Search Results (678)

The increasing demand for monoclonal antibody (mAb) therapeutics has intensified the need for more efficient and consistent biomanufacturing processes. We present a data-driven, machine-learning (ML) approach to exploring and predicting upstream yield behavior. Drawing on industrial-scale batch records for a single mAb product from a contract development and manufacturing organization, we applied regression models to identify key process parameters and estimate production outcomes. Random forest regression, gradient boosting machine, and support vector regression (SVR) were evaluated to predict three yield indicators: bioreactor final weight (BFW), harvest titer (HT), and packed cell volume (PCV). SVR outperformed other models for BFW prediction (R² = 0.978), while HT and PCV were difficult to model accurately with the available data. Exploratory analysis using sequential least-squares programming suggested parameter combinations associated with improved yield estimates relative to historical data. Sensitivity analysis highlighted the most influential process parameters. While the findings demonstrate the potential of ML for predictive, data-driven yield improvement, the results should be interpreted as an exploratory proof of concept rather than a fully validated optimization framework. This study highlights the need to incorporate process constraints and control logic, along with interpretable or hybrid modeling frameworks, to enable practical deployment in regulated biomanufacturing environments. Full article

The intensity and prevalence of different gastrointestinal nematode species vary across regions worldwide. Oesophagostomum radiatum commonly shows a high occurrence in young cattle. O. radiatum causes anaemia, hypoproteinaemia, and immunopathological changes in the large intestine wall, impairing calves’ body weight gain. This study aimed to assess the impact of natural O. radiatum infection on haematological parameters and immune responses in 23 Nellore calves, considering sex-based differences. Assessments included Oesophagostomum egg count (EPG), worm count, packed cell volume (PCV), total plasma protein, histopathological and immunohistochemistry analyses. A large number of parasites attached to the colon mucosa were observed, along with massive nodule formation and haemorrhagic lesions, mainly within a 20–30 cm-long segment adjacent to the nodules. The maximum mean egg shedding was approximately 165 EPG for males and 173 EPG for female calves; however, males presented a significantly higher worm count (969 ± 200.5) than females (460 ± 99.5). There were significant positive correlations between the total O. radiatum worm count and O. radiatum EPG for both female and male calves. Significant negative correlations were observed between the total O. radiatum worm count and PCV in female calves. Our results demonstrated that natural O. radiatum infection in Nellore calves induced marked immunopathological alterations, including chronic inflammatory responses that impaired intestinal function. Sex-related differences suggested that female calves may develop more effective tissue responses. These findings emphasise the economic impact of subclinical infections and reinforce the importance of control strategies to minimise productivity losses in cattle. Full article

Background/Objectives: Maternally derived antibody (MDA) levels of porcine circovirus 2 (PCV2) may eventually interfere with humoral response and vaccination efficacy. This study aimed to evaluate the efficacy of a ready-to-use PCV2d and Mycoplasma hyopneumoniae combined vaccine in piglets with different PCV2 MDA levels at vaccination in an experimental inoculation with a heterologous viral genotype. Methods: Forty-eight piglets were allocated into vaccinated (V) and non-vaccinated (NV) groups with high (H) and low (L) PCV2 MDA subgroups (H-V, H-NV, L-V, L-NV). At 3 weeks of age, the piglets received either one dose of vaccine or placebo. Five weeks later, all animals were intranasally challenged with a PCV2b inoculum. Body weight was registered at different time points. Blood samples, peripheral blood mononuclear cells and tracheobronchial lymph nodes (TBLN) were collected and used to assess viraemia, viral load, humoral and cellular responses and histological lesions. Results: The V group showed higher PCV2 antibody levels from challenge onwards, along with a lower percentage of viraemic pigs and reduced viral load in serum at 2 and 3 weeks post-challenge (wpc) and in TBLN tissues compared to the NV group. The H-V group had the highest antibody levels post-challenge, showed no detectable viraemia and had a lower overall amount of virus in tissues. The NV group (especially H-NV) exhibited increased levels of IFN-γ, IFN-α and TNF-α post-challenge. Conclusions: The tested vaccine elicited humoral and cellular immune responses and reduced viral presence in serum and tissues, demonstrating efficacy in a PCV2 subclinical infection model despite high MDA levels at the time of vaccination. Understanding both humoral and cellular immune responses according to different MDA levels can help design more effective vaccination strategies against PCV2. Full article

