Search Results (251)

Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (Mhp) are major contributors to the porcine respiratory disease complex. Although PCV2-Mhp bivalent inactivated vaccines are useful for simultaneous disease control, their immunogenicity may be improved by adjuvant optimization. This study evaluated a composite adjuvant consisting of porcine interleukin-2 (IL-2), IL-4, IL-6 and MnJ(beta), a colloidal manganese adjuvant, in an initial murine immunogenicity model. Thirty female Kunming mice were assigned to three groups (n = 10/group): bivalent antigen plus IL-2/IL-4/IL-6/MnJ(beta), bivalent antigen plus MnJ(beta), or phosphate-buffered saline. Body weight, complete blood count, peripheral blood T- and B-cell subsets, PCV2-specific IgG and Mhp-specific indirect hemagglutination titers were monitored after primary and booster immunization. The composite formulation did not suppress body-weight gain or induce sustained abnormalities in erythrocyte- or platelet-related indices. WBC, neutrophil, lymphocyte and monocyte counts were elevated in group A at days 7 and 28 post-primary immunization, indicating transient immune activation. Day-56 flow cytometry indicated increased CD19+IgM-IgD- B-cell and effector/memory T-cell-associated responses. PCV2-specific IgG increased from day 14 onward. At day 56, the OD450 value in group A reached 1.532 ± 0.006, compared with 1.095 ± 0.004 in group C1 and 0.102 ± 0.002 in group C2, corresponding to approximately 1.40-fold and 15.09-fold higher levels than the MnJ(beta)-adjuvanted and PBS control groups, respectively. Mhp-specific IHA titers were also maintained at high levels after booster immunization; at day 56, group A showed a log2 endpoint titer of 13.00 ± 0.00, corresponding to a GMT of 1:8192, whereas group C1 showed a log2 endpoint titer of 12.00 ± 0.00, corresponding to a GMT of 1:4096, and group C2 remained negative. These results indicate that the IL-2/IL-4/IL-6/MnJ(beta) composite adjuvant demonstrates potential for improving antibody and peripheral lymphocyte responses to PCV2-Mhp bivalent antigen, but protective efficacy must be confirmed in target-species challenge studies. Full article

Background/Objectives: Pandemic influenza remains a persistent global threat, and while vaccination is the primary preventive measure, conventional vaccines often induce narrow, strain-specific immunity. This study evaluated the immunogenicity, protective efficacy, and cross-protective potential of a CpG-adjuvanted trivalent inactivated influenza vaccine (CpG-TIV) administered intramuscularly at high and low doses in ferrets. Methods: Groups of influenza-seronegative ferrets received two intramuscular injections, 3 weeks apart, of high- or low-dose CpG-TIV or a commercial non-adjuvanted trivalent vaccine. Three weeks after the second immunization (Day 42), serum was obtained, and the ferrets were subsequently challenged intranasally with homologous H1N1 and influenza B viruses, as well as a heterologous drifted H3N2 strain. Clinical signs, body weight, nasal viral load, and lung histopathology were monitored following the viral challenge. Results: CpG-TIV induced significantly higher dose-dependent HI and IgG antibodies than the commercial unadjuvanted vaccine. High-dose CpG-TIV markedly reduced weight loss, clinical symptoms, nasal viral load (by up to 99%), and lung pathological damage. Notably, high-dose CpG-TIV provided significant cross-protection against heterologous H3N2, whereas the commercial vaccine showed no protective effect. At Day 42, HI GMTs in the high-dose group reached 500, 254, and 594 against H1N1, H3N2, and B strains, respectively, with a maximal 2.58 log10 reduction in H1N1 viral load. Conclusions: High-dose CpG-TIV demonstrates strong immunogenicity and robust dose-dependent homologous and heterologous cross-protection in ferrets. The combination of a CpG adjuvant and high-dose antigen broadens protection against drifted influenza viruses, overcoming the narrow coverage of conventional vaccines. These data support further clinical development of this broad-spectrum influenza vaccine candidate. Full article

