Search Results (129)

Background: Pneumococcal conjugate vaccines (PCVs) prevent severe disease in children, but high costs limit access. PCV10-SII (PNEUMOSIL), a 10-valent PCV prequalified by the World Health Organization (WHO) in 2019, offers a cost-effective alternative. This study assessed its safety and immunogenicity in Vietnamese children aged 6 weeks–24 months. Methods: An open-label, single-arm study enrolled 304 children in three age groups: 6 weeks–6 months (n = 151), >6–12 months (n = 76), and >12–24 months (n = 77). Participants received two or three doses. Safety was evaluated through immediate reactions, adverse events (AEs), serious adverse events (SAEs), and withdrawals. Immunogenicity was measured 28 days after the final dose using serotype-specific IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA) titers, and seroresponse rates. The trial was approved by the IRB of the National Ethics Council (code: No. 75/CN-HĐĐĐ on date 4 June 2021) and was registered with ClinicalTrials.gov, NCT05140720. Results: Of 304 enrolled participants, 294 (96.7%) completed follow-up. No immediate adverse events or serious adverse events occurred. Unsolicited adverse events were reported in 17%, mainly respiratory, while serious adverse events occurred in 4%. Mild local/systemic reactions (e.g., injection site pain, crying) resolved without sequelae. Immunogenicity was strong, with GMCs 1.8–9.11 µg/mL, GMTs 277.8–22,342, and seroresponse rates >90% for 9 of 10 serotypes, serotype 6B demonstrated a slightly lower seroresponse rate of 88.6%. Conclusions: PCV10-SII demonstrated favorable safety and robust immunogenicity, supporting its inclusion in national immunization programs as an affordable option for pneumococcal disease prevention. Full article

Salmonella enterica remains a major food safety concern in poultry, and processing-related stress can influence its survival and persistence. This study evaluated the phenotypic expression of S. enterica serotypes Kentucky (SK), Infantis (SI), Schwarzengrund (SS), and Typhimurium (ST) following antimicrobial and temperature stressors. A pre-harvest isolate of each serotype was gradually exposed to increasing concentrations of peracetic acid (PAA) and quaternary ammonium compounds (QACs), starting at 40 ppm and 1 ppm, respectively, until minimum inhibitory and bactericidal concentrations (MICs/MBCs) were established. Stressed cells were then subjected to cold (4 °C, 60 min) and heat (55 °C, 6 min) shock and assessed for sanitizer tolerance, biofilm formation and recovery, and antibiotic resistance. Sanitizer tolerance after daily conditioning varied among S. enterica serotypes, with ST and SK showing the highest tolerance to PAA and QACs, respectively. The tolerance of PAA variants increased by 10–20 ppm and QAC variants by 2–8 ppm following stress exposure. The double-stressed variants of ST significantly (p < 0.05) formed more biofilm than the control after PAA, whereas no significant differences were observed among the variants for other serotypes. Biofilm recovery was higher for the stressed variants of SI and SS (p < 0.05) following PAA stress but remained the same across all serotypes after QAC stress. QAC-stressed variants showed more phenotypic changes across the antibiotics tested. Notably, the stressed variants of SK, SS, and ST displayed increased MICs, including a 2- to 4-fold rise in azithromycin for the SK and ST variants. There was an increase in the MICs of ceftriaxone and nalidixic acid for some SK and SS variants. These findings suggest that environmental stress can significantly enhance the tolerance, survival, and persistence of S. enterica. Full article

