Search Results (27)

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC. Full article

This article documents the first outbreak of aeromoniasis caused by Aeromonas veronii in farmed European seabass (Dicentrarchus labrax) along the Greek Ionian Sea coast. In late spring 2024, commercially sized fish exhibited anorexia, hemorrhages, and ulcers on the skin, accompanied by elevated morbidity and mortality rates. The outbreak spread rapidly across local farms in Sagiada Bay, reaching its peak in late summer, and extending into the Astakos Gulf, southern in the Ionian Sea. The postmortem examination revealed hemorrhages, organomegaly, abscess formation, and granulomatous inflammation. Aeromonas veronii was isolated from all examined individuals in nutrient media and confirmed by biochemical and molecular methods. Whole genome sequencing and phylogenetic analysis demonstrated genetic homogeneity among two strains from two different areas along the Ionian Sea and a close evolutionary relationship with other Aeromonas veronii strains from the Aegean Sea. Although genetically similar, the isolates exhibited differences in phenotypic and biochemical characteristics, indicating regional variability. The present study provides an overview of the pathology, clinical characteristics and progression of aeromoniasis in Ionian Sea aquaculture, highlighting the need for continued monitoring, in-depth genomic and phenotypic assessment, and the design of region-specific preventive strategies, including autogenous vaccines, for effective disease management. Full article

Antimicrobial resistance (AMR) is a major public health concern influenced by antimicrobial use (AMU) in animal production systems. In swine, metaphylactic treatments may contribute to the emergence and dissemination of resistance genes. In this study, we isolated bacteria from the nasal cavities of 50 sows across 10 farms in the Federal District, Brazil. A total of 132 bacterial isolates were obtained and tested for phenotypic resistance to 23 antimicrobials using the disk diffusion method. Resistance was detected against all tested antimicrobials, with an overall resistance rate of 55.6% (1605/2888 tests). The highest resistance rates were observed for bacitracin (92.4%) and penicillin (79.2%), while lower resistance rates were found for aminoglycosides. Most isolates exhibited multidrug resistance to 7–9 classes of antimicrobials, including strains of Staphylococcus, Escherichia coli, and Klebsiella—all of which are relevant in the context of One Health. Actinobacillus suis showed the highest resistance levels among all identified species. AMR was positively correlated with both the duration and the number of antimicrobial agents used in feed, reinforcing the need for prudent AMU practices. The use of autogenous vaccines against Pasteurella multocida was associated with reduced lung lesions, underscoring the value of vaccination in disease control. AMR surveillance programs may benefit from including bacterial colonizers from the microbiota, though further studies are necessary to better understand the resistance dynamics of these commensals. Full article

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article

Avian reoviruses (ARVs) represent a significant economic burden on the poultry industry due to their widespread prevalence and potential pathogenicity. These viruses, capable of infecting a diverse range of avian species, can lead to a variety of clinical manifestations, most notably tenosynovitis/arthritis. While many ARV strains are asymptomatic, pathogenic variants can cause severe inflammation and tissue damage in organs such as the tendons, heart, and liver. In broilers and turkeys, ARVs can induce severe arthritis/tenosynovitis, characterized by swollen hock joints and lesions in the gastrocnemius tendons. Additionally, ARVs have been implicated in other diseases, although their precise role in these conditions remains to be fully elucidated. In recent years, ARV cases have surged in the United States, emphasizing the need for effective control measures. Routine vaccination with commercial or autogenous vaccines is currently the primary strategy for mitigating ARV’s impact. Future research efforts should focus on enhancing our understanding of ARV-induced pathogenesis, identifying host factors that influence disease severity, and developing novel vaccines based on ongoing surveillance of circulating ARV strains. This review aims to explore the molecular aspects of ARV, including virus structure, replication, molecular epidemiology, the roles of its encoded proteins in host pathogenesis, and the immune response to ARV infection. Furthermore, we discuss the diagnostic approaches of avian reovirus and the potential biosecurity measures and vaccination trials in combating ARV and developing effective antiviral strategies. Full article