The Target–Attacker–Defender (TAD) pursuit–evasion game is a core challenge in multi-agent cooperative control, yet real-world settings involving dynamic team scaling and strict energy constraints remain largely unaddressed. When scalable shared-parameter policies are adopted to cope with the varying number of agents, severe policy homogeneity emerges, preventing effective division of labor. This paper proposes a Hierarchical Heterogeneous Multi-Agent Proximal Policy Optimization (HH-MAPPO) framework to resolve these challenges. Both levels employ actor–critic networks with Role-Aware Embedding (RAE). In this mechanism, each agent is assigned a unique, learnable role embedding derived from its identity. These embeddings serve as conditioning inputs to the shared policy network, enabling it to generate differentiated behaviors and effectively mitigating policy homogeneity. The upper-level policy determines the number of defenders to deploy and assigns interception targets, while the lower-level policy handles continuous control of each defender and the ground moving target (GMT). This hierarchy resolves dynamic observation spaces via a target-matching mechanism, where each defender’s observation includes only its own state and its assigned attacker’s state, keeping observation dimension constant. Experiments in a 3D TAD simulation with continuous attacker arrivals and energy-constrained defenders show the following: (1) HH-MAPPO achieves superior interception performance compared to baseline methods in both symmetric and asymmetric scenarios; (2) ablation studies confirm RAE increases policy diversity, raising Sequence-Based Action Dissimilarity (SBAD) by 15.5%; and (3) Pareto analysis demonstrates a superior performance–energy trade-off, maintaining about 70% interception rate even under an extreme energy cap (E = 30). Full article

Background: The BNT162b2 vaccine is safe and effective for COVID-19 prevention. BNT162b2 safety and immunogenicity have been evaluated in immunocompromised individuals in real-world observational studies, particularly in pediatric populations, but not in clinical trials. Methods: This phase 2b single-arm trial descriptively evaluated a Dose 3 (age-appropriate) BNT162b2 primary series with a Dose 4 in immunocompromised individuals 2–<5, 5−<12, 12–<18, and ≥18 years of age without a previous clinical or microbiological COVID-19 diagnosis. Primary objectives were to describe immune responses, reactogenicity, and adverse events following vaccination. Results: Out of 124 participants enrolled, 119 received Dose 3 and 90 received Dose 4. Among participants without evidence of past SARS-CoV-2 infection, neutralizing geometric mean titers (GMTs) and geometric mean fold rises (GMFRs) against the SARS-CoV-2 ancestral strain ranged from 344.6 to 1584.4 and 7.9 to 36.4 at 1 month after Dose 3 and from 1474.0 to 4157.9 and 31.0 to 95.6 at 1 month after Dose 4, respectively, across age groups. Among participants with or without evidence of past infection, GMTs and GMFRs ranged from 787.1 to 2940.6 and 9.6 to 54.3 at 1 month after Dose 3 and from 1031.3 to 13,457.1 and 9.1 to 220.0 at 1 month after Dose 4. Percentages of participants with or without evidence of past SARS-CoV-2 infection achieving seroresponse ranged from 50.0 to 92.9% at 1 month after Dose 3, and from 75.0 to 100% and 33.3 to 100.0% at 1 and 6 months after Dose 4 across age groups, respectively. No new safety signals were identified. Conclusions: BNT162b2 was immunogenic, increasing GMTs in immunocompromised individuals ≥2 years old, particularly after Doses 3 and 4. GMT increases were generally similar across age groups and disease subsets. Three or four BNT162b2 doses had a favorable risk-benefit profile in this population. Full article

Background/Objectives: Human papillomavirus (HPV) infection is the leading cause of cervical cancer and is associated with several anogenital and oropharyngeal malignancies. Although licensed HPV vaccines are highly effective, access remains limited in many low- and middle-income countries due to cost, supply shortages, and implementation barriers. In this study, we evaluated the immunogenicity and safety of Gardisun, a newly developed quadrivalent prophylactic HPV vaccine, compared with Gardasil^®. Methods: This Phase III randomized, double-blind, active-controlled, parallel-group non-inferiority trial enrolled 450 healthy participants stratified by sex and randomized (1:1) to receive three 0.5 mL intramuscular doses of Gardisun or Gardasil^® on Days 0, 60, and 180. Participants were followed through to Day 210. The primary endpoint was the geometric mean titer (GMT) of antibodies against HPV types 6, 11, 16, and 18 one month after the administration of the third dose. Non-inferiority was defined as the lower bound of the 95% confidence interval (CI) for the GMT ratio exceeding 0.67. Safety was assessed through adverse event monitoring. Results: Of the 450 randomized participants, 422 completed the Month 7 visit and 429 received all three doses. Both vaccines induced antibody responses and seroconversion rates for all HPV types. The primary analysis met the non-inferiority criterion for HPV-6, while prespecified sensitivity analyses supported the existence of non-inferiority across all evaluated HPV types. Most adverse events were mild and transient, with no vaccine-related serious adverse events reported. Conclusions: Gardisun demonstrated robust immunogenicity and a safety profile comparable to that of Gardasil^®, supporting its potential as an accessible alternative quadrivalent HPV vaccine for broader vaccination programs in resource-limited settings. Full article