Background: Porcine circovirus type 2 (PCV2) is the primary pathogen responsible for postweaning multisystemic wasting syndrome (PMWS) and related diseases, leading to significant economic losses in the global pig industry. Methods: This study conducted a thorough epidemiological survey between 2022 and 2024, gathering 6600 samples from 24 large-scale pig farms in Hubei Province. On the basis of these findings, the immune response and economic benefits of two representative commercial PCV2 subunit vaccines, recombinant baculovirus CP08 and Ingelvac CircoFLEX^®, were assessed in a modern fattening farm in Xiangyang city. Results: The results indicated no detection of viral antigens in sows; however, weaned piglets and fattening pigs presented high positivity rates, with 8-week-old nursery pigs identified as the peak period for infection. Both vaccines significantly improved average weight gain and reduced antigen positivity, with Ingelvac CircoFLEX^® demonstrating superior viral control and economic returns. Conclusions: This study offers valuable scientific and practical guidance for PCV2 control strategies and vaccine selection in Hubei and comparable regions. Full article

Despite the widespread use of Porcine circovirus type 2 (PCV2) vaccination, subclinical infection persists and remains a concern due to its economic impact. Therefore, continuous herd-level monitoring is essential to assess the dynamics of this infection on farms and minimize its impact. This study evaluated the applicability of a loop-mediated isothermal amplification (LAMP) assay for PCV2 detection in serum, air, and surface samples collected under field conditions. In addition, a simplified Direct LAMP protocol, omitting DNA extraction, was compared with quantitative PCR (qPCR) as the reference method. A total of 360 samples from PCV2 vaccinated and unvaccinated fattening farms were analyzed. Diagnostic performance was assessed in terms of sensitivity, specificity, predictive values, and concordance with qPCR, using Cohen’s kappa coefficient (κ). LAMP showed higher agreement with qPCR (κ = 0.52) than Direct LAMP (κ = 0.16). Serum samples provided the most reliable results when DNA extraction was performed, reaching substantial agreement with qPCR (κ = 0.76). However, Direct LAMP applied directly to serum was negatively affected by inhibitory substances, resulting in a significant drop in sensitivity. In contrast both air and surface samples yielded comparable results between LAMP and Direct LAMP, without the need for DNA extraction. Notably, LAMP-based assays detected PCV2 circulation earlier than qPCR, particularly in environmental samples. These findings demonstrate the potential of LAMP as a practical alternative to qPCR for PCV2 monitoring. While DNA extraction remains essential for reliable detection in serum, Direct LAMP represents a promising strategy for environmental surveillance, enabling rapid, low-cost, and on-farm diagnostics. Full article

Durum wheat is a vital wheat species cultivated worldwide for human consumption, ranking second to bread wheat. The Ethiopian durum wheat allele pool shows wide gene diversity; however, limited improvement work has been done to exploit this diversity. Thus, this study aimed to assess the genetic variability, heritability, and interrelationship among different phenotypic traits in 210 recombinant inbred lines (RILs) using an alpha lattice design with two replications. The analysis of variance revealed a significant difference for all the measured traits. The phenotypic coefficient of variation (PCV) was greater than the genotypic coefficient of variation (GCV) for all the characters, which reflects that the existing range of variability within the genotypes was not only due to the varying influence of genotype but also the environment. A correlation analysis disclosed that grain yield was positively related to the traits of plant height and 1000-kernel weight, suggesting that selecting these traits could enhance yield. Path analysis revealed that days to booting, maturity, and 1000-kernel weight directly affect grain yield. Among the measured traits, early developmental traits revealed higher broad-sense heritability. The findings of this study highlight high genetic diversity among Ethiopian durum wheat genotypes, opening up opportunities to integrate these materials into future wheat-breeding programs through introgression with other germplasm sources in Ethiopia and beyond. Full article