Background: Veterinary autogenous vaccines, similar to all injectable pharmaceutical products, must be tested to assess endotoxin concentrations. The Limulus Amebocyte Lysate Test (LAL test) is widely used in in vitro quality control assays for endotoxin detection, although it presents some ethical issues related to the production of reagents and is also characterized by a low specificity due to other contaminants that can activate the reaction. For all these reasons, a new recombinant factor C LAL test was developed. Aim: In this study, we described the comparison between two LAL test methods for in vitro quality control of veterinary autogenous vaccines, with the aim of evaluating the most suitable method and establishing an endotoxin concentration range for two different matrices. Methods: Two hundred batches of two different vaccine matrices were tested using the kinetic chromogenic LAL test and recombinant factor C endotoxin detection assay commercial kits. Results and Conclusions: Statistical analysis conducted after the validation of the recombinant factor C test exhibited a statistically significant correlation between the two methods and for both vaccine matrices, suggesting that the animal-free assay can be used as a routine quality control test for veterinary autogenous vaccines. Full article

The development of effective and innovative vaccination strategies is urgently needed to better control the spread and transmission of the low-pathogenic avian influenza H9N2 subtype (LPAI-H9N2) in poultry. In addition, the enhancement of innate immunity by some of these innovative inactivated vaccines has not yet been investigated. Here, an experiment was conducted in commercial broiler chickens to compare the immune response to two different inactivated H9N2 vaccines. For this, Group 1 (G1) broilers were vaccinated with vaccine 1 [Nobilis^® H9N2-P (pathogen-associated molecular patterns—PAMP) technology], broilers in G2 were vaccinated with vaccine 2 [an inactivated whole H9N2 virus (IWV) autogenous oil emulsion vaccine], while birds in G3 were not vaccinated. The study lasted 34 days. Innate immune parameters (phagocytic activity, nitric oxide, and lysozyme), cytokine signaling (IL-1β, IL-6, IL-8), humoral immunity using the hemagglutination inhibition (HI) test, and the gene expressions of IFN-γ and TLR-21 were assessed. The results showed a significant increase in innate immunity and modulatory cytokines at 24–48 h after the vaccination of G1 broilers, with a continuous increase until the end of the experiment. In addition, a significant increase in geometric mean HI titers was observed in G1 at 11 days post-vaccination (dpv), and a significant (p ˂ 0.05) upregulation of IFN-γ and TLR-21 was observed in the same group, G1, at 31 dpv compared to G2 and G3. Nobilis^® H9N2-P may induce faster and stronger innate and active humoral immunity compared to another IWV, which may contribute to the protection of broilers against early H9N2 infections. However, challenge protection studies for several IWV vaccines, including PAMP-H9N2 against LPAI-H9N2, should be further evaluated in both specific pathogen-free (SPF) and commercial broilers. Full article

Outbreaks of furunculosis cause significant losses in salmonid aquaculture worldwide. With a recent rise in antimicrobial resistance, regulatory measures to minimize the use of antibiotics in animal husbandry, including aquaculture, have increased scrutiny and availability of veterinary medical products to control this disease in production facilities. In such a regulatory environment, the utility of autogenous vaccines to assist with disease prevention and control as a veterinary-guided prophylactic measure is of high interest to the producers and veterinary services alike. However, evolving concepts of epidemiological units and epidemiological links need to be considered during approval and acceptance procedures for the application of autogenous vaccines in multiple aquaculture facilities. Here, we present the results of solid-state nanopore sequencing (Oxford Nanopore Technologies, ONT) performed on 54 isolates of Aeromonas salmonicida ssp. salmonicida sampled during clinical outbreaks of furunculosis in different aquaculture facilities from Bavaria, Germany, from 2017 to 2020. All of the performed analyses (phylogeny, single nucleotide polymorphism and 3D protein modeling for major immunogenic proteins) support a high probability that all studied isolates belong to the same epidemiological unit. Simultaneously, we describe a cost/effective method of whole genome analysis with the usage of ONT as a viable strategy to study outbreaks of other pathogens in the field of aquatic veterinary medicine for the purpose of developing the best autogenous vaccine candidates applicable to multiple aquaculture establishments. Full article