Riemerella anatipestifer (R. anatipestifer) is a pathogenic bacterium belonging to the genus Riemerella within the family Flavobacteriaceae, which has multidrug resistance (MDR) and can cause high pathogenicity in waterfowl. The aim of this study was to investigate the antimicrobial resistance and genomic characteristics of R. anatipestifer strains isolated from several regions of China from 2023 to 2024. Two strains were selected for challenge tests, and virulence protection tests were conducted on florfenicol-resistant and florfenicol-sensitive strains. A total of 88 strains of R. anatipestifer were collected from the Shandong, Jiangsu, Guangdong, Hebei and Henan regions. The results showed that the 88 strains included serotypes 1, 2, 5, 6, 7 and 10. Serotype 5 was the most prevalent in the Shandong region. All strains were multidrug-resistant, with the hexaresistance accounting for the highest proportion (42.1%). A total of five resistance genes (tet(X), floR, ermF, qnrS, rmtB) and seven virulence genes were found (ompA, camp, AS87_04050, SIP, Fur, TbdR1, luxE). The challenge test showed that the LD₅₀ of RA12 was 2.75 × 10⁷ CFU/mL, and that of RA26 was 2.57 × 10⁷ CFU/mL. Phylogenetic tree analysis revealed that strain RA26 was closely related to strain 20190403E1-1, and strain RA16 was closely related to strain JW1. In addition, serotypes 2 and 7 identified in this study have been undergoing clonal transmission in China. Virulence protection tests indicated that the results of in vitro drug susceptibility tests were consistent with the therapeutic effects after in vivo treatment, and no R. anatipestifer was found in the visceral tissues of surviving ducklings. This study provides a reference for the rational use of antibiotics. Full article

Background/Objectives: Shigella is the leading bacterial cause of diarrheal disease worldwide. Although multiple vaccine candidates are under development and in clinical trials, no Shigella vaccine is currently available on the market. Shigella comprises four species: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. S. flexneri has been recognized as the most prevalent species, particularly in low- and middle-income countries (LMICs), and the top serotypes are S. flexneri 2a, 3a and 6. Conversely, S. sonnei has a single serotype and predominates in high-income countries (HICs). Invasion plasmid antigen B (IpaB) is a critical virulence factor of Shigella type III secretion system (T3SS) that is highly conserved across Shigella serotypes. Here, we report the development of a Shigella quadrivalent O-polysaccharide-IpaB conjugate vaccine candidate (IVT Shigella-04). Methods: IVT Shigella-04 contains O-polysaccharides (O-PS) from S. flexneri 2a, 3a, 6, and S. sonnei, each individually conjugated to recombinantly expressed IpaB as the carrier protein using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry. The immunogenicity of IVT Shigella-04 was evaluated in a rabbit immunization model. Results: Baseline (day 0) IgG concentrations were low for all four Shigella serotypes (<0.5 µg/mL). Following two doses on day 0 and day 28 (2.5 µg of each conjugate per dose; total 10 µg), IgG geometric mean concentrations increased significantly (p < 0.001) by day 42, reaching 67.96 µg/mL (2a), 91.56 µg/mL (3a), 371.31 µg/mL (6), and 11.00 µg/mL (sonnei). Consistently, serum bactericidal activity (SBA) at day 42 increased 13-fold (2a), 34-fold (3a), 63-fold (6), and 224-fold (sonnei) relative to baseline (day 0). Conclusions: IVT Shigella-04 elicited robust serotype-specific humoral and functional immune responses in preclinical models, supporting its further development toward clinical evaluation. Full article

Background: Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020–2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6–4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0–1.9), and winter (aOR 1.7, 95%CI: 1.5–2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5–2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization. Full article

Background/Objectives: American Indian/Alaska Native individuals exhibit a higher prevalence of carriage of Streptococcus pneumoniae and are at increased risk of invasive pneumococcal disease compared with the general US population, driven by persistent inequities in health determinants. Although the use of pneumococcal vaccines has reduced carriage of vaccine serotypes, the prevalence of carriage of non-vaccine serotypes has increased. Methods: This study was a descriptive subgroup analysis of the PNEU-DAY study (NCT03547167; EudraCT 2017-004915-38). Safety, tolerability, and immunogenicity of sequential administration of either V114, a 15-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV (PCV13), followed 6 months later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), were evaluated in pneumococcal vaccine-naïve American Indian adults with or without pre-defined risk factors for pneumococcal disease. Polymerase chain reaction testing assessed nasopharyngeal/oropharyngeal carriage of S. pneumoniae. Results: Following administration of PCV and PPSV23, the proportions of participants with adverse events were generally comparable between vaccination groups. V114 and PCV13 were immunogenic for all respective vaccine serotypes, with V114 inducing robust immune responses to the two additional serotypes not included in PCV13 (22F and 33F), based on opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations at 30 days post-vaccination. Sequential administration with PPSV23 was immunogenic in both vaccination groups. Nasopharyngeal/oropharyngeal carriage of S. pneumoniae was observed in 16.7% to 22.6% of American Indian participants across the study timepoints. Conclusions: V114 was well tolerated and immunogenic for the 15 serotypes in V114 when administered either alone or followed by PPSV23. Use of V114 has the potential to expand serotype coverage and protect against pneumococcal disease resulting from serotypes absent in PCV13 among American Indian adults. Full article