Restrictions on adding antibiotics to animal diets have posed challenges in managing gut pathogens, emphasizing the significance of effective non-antibiotic growth promoters to maintain animal health and productivity. This study assessed the efficacy of hydroxamic acid (HA), derived from local maize varieties, as a non-antibiotic growth promoter in broilers. Among 10 different maize varieties, the Azam variety yielded the highest HA concentration (35 ± 7 μg/g of roots), as quantified by high-performance liquid chromatography (HPLC). In vitro antimicrobial assays demonstrated the lowest minimum inhibitory concentration (MIC) of 0.022 mg for Azam-derived HA against pathogenic E. coli. To further assess in vivo efficacy, 108 birds were allocated at random to six treatment groups. The treatments include birds fed a basal diet without an E. coli challenge (negative control); an antibiotic-treated group challenged with E. coli and treated with enrofloxacin at a dosage of 5 milligrams (mg) per kilogram (kg), administered orally once daily from day 5 post-infection (dpi) for 7 consecutive days (standard); broilers challenged with E. coli and supplemented with a basal diet with HA at concentrations of 1, 10, or 100 mg/kg of feed from 5 dpi for one week (HA 1 mg, HA 10 mg, and HA 100 mg, respectively); and broilers challenged with E. coli without enrofloxacin/HA (positive control). The results demonstrated that birds fed a diet supplemented with the HA-100 mg improved the body weight (BW) and feed conversion ratio (FCR) compared to the positive control group. There were no significant differences (p > 0.05) observed for BW and FCR observed for the broilers fed on the standard and HA 100 mg groups. The addition of HA at 100 mg improved (p < 0.05) the hemoglobin (Hb) and packed cell volume (PCV) and reduced (p < 0.05) levels of malondialdehyde (MDA) compared to positive control group. A significantly low carcass weight (p < 0.05) was shown for positive control birds compared to other groups. Our findings indicate that maize-derived HA presents a phytogenic alternative to antibiotics by controlling enteric pathogens and improving health and performance affected by E. coli infection in broilers. Full article

Porcine circovirus type 3 (PCV3), initially identified in the United States in 2016, is associated with multisystemic inflammation, myocarditis, reproductive failure in sows, and growth retardation in piglets, posing a significant economic threat to the swine industry. In this study, prokaryotic-expressed recombinant PCV3 Cap protein was used to immunize mice and rabbits. A monoclonal antibody (mAb 4G1) was generated through hybridoma technology, targeting a novel linear epitope (³⁷DYYDKK⁴²) within the first β-sheet of the Cap structure. This epitope exhibits high conservation (99.35%, 1239/1247) based on sequence alignment analysis, and residues 39 and 42 are critical residues affecting mAb binding. Subsequently, using rabbit polyclonal antibody (pAb) as the capture antibody and mAb 4G1 as the detection antibody, a double antibody sandwich ELISA (DAS-ELISA) method was developed. The assay demonstrates a cut-off value of 0.271, a detection limit for positive pig serum is 1:800, and shows no cross-reactivity with other swine pathogens. Intra- and inter-assay coefficients of variation were <10%, with a linear detection range for Cap protein down to 3.4 ng/mL. The coincidence rate between the DAS-ELISA and qPCR was 93.33% (70/75) for PCV3 detection in serum, with a kappa value of 0.837. This study establishes a simple, sensitive, and operationally efficient DAS-ELISA and provides a reference for monitoring PCV3 infection in swine herds. Full article

