influenza vaccine in pediatric patients post-HSCT or chemotherapy, compared to healthy controls. A prospective cohort study included 80 pediatric participants divided into three groups: chemotherapy (n = 33), HSCT (n = 27), and healthy controls (n = 20). All participants were vaccinated with the 2021–2022 GC FLU Quadrivalent vaccine. Hemagglutination inhibition (HI) assays measured seroprotection rates (SPR), geometric mean titers (GMT), and seroconversion rates (SCR) for the four vaccine antigens (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) at one, three, and six months post-vaccination. At one month post-vaccination, all groups met the 70% SPR threshold for A/H1N1 and A/H3N2, but not for B/Victoria. For B/Yamagata, the SPR was low in the chemotherapy and HSCT groups (18.18% and 33.33%, respectively), compared to 80.00% in controls (p < 0.0001 and p = 0.0015). While A/H1N1 and A/H3N2 GMTs were protective in all groups, only controls achieved protective levels for B/Yamagata. Over time, the control group maintained >70% SPR for A/H1N1 up to six months, but the chemotherapy and HSCT groups declined by three and six months, respectively. For A/H3N2, the SPR in controls dropped below 70% at three months, while it remained above 70% in the chemotherapy and HSCT groups until three months. None of the groups achieved protective GMTs for B strains at three or six months. Pediatric patients post-HSCT or chemotherapy demonstrated a comparable immune response to healthy controls for A/H1N1 and A/H3N2, but the rapid decline in A/H1N1 antibody levels suggests the need for ongoing monitoring and adjusted vaccination schedules. The poor response to B antigens, particularly B/Yamagata, underscores the need for improved vaccination strategies in these vulnerable populations. Full article

Influenza A virus (IAV) is known for causing seasonal epidemics ranging from flu to more severe outcomes like pneumonia, cytokine storms, and acute respiratory distress syndrome. The innate immune response and inflammasome activation play pivotal roles in sensing, preventing, and clearing the infection, as well as in the potential exacerbation of disease progression. This study examines the complex relationships between donor-specific characteristics and cytokine responses during H3N2 IAV infection using an ex vivo model. At 24 h post infection in 31 human lung explant tissue samples, key cytokines such as interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) were upregulated. Interestingly, a history of lung cancer did not impact the acute immune response. However, cigarette smoking and programmed death-ligand 1 (PD-L1) expression on macrophages significantly increased IL-2 levels. Conversely, age inversely affected IL-4 levels, and diabetes mellitus negatively influenced IL-6 levels. Additionally, both diabetes mellitus and programmed cell death protein 1 (PD-1) expression on CD3⁺/CD4⁺ T cells negatively impacted TNF-α levels, while body mass index was inversely associated with IFN-γ production. Toll-like receptor 2 (TLR2) expression emerged as crucial in mediating acute innate and adaptive immune responses. These findings highlight the intricate interplay between individual physiological traits and immune responses during influenza infection, underscoring the importance of tailored and personalized approaches in IAV treatment and prevention. Full article

Seasonal influenza viruses continuously evolve via antigenic drift. This leads to recurring epidemics, globally significant mortality rates, and the need for annually updated vaccines. Co-occurring mutations in hemagglutinin (HA) and neuraminidase (NA) are suggested to have synergistic interactions where mutations can increase the chances of immune escape and viral fitness. Association rule mining was used to identify temporal relationships of co-occurring HA–NA mutations of influenza virus A/H3N2 and its role in antigenic evolution. A total of 64 clusters were found. These included well-known mutations responsible for antigenic drift, as well as previously undiscovered groups. A majority (41/64) were associated with known antigenic sites, and 38/64 involved mutations across both HA and NA. The emergence and disappearance of N-glycosylation sites in the pattern of N-X-[S/T] were also identified, which are crucial post-translational processes to maintain protein stability and functional balance (e.g., emergence of NA:339ASP and disappearance of HA:187ASP). Our study offers an alternative approach to the existing mutual-information and phylogenetic methods used to identify co-occurring mutations, enabling faster processing of large amounts of data. Our approach can facilitate the prediction of critical mutations given their occurrence in a previous season, facilitating vaccine development for the next flu season and leading to better preparation for future pandemics. Full article