Background: Hypertrophic olivary degeneration (HOD) is a rare neurological condition resulting from trans-synaptic degeneration of the inferior olivary nucleus (ION) following disruption of the dentato-rubro-olivary pathway, also known as the Guillain–Mollaret triangle (GMT). Although the clinical and radiologic features of HOD have been previously described, the precise temporal correlation between clinical symptom onset and manifestations on magnetic resonance imaging (MRI) remains difficult to establish, and the factors contributing to accelerated disease progression are poorly understood. Case Presentation: A 43-year-old male presented with intracerebral hemorrhage involving the left midbrain, bilateral pons, and cerebellum. Serial MRI was prospectively performed starting four weeks post-hemorrhage, at which time no signal abnormalities were detected in the ION. However, at 9 weeks, T2 hyperintensity first emerged in the bilateral ION. Approximately 2 weeks after this finding, the patient developed characteristic palatal and lingual tremors, accompanied by a dissociated vertical pendular nystagmus that was predominantly monocular (right eye). In addition, severe dysphagia was also noted, with videofluoroscopic swallowing study (VFSS) showing aspiration across all diets. A subsequent MRI obtained at 13 weeks post-insult (two weeks after tremor onset) revealed newly developed bilateral ION hypertrophy, with the maximal diameter increasing from a 5 mm baseline to 7 mm. Follow-up MRI at 17 weeks post-hemorrhage revealed further progression with increased hypertrophy and signal intensity. Dysphagia persisted throughout the clinical course, ultimately necessitating percutaneous endoscopic gastrostomy (PEG) tube insertion. Conclusions: This case provides rare, longitudinal documentation of the clinico-radiologic progression of HOD, facilitated by a pre-insult baseline MRI and prospective serial imaging. Our findings provide a detailed timeline of the transition from signal abnormality to hypertrophy in correlation with clinical symptom emergence. Full article

Background/Objectives: HXP-GPOVac is a locally produced, inactivated Newcastle disease virus-based (NDV-HXP-S) COVID-19 vaccine manufactured in Thailand. This phase II trial compared its safety and immunogenicity with the mRNA vaccine BNT162b2 in adults aged 18–75 years. Methods: In this randomized, double-blind, active-controlled trial registered with the Thai Clinical Trials Registry (TCTR20220819003), 300 participants were assigned 3:1 to receive HXP-GPOVac or BNT162b2 on Days 1 and 29. Solicited adverse events (AEs) were recorded for 7 days after each dose, AEs were summarized through 28 days after each dose, and serious adverse events (SAEs), medically attended AEs (MAAEs), and adverse events of special interest (AESIs) were collected through Day 197. Humoral immunogenicity was assessed by pseudovirus 50% neutralization titers (NT₅₀) and anti-spike IgG concentrations at baseline, Day 29, Day 43, and Day 197. Seroconversion was defined as a ≥4-fold increase from baseline. A predefined subset underwent interferon-γ (IFN-γ) and interleukin-5 (IL-5) ELISpot assays to assess cell-mediated immune responses. The primary immunogenicity analysis assessed non-inferiority of HXP-GPOVac compared with BNT162b2 based on the NT₅₀ geometric mean titer ratio, with a prespecified non-inferiority margin of 0.5. Results: Solicited AEs were predominantly mild and occurred more frequently after the first dose in both groups; one or more solicited local or systemic AEs were reported by 23.7% (95% CI: 18.3–29.8) of HXP-GPOVac recipients and 44.7% (95% CI: 33.3–56.6) of BNT162b2 recipients after the first dose. AEs through 28 days after vaccination and SAEs were uncommon; MAAEs occurred in 17.0% of HXP-GPOVac recipients and 22.4% of BNT162b2 recipients, and none were considered related to vaccination. In the HXP-GPOVac group, NT₅₀ geometric mean titers increased from 5.6 at baseline to 65.5 at Day 29 and 505 at Day 43, declining to 63.6 at Day 197. Anti-spike IgG geometric mean concentrations rose from 7.5 BAU/mL at baseline to 102.7 BAU/mL at Day 29 and 514.6 BAU/mL at Day 43, decreasing to 61.0 BAU/mL at Day 197. BNT162b2 induced higher antibody levels at all time points. The NT₅₀ GMT ratio (HXP-GPOVac/BNT162b2) at Day 43 was 0.51 (95% CI: 0.39–0.67); the lower bound did not exceed the prespecified non-inferiority margin of 0.5, and non-inferiority was not established. Seroconversion rates at Day 43 were 97.6% for HXP-GPOVac and 97.1% for BNT162b2 (neutralizing antibody) and 98.6% and 97.1%, respectively (anti-spike IgG). ELISpot analyses demonstrated increased IFN-γ responses after the second dose without evidence of Th2-dominant skewing. Conclusions: HXP-GPOVac was well tolerated and induced substantial humoral and cellular immune responses, with high seroconversion rates and balanced T-cell polarization. Although absolute antibody levels were lower than those induced by BNT162b2 and the prespecified non-inferiority criterion was not met, these findings support continued evaluation of the inactivated NDV-HXP-S vaccine platform. Full article