Background: Personalized cancer vaccines (PCVs) are a promising form of cancer immunotherapy, capable of eliciting robust neoantigen-specific immune responses. However, cancer neoantigens are variable in terms of immunogenicity, and PCVs may be less effective when targeting weak neoantigens. Strong and durable immune responses are also likely to be critical for vaccine efficacy. Interleukin-7 (IL-7) is a common gamma-chain cytokine known to support T cell development and survival, and a long-acting form of recombinant human IL-7 fused with hybrid Fc (rhIL-7-hyFc) has shown potential to enhance immune responses in early-stage clinical trials. Methods: In this study, we evaluated the ability of rhIL-7-hyFc to serve as a molecular adjuvant to a DNA PCV in the E0771 murine breast cancer model. Results: We found that the combination of rhIL-7-hyFc and DNA PCV treatment prolonged neoantigen-specific CD8+ T cell responses, improved functional memory as measured based on in vivo cytotoxicity, and increased the number of neoantigen-specific tumor-infiltrating lymphocytes (TILs), resulting in improved prophylactic tumor protection and durable memory responses. Conclusions: Our findings support the potential of rhIL-7-hyFc to enhance the efficacy of PCVs and suggest clinical utility for adjuvant rhIL-7-hyFc in cancer immunotherapy. Full article

Background/Objectives: This study analyzes the epidemiology of invasive pneumococcal disease (IPD) and the dynamics of Streptococcus pneumoniae (SP) serotypes in the Comunidad Valenciana (CV) region, Spain, over a 10-year period (2014–2024), with particular focus on vaccine coverage of PCV13 compared to the newer PCV20 and PCV21 formulations. Methods: A total of 2.014 isolates of SP obtained from sterile fluids were included, with available serotype, demographic data, and vaccination status, which were collected from the Epidemiological Surveillance System (AVE) and the Microbiological Surveillance Network of the CV region (RedMIVA). Results: Overall vaccination coverage was low (22.4%), with the highest rates observed in children under 10 years (78%) compared to only 16% in those aged 10–64 years and 22% in those over 64. Serotype distribution revealed 120 distinct serotypes, with serotype 8 (17.6%) and serotype 3 (14.7%) being the most frequent. Serotype 8 predominated among unvaccinated individuals, while serotype 3 remained highly prevalent despite inclusion in PCV13. Other relevant serotypes included 22F, 9N, 19A, 6C, and 23A. Temporal analysis showed that serotype 3 has continued to increase in recent years, whereas serotype 8 rose during the pandemic period but has remained stable in the most recent interval, while 19A, 15A, and 11A significantly declined. Among serotypes with <2% incidence, some, such as 4, 24F, and 38, showed upward trends. Conclusions: The findings suggest that PCV20 currently provides broad coverage of dominant serotypes, but PCV21 may offer advantages should serotypes like 23A, 9N, or 15A increase further due to serotype replacement. Continuous epidemiological surveillance is essential to guide evidence-based vaccine policy and anticipate future vaccine reformulations. Full article

Background: COPD and stable angina are common in older adults, increasing the risk of respiratory and cardiovascular complications. Pneumococcal vaccination is recommended to reduce this burden. This study evaluated the 10-year impact of 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (COPD), COPD exacerbations, hospitalizations, and survival in this cohort. Methods: A total of 483 male patients with COPD and/or stable angina received a single dose of PCV13 and were divided into three groups: Group 1 (n = 140): vaccinated with COPD; Group 2 (n = 167): vaccinated with COPD and stable angina; and Group 3 (n = 176): unvaccinated with COPD. Primary endpoints were CAP cases, COPD exacerbations, and hospitalizations; the secondary endpoint was survival. Analysis used generalized linear models, Cox regression, and Kaplan–Meier survival curves. Results: PCV13 significantly reduced CAP in patients with COPD alone but not in those with comorbid angina. Although CAP, exacerbations, and hospitalizations increased over time, vaccinated groups consistently showed lower rates than the unvaccinated group. Survival was higher in both vaccinated groups over 10 years. Conclusions: PCV13 was associated with a reduced risk of CAP, COPD exacerbations, hospitalizations, and improved survival in older adults with COPD and stable angina. These findings support the vaccine’s potential to improve outcomes in multimorbid populations and its inclusion in clinical guidelines and adult immunization programs for high-risk older adults. Full article