Objective: Cardiac hypertrophy, a key feature and predisposing factor of heart failure, is mainly controlled by complex signaling cascades. Growth differentiation factor 6 (GDF6) plays critical roles in cell growth and cardiovascular homeostasis; however, its role and underlying mechanisms in cardiac hypertrophy remain unclear. Methods: Mice were intravenously injected with adeno-associated virus serotype 9 to overexpress and knock down GDF6 in murine hearts and then exposed to transverse aortic constriction (TAC) surgery to generate pressure overload-induced cardiac hypertrophy. Echocardiographic, histological, and molecular analyses were performed to decipher the alterations to cardiac hypertrophy. In addition, neonatal rat ventricular myocytes (NRVMs) were isolated and stimulated with phenylephrine (PE) to further validate its involvement in hypertrophic growth of cardiomyocytes. Results: GDF6 expression was elevated in murine hearts and NRVMs by ROS production under hypertrophic stimuli. GDF6 knockdown aggravated, while GDF6 overexpression attenuated, pressure overload-induced cardiac hypertrophy, inflammation, and dysfunction in vivo. Meanwhile, we found that GDF6 also prevented PE-induced hypertrophic growth of NRVMs in vitro. Mechanistically, GDF6 activated AMPKα to exert cardioprotective effects, and AMPKα inhibition significantly blocked the anti-hypertrophic effects of GDF6. Further studies showed that GDF6 activated AMPKα through the cAMP/Epac1 pathway, and that Epac1 knockdown abolished the protective effects of GDF6 against TAC- or PE-induced cardiac hypertrophy in vivo and in vitro. Conclusions: In general, our findings, for the first time, define GDF6 as a negative regulator of cardiac hypertrophy and show that supplementation of GDF6 may be of great therapeutic interest for heart failure. Full article

Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a hyper-expression vector system for the expression of L1 proteins of four major HPV serotypes—HPV 6, 11, 16, and 18. Methods: HPV L1 proteins were expressed in Trichoplusia ni (Hi5) insect cells via a hyper-expression baculovirus vector system. Following cell lysis using a microfluidizer, VLPs were purified through a two-step chromatographic process. Particle morphology was characterized using transmission electron microscopy and dynamic light scattering. Immunogenicity was evaluated using a murine model; mice received three intramuscular injections of the purified quadrivalent VLPs. The resulting IgG and neutralizing antibody responses were compared with those elicited by the commercial quadrivalent vaccine, Gardasil. Results: The L1 proteins from HPV 6, 11, 16, and 18 were successfully expressed at high levels in Hi5 cells, forming uniformly sized VLPs with hydrodynamic diameters of 50–60 nm. The average production yield of the quadrivalent VLPs exceeded 40 mg/L, an improvement over conventional yields. The candidate VLPs elicited strong HPV-specific IgG and neutralizing antibody responses in mice, comparable to those induced by Gardasil. Conclusions: The hyper-expression baculovirus vector system enables high-yield production of HPV L1 VLPs with desirable structural and immunogenic properties. This approach holds promise for the cost-effective and scalable manufacturing of next-generation HPV VLP vaccines, facilitating broader global access to HPV immunization. Full article