Highly pathogenic avian influenza A (H7N9) remains a threat to poultry health and poses a zoonotic risk, highlighting the need for vaccine antigens capable of inducing both systemic and mucosal immunity. In this study, we evaluated X33CLS-H7, a clarified cell-lysate supernatant derived from glycoengineered Pichia pastoris expressing H7 hemagglutinin, in BALB/c mice following intramuscular(i.m.) injection, nebulized inhalation, or intranasal instillation. H7 expression and hemagglutination activity were confirmed by Western blotting and hemagglutination assay, respectively. Serum HA7-specific IgG and IgA responses, hemagglutination inhibition(HI) activity, H7N9 pseudovirus neutralization, bronchoalveolar lavage fluid (BALF) antibodies, and safety readouts were assessed. After two i.m. immunizations, X33CLS-H7 induced the strongest systemic antibody responses, with an HI geometric mean titer of 1:1622 95% CI, 1:1108–1:2348 and a mean log10 NT₅₀ of 4.62. Respiratory immunization also elicited antibody responses. After four doses, high-dose nebulized delivery produced the strongest responses among the respiratory delivery regimens, with serum IgG and IgA titers of 1.02 × 10⁵ and 2.24 × 10³, respectively, an endpoint HI GMT r of 1:457 95% CI, 1:211–1:971, and a mean log10 NT₅₀ of 3.77 compared with 2.02 in saline controls. High-dose nebulized delivery also generated detectable HA7-specific IgG and IgA responses in bronchoalveolar lavage fluid. No overt local or systemic toxicity signals were observed under the tested conditions. These findings indicate that X33CLS-H7 retains HA7-associated antigenicity and can induce systemic and respiratory mucosal antibody responses, supporting its further evaluation as a simplified and scalable H7N9 vaccine antigen candidate. Full article

Background: Antigenic drift limits the protective efficacy of influenza vaccine. Glycosylation of hemagglutinin (HA) represents a promising immunofocusing strategy that enhances neutralizing antibody responses by masking immunodominant non-neutralizing epitopes. Methods: B-cell epitopes of influenza viruses were retrieved from the Immune Epitope Database and were mapped onto the HA structure of A/Puerto Rico/8/1934 (H1N1). Structure-guided analysis identified residues 136 and 137 as candidate sites for N-linked glycosylation (NLG). Single-site mutants (136NLG and 137NLG) were generated using reverse genetics and evaluated for stability, receptor binding, viral replication, and immunogenicity in a murine model with inactivated whole-virus vaccines. Results: Both mutants exhibited increased thermostability at 42 °C. Glycosylation reduced the HA–sialic acid affinity, resulting in decreased viral adsorption and internalization efficiency in MDCK cells, and delayed viral replication at low multiplicity of infection (MOI). In vivo, all vaccine groups provided complete protection against lethal challenge; notably, the 136NLG group exhibited reduced weight loss, indicating improved protective efficacy compared with wild-type (WT). Conclusions: Targeted glycosylation at residue 136 in the HA head domain effectively enhances the viral stability and elicits a 1.78-fold increase in hemagglutination inhibition titer (GMT) relative to the WT, thereby improving vaccine performance. These findings establish a rational and structure-based design strategy for developing more stable and effective influenza vaccines. Full article