Porcine circovirus 2 (PCV2) is still infecting pigs after almost 20 years of massive vaccination all over the world. Vaccines are highly effective at counteracting the clinical signs of systemic disease caused by PCV2 and can significantly reduce the number of subclinically infected pigs. However, current vaccination programs based on one single dose in piglets are insufficient to prevent infection in a proportion of animals. Moreover, systematic vaccination of the herd changes viral epidemiology and, consequently, can cause modifications in infection timing. Such a scenario may prompt intrauterine and piglet early infections, thus facilitating viral circulation even before vaccination takes place. Considering the demonstrated high vaccine efficacy, it would be legitimate to explore the possibility of eliminating PCV2 from swine herds, but only one attempt to eliminate the virus from a herd has been published so far. The present speculative review evaluates the existing scientific literature regarding the feasibility of getting rid of this virus under commercial farm conditions. The use of PCV2 vaccination in all swine populations within a herd and the implementation of regional or national control programs are foreseen as compulsory for the eventual successful elimination of this endemic viral infection. Full article

Porcine circovirus 2 (PCV2) is one of the most widespread immunosuppressive viruses, impairing the protective efficacy of vaccines in pig herds. Previous studies have shown that PCV2 infection reduces the generation of immune memory and antibody secretion induced by vaccination in hosts. In this study, we used single-cell mRNA sequencing of mice splenic cells to show that PCV2 infection decelerates the differentiation of light zone germinal center (GC) B cells into memory B cells and plasma cells. We found that, although PCV2 infection led to lymphocyte depletion in the spleens of mice, the remaining splenic B cells were activated by the infection. The percentage of naïve B cells in PCV2-infected mice decreased mainly due to differentiation rather than death. Meanwhile, the percentages of memory B cells and plasma cells increased without significant enhancement of functional gene expression. Focusing on the GC B cells, we found that PCV2 infection activated the proliferation of dark zone GC B cells, but not the differentiation of light zone GC B cells. Furthermore, the transcriptional level of Prdm1 was not significantly altered by PCV2 infection, and the level of Bach2 was dramatically reduced. Further analysis showed that the interactions between light zone GC B cells and dendritic cells, macrophages, and follicular helper T cells were weakened in the spleens of PCV2-infected mice. In conclusion, this study found that PCV2 infection impairs the differentiation of B cells into functional memory B cells and plasma cells. This may be an important and previously unrecognized reason why PCV2 infection impairs vaccine efficiency. Full article

Streptococcus pneumoniae has been a PCV10 vaccine-preventable agent in Bulgaria since 2010. Our objective is to determine the phylogenetic structure of 170 invasive and non-invasive pneumococcal isolates, focusing on their serotypes and antimicrobial susceptibility. Serotyping was performed using latex agglutination, capsular swelling reaction, and serotype-specific PCRs. Antibiotic susceptibilities were assessed by broth microdilution. MLST was conducted to define the clonal composition. The non-PCV10 serotypes accounted for 88.2%. The predominant invasive pneumococcal disease (IPD) serotypes were 19A (39.3%), 19F (21.4%), 6C (10.7%), 7F (7.1%), and 3 (7.1%). The prevalent NIPD serotypes were 19A (18.3%), 6C (15.5%), 3 (10.6%), 15A (7.7%), and 6A (6.3%). The overall antimicrobial non-susceptibility rates were: benzylpenicillin (55.2%), ceftriaxone (15.2%), cefuroxime (35.8%), amoxicillin-clavulanic acid (38.8%), erythromycin (60.5%), clindamycin (57.0%), tetracycline (43.5%), trimethoprim-sulfamethoxazole (62.9%), and chloramphenicol (13.5%). The multidrug resistance (MDR) strains were 60.5%. The predominant clone CC320, represented 20.0% MDR 19A and 19F strains linked to Taiwan^19F-14 and GPSC1. CC273/Greece^6B-22 and CC386 accounted for 5.3% 6A and 6C isolates. Most serotype 3 isolates are associated with CC505, associated with Netherlands³-31 and GPSC12. Switching to a conjugate vaccine with broader serotype coverage could reduce the incidence of 19A, 6C, and 15A MDR S. pneumoniae clones in our country. Full article