Vaccination strategies are used to manage Salmonella in chickens. Salmonella-killed vaccines are considered safer since they are inactivated. However, little is known regarding the cellular immune activities at the site of vaccine administration of Salmonella-killed vaccines. The growing feather (GF) cutaneous test has been shown to be an effective bioassay to monitor local tissue/cellular responses. We assessed local and systemic antibody responses initiated by intradermal injection of Salmonella-killed vaccines into GF-pulps of 14–15-week-old pullets. Treatments consisted of two autogenous Salmonella-killed vaccines (SV1 and SV2), S. Enteritidis (SE) lipopolysaccharide (SE-LPS), and the water-oil-water (WOW) emulsion vehicle. GF-pulps were collected before (0 h) and at 6, 24, 48, and 72 h post-GF-pulp injection for leukocyte population analysis, while heparinized blood samples were collected before (0 d) and at 3, 5, 7, 10, 14, 21, and 28 d after GF-pulp injections to assess plasma levels (a.u.) of SE-specific IgM, avian IgY (IgG), and IgA antibodies using an ELISA. Injection of GF-pulps with SV1, SV2, or SE-LPS, all in a WOW vehicle, initiated inflammatory responses characterized by the recruitment of heterophils, monocytes/macrophages, and a few lymphocytes. The WOW vehicle emulsion alone recruited more lymphocytes than vaccines or SE-LPS. The SV1 and SV2 vaccines stimulated Salmonella-specific IgM and IgA early, while IgG levels were greatly elevated later during the primary response. Overall, SV1 and SV2 stimulated a heterophil and macrophage-dominated local inflammatory- and SE-specific humoral response with an isotype switch from IgM to IgG, characteristic of a T-dependent primary antibody response. This study provides comprehensive information on innate and adaptive immune responses to autogenous Salmonella-killed vaccines and their components that will find application in the management of Salmonella in poultry. Full article

Vaccination is an essential method of immunological preventive care required for the health management of all animals, including fish. More particularly, immunization is necessary for in-land aquaculture to manage diseases in fish broodstocks and healthy seed production. According to the latest statistics in 2020, 90.3 million tons of capture fishery production was achieved from the aquaculture sector. Out of the above, 78.8 million tons were from marine water aquaculture sectors, and 11.5 million tons were from inland water aquaculture sectors. About a 4% decline in fish production was achieved in 2020 in comparison to 2018 from inland aquaculture sectors. On the other hand, the digestive protein content, healthy fats, and nutritional values of fish products are comparatively more affordable than in other meat sources. In 2014, about 10% of aquatic cultured animals were lost (costing global annual losses > USD 10 billion) due to infectious diseases. Therefore, vaccination in fish, especially in broodstocks, is one of the essential approaches to stop such losses in the aquaculture sector. Fish vaccines consist of whole-killed pathogens, protein subunits, recombinant proteins, DNA, or live-attenuated vaccines. Challenges persist in the adaption of vaccination in the aquaculture sector, the route of administration, the use of effective adjuvants, and, most importantly, the lack of effective results. The use of autogenous vaccines; vaccination via intramuscular, intraperitoneal, or oral routes; and, most importantly, adding vaccines in feed using top dressing methods or as a constituent in fish feed are now emerging. These methods will lower the risk of using antibiotics in cultured water by reducing environmental contamination. Full article

Studies that characterize bovine respiratory disease (BRD)-associated Pasteurella multocida isolates are scarce compared with research on isolates from other hosts and clinical backgrounds. In the present study, 170 P. multocida isolates from 125 BRD outbreaks were characterized by capsular and LPS typing as well as by virulotyping. Three capsular types (A, B, F) and three LPS genotypes (L2, L3, L6) were identified. Capsular and LPS typing revealed a very low genetic diversity (GD = 0.02) among P. multocida, with most isolates belonging to genotype A:L3 (97.6%). Virulotyping identified seven virulence-associated gene profiles, with two profiles including 95.9% of the isolates. A subset of isolates was further characterized by MLST and PFGE. The sequence types ST79 and ST13 were the most frequently identified and were grouped into the same clonal complex (CC13), a result that supports the clonal population structure of BRD-associated P. multocida isolates. PFGE typing also revealed a low genetic diversity (GD = 0.18), detecting a single pattern in 62.5% of the outbreaks in which multiple isolates were analyzed. Overall, 85.2% of the isolates belonged to pulsotypes with at least 80% genetic similarity, consistent with a clonal population structure observed by MLST analysis and corroborating the genetic relatedness of most P. multocida isolates associated with BRD in cattle. Full article

In Italy, dairy sheep farming represents a vital agro-industry sector, but it is still challenged by contagious agalactia (CA), which is endemic there, and vaccination is the most economical and sustainable tool for control. This study aimed to evaluate the combined Mycoplasma agalactiae (Ma)-Staphylococcus aureus (Sa) vaccine (Ma–Sa) against the Ma monovalent vaccine in ewes. Twelve primiparous Ma-free ewes were randomly grouped into three equal groups: first, the control group injected with placebo, second, the group vaccinated with the Ma monovalent vaccine, and third, the group vaccinated with Ma–Sa combined vaccine, with two S/C doses at 45-day intervals. The animals were examined for serological, hematological, and somatic cell count (SCC) changes for 17 successive weeks. A significant increase in anti-Ma antibody mean titers, leukocytes, and platelets was observed in the vaccinated animals, with the highest values in those who received the combined vaccine. Neutrophils were high only in the animals who received the combined vaccine. SCC was lower in the vaccinated animals during the first six weeks. This study concludes that the combined Ma–Sa vaccines enhance immune response and potentiate its efficacy against Ma. This improvement might be attributed to the sensitization/activation effect of S. aureus on platelets, which are recoded to act as a key regulator for the coordination of all components of the innate immune system. Even though this study included a small number of animals, its findings about the potentialities of this inactivated vaccine in the control of CA are strongly encouraging. Further confirmation might be needed through additional replicates and a challenge study is needed before proceeding with widespread use. Full article