Bluetongue virus belongs to the Reoviridae family, which causes morbidity in ruminants. Herein, we report the full-length genome sequence of a recombinant BTV strain of serotype 1 (YNDH/103/2013) isolated from sentinel cattle in Yunnan Province, China, in 2013. To identify and understand the characteristics of YNDH/103/2013, we screened closely related viruses using Simplot 3.5.1 software and conducted verification via phylogenetic analysis using MEGA 11.0.13 software. Phylogenetic analysis and segment examination showed that the YNDH/103/2013 strain likely originated from multiple recombination events involving prevalent strains such as Y863, NRT37/ABT/HSR, and YTS-4 in China and India. The genome of BTV-1/YNDH/103/2013 derives from at least three reassortments with these strains, showing recombination breakpoints mainly in segments 4, 6, 8, and 9. This study improves our understanding of the origin and spread of BTV-1 in China. Full article

Enteroviruses of the Picornaviridae family are transmitted primarily by the fecal–oral route. Transmission may occur following hand contact with contaminated fomites and subsequent ingestion of virus conveyed to the mouth by the contaminated hand. The persistence of these viruses on fomites likely plays a role in this transmission scenario. Six echoviruses (1, 2, 3, 5, 6, and 7) that cause frequently reported clinical cases in the United States were studied, along with poliovirus type 1 vaccine strain LSc-2ab. The infectivity half-lives of the enteroviruses deposited on vinyl tile coupons in a 10% fecal solution ranged from 1.7 to 12.6 h. The echovirus serotypes most commonly associated with reported infections persisted longer on the vinyl tiles than the less commonly reported types. This increased persistence on surfaces may favor the transmission of these echoviruses through the fecal–oral route. These results inform the future selection of appropriate model enteroviruses for challenging newly formulated and eco-friendly disinfectants or other strategies in infection prevention and control for enteroviruses. Full article

Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue patients at the General Hospital of Colima (January–August 2024). Clinical features, laboratory parameters, and outcomes were compared between survivors and non-survivors. Among 201 hospitalized patients, 6 (3.0%) died. All deceased patients presented with generalized seizures, polyserositis (pleural effusion and/or ascites), and required mechanical ventilation. Contrary to classical patterns, they did not have severe thrombocytopenia. Instead, they showed significantly higher white blood cell counts and notably increased levels of serum urea and BUN, suggesting early renal impairment. ROC analysis indicated that BUN (AUC 0.904) and urea (AUC 0.906) were good to excellent discriminators of mortality. During 2024, with an increase in DENV-3 circulation, mortality was associated with neurological and systemic complications, including seizures and polyserositis, as well as biochemical evidence of renal dysfunction—but not with severe thrombocytopenia. These findings challenge current paradigms and highlight the need for early recognition of atypical clinical patterns. Full article

Introduction: An effective vaccination strategy requires monitoring serotype changes by geography and age. This study analyzed Streptococcus pneumoniae serotypes in healthy children under 6 years of age vaccinated with PCV10 in Bulgaria from October 2021 to May 2025. Methods: A total of 569 children were screened for the lytA and cpsA genes viareal-time polymerase chain reaction (real-time PCR). Positive samples were typed using relevant kits, and 76 serotypes/serogroups of S. pneumoniae were identified. Results: Nasopharyngeal swabs from 232 children (40.8%) were found to carry S. pneumoniae, and a total of 255 serotypes were detected, with 19B/19C (17.2%), 6C (10.7%), and 15B/15C (9.8%) being the most prevalent. Of these, 91 serotypes (15.9%) were included in at least one vaccine, while the remaining 164 serotypes (25.4%) were not. The carriage rate reduced to 22% in 2023 but increased to 47% in 2024. Overall, younger children had lower carriage rates (p < 0.05), with serotype 6C being more common in children under 12 months of age (25%). Approximately 9.1% of pneumococcal carriage cases involved co-detected serotypes, with significantly higher co-detection rates for 19B/19C, 15B/15C, 10B, 10F/C, 23B, 7C/40, 23A, and 24A compared with mono-detection rates (p < 0.05). Conclusions: 19B/19C, 6C, 15B/15C, and 19A were identified as the main serotypes. Children over 3 years of age were also more likely to carry multiple pneumococci. These findings emphasize the need to reassess childhood vaccination strategies to curb the spread of antibiotic-resistant serotypes. Full article