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates’ ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay’s effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel^® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay’s potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations. Full article

Objectives: This study aimed to determine the safety, tolerability and immunogenicity of TetraFluBet, an inactivated subunit influenza vaccine that contains a corpuscular immuno-adjuvant derived from natural betulin. Methods: We conducted a prospective, randomized, open-labeled, single-center, phase I trial. The study was conducted in two stages: 5 volunteers in stage I and 25 volunteers in stage II. Eligible participants received one single dose (20 μg/0.5 mL) of TetraFluBet intramuscularly. Participants were followed for adverse events and reactogenicity. Seroconversion rate, seroprotection level, geometric mean titers (GMTs) of virus-neutralizing antibodies, IFN-γ induction and cell-mediated immunity were assessed. Results: A total of 30 participants were enrolled. No vaccine-related serious adverse events were observed. The proportions of study participants with 4-fold seroconversions assessed by the HI assay (with 95% CIs) were 80.0% (62.7; 90.5), 70.0% (52.1; 83.3), 63.3% (45.5; 78.1) and 73.3% (55.6; 85.8) for influenza virus subtypes A (H1N1), A (H3N2), B1 and B2, respectively. Seroprotection levels (with 95% CIs) were 83.3% (66.4; 92.7), 83.3% (66.4; 92.7), 73.3% (55.6; 85.8) and 66.7% (48.8; 80.8), respectively. The fold increases in the GMTs of virus-neutralizing antibodies for subtype H1N1 was 6.50, for subtype H3N2 was 3.03, for subtype B1 was 3.56 and for subtype B2 was 6.07. The population of cytotoxic T-cells increased significantly in the post-vaccination period, indicating a strong CD3⁺CD8⁺ response. Conclusions: TetraFluBet tetravalent inactivated subunit vaccine with adjuvant demonstrated pronounced immunogenic properties, leading to the formation of both specific humoral and cellular immunity at a 20 μg dose. Full article

The current study explored the differential interaction between ethylene (ET) and abscisic acid (ABA) in relation to salt stress in mustard (Brassica juncea L.) plants. Significant reductions in seed germination, growth, and photosynthesis were observed with 100 mmol NaCl. Among the cultivars tested, the Pusa Vijay cultivar was noted as ET-sensitive. Pusa Vijay responded maximally to an application of 2.0 mmol ethephon (Eth; 2-chloethyl phosphonic acid-ethylene source), and exhibited the greatest growth, photosynthesis, activity of 1-aminocyclopropane carboxylic acid (ACC) synthase (ACS), and ET evolution. Notably, Eth (2.0 mmol) more significantly improved the seed germination percentage, germination and vigor index, amylase activity, and reduced H₂O₂ content under salt stress, while ABA (25 µmol) had negative effects. Moreover, the individual application of Eth and ABA on Pusa Vijay under both optimal and salt-stressed conditions increased the growth and photosynthetic attributes, nitrogen (N) and sulfur (S) assimilation, and antioxidant defense machinery. The addition of aminoethoxyvinylglycine (0.01 µmol AVG, ET biosynthesis inhibitor) to ABA + NaCl-treated plants further added to the effects of ABA on parameters related to seed germination and resulted in less effectiveness of growth and photosynthesis. In contrast, the effects of Eth were seen with the addition of fluoridone (25 µmol Flu, ABA biosynthesis inhibitor) to Eth + NaCl. Thus, it can be suggested that ET is crucial for alleviating salt-induced inhibition in seed germination, growth, and photosynthesis, while ABA collaborated with ET to offer protection by regulating nutrient assimilation and enhancing antioxidant metabolism. These findings provide insight into the complex regulatory processes involved in ET–ABA interaction, enhancing our understanding of plant growth and development and the mitigation of salt stress in mustard. It opens pathways for developing hormonal-based strategies to improve crop productivity and resilience, ultimately benefiting agricultural practices amidst a challenging environment. Full article

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body’s immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-β, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT’s antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections. Full article