This study evaluates structure-preserving neural network architectures for learning holonomically constrained mechanical dynamics in Cartesian coordinates. In contrast to methods using reduced coordinates, the full ambient phase space ${\mathbb{R}}^{2n}$ is retained with explicit algebraic constraints $C_i\left(\mathbf{q}\right)=0$ to provide a test bed for constraint-aware learning. The Constraint-Aware Hamiltonian Neural Network (CA-HNN) is proposed, which augments the standard HNN with a dedicated multiplier network ${\lambda }_{\varphi }(\mathbf{q},\mathbf{p})$ for Lagrange multipliers and a composite loss function evaluated on predicted rollouts. The theoretical framework is grounded in the geometry of constrained Hamiltonian systems: the extended phase space ${\mathbb{R}}^{2n+m}$ carries a degenerate antisymmetric structure where an m-dimensional kernel encodes constraint directions, while the symplectic structure emerges on the $2(n-m)$-dimensional reduced manifold $\Sigma$. It is proven that the physical Hamiltonian is conserved on the constraint surface under augmented flow. Benchmarks on a pendulum ($C=x^2+y^2-l^2$), double pendulum, and bead on a parabola ($C=y-x^2$) demonstrate that CA-HNN reduces constraint violations $\parallel C\left(\mathbf{q}\right)\parallel$ by $5\times$ to $2400\times$ compared to standard HNNs. While the best energy conservation is achieved by PINNs, these findings clarify the roles of architectural inductive bias, constraint augmentation, and soft physics regularization. Full article

Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-γ release assay (IGRA). Data were analyzed using univariate (Fisher’s exact test) and Firth’s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U/mL vs. 258.79 U/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies. Full article

Background/Objectives: Meningococcal disease is primarily caused by serogroups A, B, C, W, and Y. Current US vaccination recommendations include routine serogroup A/C/W/Y (MenACWY) vaccination (ages 11–12 and 16 years) and a two-dose, 0-, 6-month MenB vaccination series (age 16–23 years) based on shared clinical decision-making. Administration of the first-in-class Pfizer pentavalent MenABCWY vaccine (Penbraya^TM), which received US licensure in 2023 as a two-dose, 0-, 6-month series, is endorsed when the MenACWY and MenB vaccines are recommended at the same visit. This study evaluated the immunogenicity and safety of two extended two-dose schedules of MenABCWY in healthy adolescents. Methods: In this observer-blinded, phase 2b study (ClinicalTrials.gov, NCT04440176; 19 June 2020), 309 healthy 11- to 14-year-olds were randomized 1:1 to receive a 0-, 36-month or 0-, 12-month Pfizer MenABCWY schedule, which more closely aligns with current US MenACWY vaccination recommendations. Endpoints included serum bactericidal assay using human complement seroprotection rates (titers ≥ 1:8 or ≥1:16, depending on strain), seroresponse rates (≥4-fold increase from baseline titer), and geometric mean titers (GMTs). Safety was also assessed. Results: One month after the second Pfizer MenABCWY dose, serogroup A/B/C/W/Y seroprotection rates were 100% for the 0-, 36-month schedule and 96.6–100% for the 0-, 12-month schedule; seroresponse rates were 100% and 92.9–100%, respectively. GMTs generally trended higher with the 0-, 36-month schedule. Seroprotection rates through 24 months after the second dose of the 0-, 12-month schedule were 44.0–75.0% for serogroup B and 88.9–100% for serogroup A/C/W/Y). No safety issues were identified. Conclusions: These data support Pfizer MenABCWY dosing flexibility and utility within the current or possible future US meningococcal vaccination framework. Full article

