A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists.

Nanovaccines have significantly contributed in the prevention and treatment of diseases. However, most of these technologies rely on chemical or hybrid semibiological synthesis methods, which limit the manufacturing performance advantages and improved inoculation outcomes compared with traditional vaccines. Herein, a universal and purely biological nanovaccine system is reported.

Vaccines to Control in Poultry.

This review is focused on describing and analyzing means by which serotype strains have been genetically modified with the purpose of developing safe, efficacious vaccines to present -induced disease in poultry and to prevent colonization of poultry to reduce transmission through the food chain in and on eggs and poultry meat. Emphasis is on use of recently developed means to generate defined deletion mutations to eliminate genetic sequences conferring antimicrobial resistance or residual elements that might lead to genetic instability. Problems associated with prior means to develop vaccines are discussed with presentation of various means by which these problems have been lessened, if not eliminated.

Vaccine Candidate Delivering Infectious Bronchitis Virus S1 Protein to Induce Protection.

Infectious bronchitis (IB) is a highly infectious viral disease of chickens which causes significant economic losses in the poultry industry worldwide. An effective vaccine against IB is urgently needed to provide both biosafety and high-efficiency immune protection. In this study, the S1 protein of the infectious bronchitis virus was delivered by a recombinant attenuated vector to form the vaccine candidate χ11246(pYA4545-S1).

A bacterial vesicle-based pneumococcal vaccine against influenza-mediated secondary Streptococcus pneumoniae pulmonary infection.

Streptococcus pneumoniae (Spn) is a common pathogen causing a secondary bacterial infection following influenza, which leads to severe morbidity and mortality during seasonal and pandemic influenza. Therefore, there is an urgent need to develop bacterial vaccines that prevent severe post-influenza bacterial pneumonia. Here, an improved Yersinia pseudotuberculosis strain (designated as YptbS46) possessing an Asd plasmid pSMV92 could synthesize high amounts of the Spn pneumococcal surface protein A (PspA) antigen and monophosphoryl lipid A as an adjuvant.

A Bacterial mRNA-Lysis-Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery.

Engineered vector-based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge.

Recombinant Attenuated Vaccine Displaying Regulated Lysis to Confer Biological Containment and Protect Catfish against Edwardsiellosis.

We implemented a unique strategy to construct a recombinant attenuated vaccine (RAEV) with a biological containment phenotype that causes regulated bacterial cell wall lysis. This process ensures that the vaccine strain is not able to persist in the environment. The gene is responsible for the catalysis of one of the first steps in the biosynthesis of muramic acid, which is a crucial component of the bacterial cell wall.

Estimating plume reach and trapping radii for male and female Cydia pomonella (Lepidoptera: Tortricidae) captured in pheromone-kairomone baited traps in Washington State apple orchards under mating disruption.

Male Cydia pomonella (L.) (Lepidoptera: Tortricidae) dispersion has largely been studied in nonmating disrupted orchards due to synthetic pheromone interference with capture in monitoring traps. Little is known about female dispersion.

Neuronopathic GBA1L444P Mutation Accelerates Glucosylsphingosine Levels and Formation of Hippocampal Alpha-Synuclein Inclusions.

The most common genetic risk factor for Parkinson's disease (PD) is heterozygous mutations , which encodes for the lysosomal enzyme, glucocerebrosidase. Reduced glucocerebrosidase activity associates with an accumulation of abnormal α-synuclein (α-syn) called Lewy pathology, which characterizes PD. PD patients heterozygous for the neuronotypic GBA1L444P mutation (GBA1) have a 5.

Protective immunity enhanced vaccine vectors delivering antigens reduce stomach colonization in mice.

is a major cause of gastric mucosal inflammation, peptic ulcers, and gastric cancer. Emerging antimicrobial-resistant has hampered the effective eradication of frequent chronic infections. Moreover, a safe vaccine is highly demanded due to the absence of effective vaccines against .

Role of RpoS in Regulating Stationary Phase Salmonella Typhimurium Pathogenesis-Related Stress Responses under Physiological Low Fluid Shear Force Conditions.

The discovery that biomechanical forces regulate microbial virulence was established with the finding that physiological low fluid shear (LFS) forces altered gene expression, stress responses, and virulence of the enteric pathogen Salmonella enterica serovar Typhimurium during the log phase. These log phase LFS-induced phenotypes were independent of the master stress response regulator, RpoS (σ). Given the central importance of RpoS in regulating stationary-phase stress responses of S.

Group 3 innate lymphoid cell pyroptosis represents a host defence mechanism against Salmonella infection.

Group 3 innate lymphoid cells (ILC3s) produce interleukin (IL)-22 and coordinate with other cells in the gut to mount productive host immunity against bacterial infection. However, the role of ILC3s in Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, which causes foodborne enteritis in humans, remains elusive.

Remodeling to generate a highly immunogenic outer membrane vesicle vaccine against pneumonic plague.

Significance, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. This plague bacillus has been used as a biological weapon during human history and is currently one of the deadliest biological threats. Currently, no licensed plague vaccines are available in the Western world.

Construction and Evaluation of Recombinant Attenuated Vaccine (RAEV) Vector System Encoding (Ich) Antigen IAG52B.