The introduction of pneumococcal conjugate vaccination (PCV) into the Argentinian Childhood National Immunization Program in 2012 marked a significant milestone in public health. Our study aims to assess the impact of this intervention on pneumococcal meningitis cases, serotype distribution, and antimicrobial resistance among pediatric populations from 2013 to 2023. Specifically, we compared the early post-PCV period (2013–2014) to the late post-PCV period (2022–2023). A total of 333 pneumococcal isolates were analyzed between 2013 and 2023. Gold standard pneumococcal serotyping was performed to identify the serotypes associated with infection in children < 6 years in Argentina, and the agar dilution method was carried out to determine their profiles to antimicrobial agents. Our findings underscore the importance of PCV implementation, revealing notable shifts in pneumococcal epidemiology over the study period. The proportions of serotypes 1 (6.7% to 0.0%), 5 (5.6% to 0.0%), and 14 (7.8% to 1.8%) decreased, whereas the proportions of serotypes 10A (3.3% to 10.7%), 15B/C (2.2% to 10.7%), and 24B (0.0% to 8.9%) increased. The top five rated serotypes in the 2022–2023 period were serogroup 24 (21.4%), 10A (10.7%), 15B/C (10.7%), 23B (7.1%), and 12F (5.4%). Regarding antimicrobial resistance, we found that a total of 115/311 isolates (37%) were not suceptible to penicillin, and 2.9% were not suceptible to cefotaxime. Twenty-five percent of the isolates were microbial drug resistant, with resistance to penicillin, erythromycin, tetracycline/doxicycline, and/or cotrimoxazol. Among the PCV13 serotypes, 19A remained the most commonly associated with MDR. The non-PCV13 serotypes, particularly 24F, 24A, and 24B, were prevalent among MDR isolates. The observed trends demonstrate the need for the continued expansion of pneumococcal vaccination policies, including consideration for vaccines offering enhanced indirect protection, thereby extending benefits beyond the pediatric population to encompass adults as well. Such strategies are pivotal in reducing the burden of pneumococcal disease and safeguarding public health. Full article

Background: In the Democratic Republic of Congo (DRC), the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to reduce pneumococcal-related morbidity and mortality. The aim of this study was to determine the proportion of pneumonia and meningitis cases and deaths prevented in children under five following the introduction of this vaccine. Methods: This is a systematic review. We synthesized findings from studies carried out in the DRC between 2011 and 2023. We searched scientific articles, published and unpublished doctoral theses and conference proceedings. Only papers written in French or English and those reporting the results of original analytical studies were selected. We assessed the direct effect of PCV13 by calculating the proportion of infections avoided, using Odds Ratios or prevalence ratios related to infection or pneumococcal carriage. Results: Four studies were included in this review. Regarding pneumococcal carriage, when children received three PCV13 doses, the prevalence of carriage was reduced by 93.3% (95% CI: 86.3 to 96.6%), while a single dose did not significantly reduce the prevalence of carriage compared with children who had not received any dose. Concerning pneumonia prevention, three doses of PCV13 prevented 66.7% (95% CI: 37.2 to 82.2) of cases among vaccinated children. The proportion of meningitis attributable to S. pneumoniae prevented was 75.0% (95% CI: 6% to 93.3%) among children vaccinated with PCV13. S. pneumoniae serotypes 19F and 23F were the most frequent causes of invasive pneumonia in children. Serotypes 35B/35C, 15B/C, 10A and 11A/D were the most frequently identified causes of morbidity in Congolese children. In 2022, with PCV13 vaccination coverage at 79.0%, an estimated 113,359 cases of severe pneumonia and 17,255 pneumonia-related deaths were prevented in the DRC, with 3313 cases and 1544 deaths attributable to pneumococcal meningitis prevented. Conclusions: There is clear, but scattered, evidence of reduced colonization by S. pneumoniae and hospital admissions due to pneumococcal pneumonia and meningitis. The results also show that S. pneumoniae serotypes 35B/35C, 15B/C, 10A and 11A/D not included in PCV13 were the main cause of pneumococcal disease in unvaccinated or under-vaccinated children. These data support the need to continue improving vaccination coverage among children who are unvaccinated or incompletely vaccinated with PCV13 to reduce the burden of pneumococcal infections in the DRC. Full article

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24–27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule. Full article