Background/Objectives: This study evaluated the Omicron LP.8.1 variant-adapted BNT162b2 mRNA vaccine (LP.8.1-adapted BNT162b2). Methods: This analysis is part of an ongoing phase 3 open-label study evaluating the immunogenicity, safety, and tolerability of LP.8.1-adapted BNT162b2. Reported here are descriptive 2-week post-vaccination results in 18–64 -year-olds at high risk of severe COVID-19 and in ≥65-year-olds who received the Omicron KP.2-adapted COVID-19 vaccine ≥ 6 months previously. Primary immunogenicity endpoints included neutralizing antibody geometric mean titers (GMTs) against LP.8.1 and KP.2 at 2 weeks after vaccination and geometric mean fold rises from baseline to 2 weeks after vaccination. Results were compared with a historical control group of adults who received KP.2-adapted BNT162b2 in a previous study. Tolerability and safety were also assessed. Results: Overall, 104 participants received LP.8.1-adapted BNT162b2 (18–64-year-olds, n = 51; ≥65-year-olds, n = 53). Baseline neutralizing GMTs were higher in LP.8.1-adapted BNT162b2 recipients than in the historical control group of KP.2-adapted BNT162b2 recipients against both sublineages (248 vs. 157 against LP.8.1; 372 vs. 187 against KP.2). Serum-neutralizing LP.8.1 and KP.2 GMTs increased 2 weeks after vaccination with LP.8.1-adapted BNT162b2 (1752 against LP.8.1; 2104 against KP.2) and historical control groups (1555 and 2395, respectively), and across both age groups. Reactogenicity events with LP.8.1-adapted BNT162b2 were generally mild or moderate and occurred at generally similar frequencies in both age groups. Adverse events were reported in 4.8% of participants (all in 18–64-year-olds); no serious adverse events were reported. Conclusions: After 2 weeks of follow-up, and in a small sample size, LP.8.1-adapted BNT162b2 was immunogenic in ≥65-year-olds and ≥18-year-olds at high risk of severe COVID-19. The safety and tolerability profile for LP.8.1-adapted BNT162b2 was consistent with the current US prescribing information for BNT162b2 and that of other variant-adapted BNT162b2 vaccines (Clinicaltrials.gov Identifier: NCT07069309, registered 16 July 2025). Full article

Background: Influenza causes substantial morbidity in young children, particularly those aged 6–35 months. In this age group, optimisation of vaccine dose regimens remains important to ensure adequate immunogenicity while maintaining acceptable safety. This study evaluated the immunogenicity and safety of a full 0.5 mL dose of quadrivalent inactivated influenza vaccine (NBP607-QIV) in young children. Methods: This Phase 3, randomised, double-blind, active-controlled, multicentre study was conducted in Korea, Thailand, and Malaysia. Healthy children aged 6–35 months were randomised 2:1 to receive NBP607-QIV (0.5 mL) or control vaccine (0.25 mL). Immunogenicity was assessed using the haemagglutination inhibition assay. Primary endpoints were non-inferiority of NBP607-QIV versus Agrippal for seroconversion rate (SCR) and adjusted post-vaccination geometric mean titre (GMT) ratio against three shared strains. Immunogenicity against the additional B/Yamagata strain was evaluated according to Committee for Medicinal Products for Human Use (CHMP) criteria. Safety was assessed based on adverse events. Results: A total of 676 participants were randomised, and 675 were included in the safety set. Non-inferiority of NBP607-QIV versus control vaccine was demonstrated for SCR for all shared strains and for the adjusted GMT ratio for A/H1N1 and B/Victoria, but not for A/H3N2. Immunogenicity against the B/Yamagata strain met CHMP criteria for SCR and geometric mean ratio (GMR). Immunogenicity was consistent across prespecified subgroups, and the incidence of adverse events was comparable between groups, with no clinically meaningful safety concerns. Conclusions: NBP607-QIV administered at a 0.5 mL dose demonstrated acceptable immunogenicity and a safety profile comparable to that of a licensed trivalent influenza vaccine in children aged 6–35 months, supporting its use in this paediatric population. Full article

Background: Annual influenza vaccination is a WHO-recommended strategy for preventing seasonal influenza and its associated severe complications in older adults. Nevertheless, influenza vaccine effectiveness is often reduced in the elderly population and there remains an ongoing debate regarding whether repeated vaccination attenuates immune response. Methods: We conducted a prospective observational study to estimate the trivalent inactivated influenza vaccine-induced antibodies in older adults vaccinated for two consecutive years (2022–2023 and 2023–2024) and those with vaccines administered in a single season (2023–2024). Serum samples were collected concurrently with vaccination and at 30 and 90/180 days post-vaccination for hemagglutination inhibition (HAI) tests. Results: The participants administered two consecutive vaccinations had markedly higher pre-vaccination geometric mean titers (GMTs) and seroprotection rates for influenza A/H1N1 and A/H3N2. However, no intergroup differences were observed for H1N1, H3N2 or B/Victoria strains at 30, 90, or 180 days post-vaccination. At 30 days post-vaccination, participants with two consecutive influenza vaccinations showed significantly lower fold rises against the three strains and seroconversion rates (SCRs) for H1N1 and H3N2. The results of the subgroup analyses were largely consistent with the primary findings, with the exception of the A/H1N1 strain among individuals with pre-vaccination titers <1:10 at day 30. Conclusions: Immune responses vary by antigen type, and the influenza vaccine induces comparable serological response in the elderly, irrespective of their prior vaccination history. Full article