Escherichia coli (E. coli) is one of the most common bacterial causes of infection in poultry farming. Whether the infection is localized or systemic, a primary or secondary disease, it is most frequently treated through the application of wide-spectrum antimicrobials. Excessive use of antimicrobials in agriculture is significantly contributing to the worldwide rise of antimicrobial resistance, but is also very expensive and often ineffective in the long term. Here, we present a case where a colibacillosis outbreak on a family farm of laying hens was treated using an autogenous vaccine. The birds had septicemia, cellulitis, and severe skin wounds. They were not vaccinated against E. coli, and did not receive any antimicrobials previously. E. coli strains were isolated from the daily mortalities on the farm and used for preparation of the vaccine. Each bird was given an intramuscular injection of the autogenous vaccine. The immunogenicity of the vaccine was tested by the determination of specific antibody levels in the sera of the birds using the in-house ELISA. Shortly after vaccination, the morbidity and mortality rates significantly decreased, and egg production was improved. The application of the autogenous vaccine served as a curative and preventive measure, and has proven to be a very efficient method of antimicrobial therapy. Full article

A randomized control trial was performed over a five-year period to assess the efficacy and antibody response induced by autogenous and commercial vaccine formulations against infectious bovine keratoconjunctivitis (IBK). Calves were randomly assigned each year to one of three arms: an autogenous vaccine treatment that included Moraxella bovis (M. bovis), Moraxella bovoculi, and Mycoplasma bovoculi antigens, a commercial M. bovis vaccine treatment, or a sham vaccine treatment that consisted only of adjuvant. A total of 1198 calves were enrolled in the study. Calves were administered the respective vaccines approximately 21 days apart, just prior to turnout on summer pastures. Treatment effects were analyzed for IBK incidence, retreatment incidence, 205-day adjusted weaning weights, and antibody response to the type IV pilus protein (pili) of M. bovis as measured by a novel indirect enzyme-linked immunosorbent screening assay (ELISA). Calves vaccinated with the autogenous formulation experienced a decreased cumulative incidence of IBK over the entire study compared to those vaccinated with the commercial and sham formulations (24.5% vs. 30.06% vs. 30.3%, respectively, p = 0.25), and had less IBK cases that required retreatment compared to the commercial and sham formulations (21.4% vs. 27.9% vs. 34.3%, respectively, p = 0.15), but these differences were not significant. The autogenous formulation induced a significantly stronger antibody response than the commercial (p = 0.022) and sham formulations (p = 0.001), but antibody levels were not significantly correlated with IBK protection (p = 0.37). Full article

Escherichia coli is the main bacterial cause of major economic losses and animal welfare issues in poultry production. In this study, we investigate the effect of an autogenous vaccine on E. coli strains longitudinally isolated from broiler breeder flocks on two farms. In total, 115 E. coli isolates were sequenced using Illumina technologies, and compared based on a single-nucleotide polymorphism (SNP) analysis of the core-genome and antimicrobial resistance (AMR) genes they carried. The results showed that SNP-based phylogeny corresponds to a previous multilocus-sequence typing (MLST)-based phylogeny. Highly virulent sequence types (STs), including ST117-F, ST95-B2, ST131-B2 and ST390-B2, showed a higher level of homogeneity. On the other hand, less frequent STs, such as ST1485, ST3232, ST7013 and ST8573, were phylogenetically more distant and carried a higher number of antimicrobial resistance genes in most cases. In total, 25 antimicrobial genes were detected, of which the most prevalent were mdf(A) (100%), sitABCD (71.3%) and tet(A) (13.91%). The frequency of AMR genes showed a decreasing trend over time in both farms. The highest prevalence was detected in strains belonging to the B1 phylogenetic group, confirming the previous notion that commensal strains act as reservoirs and carry more resistance genes than pathogenic strains that are mostly associated with virulence genes. Full article