We have successfully designed and constructed a RAEV vector system with regulated-delayed attenuation attributes that synthesizes (Ich) protective antigen IAG52B to enable vaccination of fish susceptible to edwardsiellosis and white spot disease. The first feature of this vaccine delivery system is an strain carrying genomic deletions of . AsdA is an enzyme necessary for the synthesis of diaminopimelic acid (DAP), which is an essential component of the peptidoglycan layer of the cell wall of Gram-negative bacteria.

A triple-sugar regulated Salmonella vaccine protects against Clostridium perfringens-induced necrotic enteritis in broiler chickens.

Gram-positive Clostridium perfringens type G, the causative agent of necrotic enteritis (NE), has gained more attention in the poultry industry due to governmental restrictions on the use of growth-promoting antibiotics in poultry feed. Our previous work has proved that regulated delayed lysis Salmonella vaccines delivering a plasmid encoding an operon fusion of the nontoxic C-terminal adhesive part of alpha toxin and a GST-NetB toxin fusion were able to elicit significant protective immunity in broilers against C. perfringens challenge.

Virulence, immunogenicity and live vaccine potential of aroA and phoP mutants of Edwardsiella piscicida in zebrafish.

Vaccination remains the most effective approach for prevention and control of infectious diseases in aquaculture. Edwardsiella piscicida is a causative agent of edwardsiellosis leading to mass mortality in a variety of fish species, leading to huge economic losses in the aquaculture industry. In this study, we have deleted the aroA and phoP genes in E.

Characterization of Brucella abortus S19 as a challenge strain for use in a mouse model of brucellosis.

The objective of this project was to conduct a feasibility study to determine whether the Brucella abortus S19 vaccine infects and persists in mice and determine whether S19 can be used as a challenge strain for vaccine trial studies. Groups of BALB/c mice were inoculated (intraperitoneally, subcutaneously, intranasally) and euthanized to determine colonization titers in the spleens and lungs. This study showed that S19 does infect and persist in the tissues of mice for 8 weeks and demonstrates that S19 can be used, safely and economically under BSL2 containment, as the challenge strain for future trials to evaluate vaccine efficacy.

Pathogenicity and immunogenicity of Edwardsiella piscicida ferric uptake regulator (fur) mutations in zebrafish.

Edwardsiella piscicida is the etiological agent of edwardsiellosis in fish and causes severe economic losses in global aquaculture. Vaccination would be the most effective method to prevent infectious diseases and their associated economic losses. The ferric uptake regulator (Fur) is an important transcriptional global regulator of Gram-negative bacteria.

Mucosal Delivery of a Self-destructing Salmonella-Based Vaccine Inducing Immunity Against Eimeria.

A programmed self-destructive Salmonella vaccine delivery system was developed to facilitate efficient colonization in host tissues that allows release of the bacterial cell contents after lysis to stimulate mucosal, systemic, and cellular immunities against a diversity of pathogens. Adoption and modification of these technological improvements could form part of an integrated strategy for cost-effective control and prevention of infectious diseases, including those caused by parasitic pathogens. Avian coccidiosis is a common poultry disease caused by Eimeria.

Differentially regulated promoters for antigen expression in Salmonella vaccine strains.

In most attenuated Salmonella enterica vaccines, heterologous antigens are expressed under the control of strong inducible promoters to ensure a high level of synthesis. Although high expression levels of the antigen can improve the immunogenicity of the vaccine, they might be toxic to the Salmonella carrier. Expression problems could be avoided by the use of promoters with specific characteristics with respect to strength and timing of expression.

Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity.

There is the notion that infection with a virulent intestinal pathogen induces generally stronger mucosal adaptive immunity than the exposure to an avirulent strain. Whether the associated mucosal inflammation is important or redundant for effective induction of immunity is, however, still unclear. Here we use a model of auxotrophic Salmonella infection in germ-free mice to show that live bacterial virulence factor-driven immunogenicity can be uncoupled from inflammatory pathogenicity.

Attenuated Typhimurium expressing Paratyphoid A O-antigen induces protective immune responses against two strains.

serovar Paratyphi A is the main causative agent of paratyphoid fever in many Asian countries. As paratyphoid is spread by the fecal-oral route, the most effective means of controlling . Paratyphi A infection is through the availability of clean water supplies and working sanitation services.

Regulating vitamin B12 biosynthesis via the Cbl riboswitch in strain UF1.

Vitamin B12 (VB12) is a critical micronutrient that controls DNA metabolic pathways to maintain the host genomic stability and tissue homeostasis. We recently reported that the newly discovered commensal , P. UF1, regulates the intestinal immunity to resist pathogen infection, which may be attributed in part to VB12 produced by this bacterium.

A Recombinant Attenuated Vaccine Delivering a YopE-LcrV Fusion Elicits Broad Protection against Plague and Yersiniosis in Mice.

In this study, a novel recombinant attenuated PB1+ strain (χ10069) engineered with Δ Δ Δ triple mutations was used to deliver a fusion protein, YopE amino acid 1 to 138-LcrV (YopE-LcrV), to Swiss Webster mice as a protective antigen against infections by yersiniae. χ10069 bacteria harboring the pYA5199 plasmid constitutively synthesized the YopE-LcrV fusion protein and secreted it via the type 3 secretion system (T3SS) at 37°C under calcium-deprived conditions. The attenuated strain χ10069(pYA5199) was manifested by the establishment of controlled infection in different tissues without developing conspicuous signs of disease in histopathological analysis of microtome sections.