Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity.

A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo.

Evaluation of Efficacy of Surface Coated versus Encapsulated Influenza Antigens in Mannose-Chitosan Nanoparticle-Based Intranasal Vaccine in Swine.

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination.

Heritability and genome-wide association study of vaccine-induced immune response in Beagles: A pilot study.

Both genetic and non-genetic factors contribute to individual variation in the immune response to vaccination. Understanding how genetic background influences variation in both magnitude and persistence of vaccine-induced immunity is vital for improving vaccine development and identifying possible causes of vaccine failure. Dogs provide a relevant biomedical model for investigating mammalian vaccine genetics; canine breed structure and long linkage disequilibrium simplify genetic studies in this species compared to humans.

Characterization of the Efficacy of a Split Swine Influenza A Virus Nasal Vaccine Formulated with a Nanoparticle/STING Agonist Combination Adjuvant in Conventional Pigs.

Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Intranasal (IN) vaccination has the potential to reduce flu infection. We investigated the efficacy of split SwIAV H1N2 antigens adsorbed with a plant origin nanoparticle adjuvant [Nano11-SwIAV] or in combination with a STING agonist ADU-S100 [NanoS100-SwIAV].

Intradermal Vaccination against Influenza with a STING-Targeted Nanoparticle Combination Adjuvant Induces Superior Cross-Protective Humoral Immunity in Swine Compared with Intranasal and Intramuscular Immunization.

The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV), a potential pandemic-causing agent, continues to be an urgent global health concern. Commercially available vaccines provide suboptimal cross-protection against circulating subtypes of swIAV, which can lead to worldwide economic losses and poor zoonosis deterrence. The limited efficacy of current swIAV vaccines demands innovative strategies for the development of next-generation vaccines.

Aluminum Adjuvants-'Back to the Future'.

Aluminum-based adjuvants will continue to be a key component of currently approved and next generation vaccines, including important combination vaccines. The widespread use of aluminum adjuvants is due to their excellent safety profile, which has been established through the use of hundreds of millions of doses in humans over many years. In addition, they are inexpensive, readily available, and are well known and generally accepted by regulatory agencies.

Intestinal colonization with and mucosal immune response in mice treated with cefoperazone oral antibiotic.

, an emerging multi-drug resistant fungal pathogen, causes invasive infections in humans. The factors regulating the colonization of in host niches are not well understood. In this study, we examined the effect of antibiotic-induced gut dysbiosis on intestinal colonization, dissemination, microbiome composition and the mucosal immune response.

Proteomic analysis of canine vaccines.

Objective: To use proteomic analysis to identify qualitatively and quantitatively mammalian protein components of commercial veterinary vaccines against canine distemper, leptospirosis, borreliosis, and rabies.

Sample: 25 licensed veterinary vaccines (from 4 different manufacturers) against canine distemper and leptospirosis, borreliosis, and rabies (3-year and 1-year durations of immunity).

Procedures: Duplicate samples from a single-lot vial of each vaccine were prepared by acetone precipitation and proteolysis with trypsin and Lys-C protease mix.

Effect of different adjuvant formulations on the antibody response of horses to porcine zona pellucida proteins.

Immunization with porcine zona pellucida (PZP) proteins is being used successfully to induce infertility in wildlife including horses. However, widespread adoption of this method to control the growth of horse populations requires further refinement in order to induce long-term infertility, reduce the frequency and severity of injection site reactions, and make the vaccines easier to administer. The next generation of PZP-based vaccines will likely be a controlled-release formulation with different adjuvants from the Freund's adjuvants used in existing vaccines.

Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant.

Recent studies have shown that corn-derived cationic α-D-glucan nanoparticles, known as Nano-11, significantly increase the immune response when used as a vaccine adjuvant in mice and in pigs. Furthermore, the nanoparticles can be formulated with other immunostimulators such as poly(I:C), which further enhances the immune response. The current experiments were aimed at elucidating the mechanism of action of Nano-11 alone and in combination with poly(I:C).

Alpha-D-glucan-based vaccine adjuvants: Current status and future perspectives.

Nanoparticles (NPs) are increasingly used as efficient vaccine antigen-delivery platforms and vaccine adjuvants. Alpha (α)-D-glucans are polysaccharide polymers found in plants, animals, and microbes. Phytoglycogen (PG) is a densely branched dendrimer-like α-D-glucan that forms nanoparticle structures.

Effect of medium-chain fatty acids on growth, health, and immune response of dairy calves.

It is necessary for the dairy industry to reduce calf morbidity and mortality, and the reliance on antibiotics to treat sick calves, to address the growing concern regarding antibiotic resistant bacteria. The primary objective of this study was to evaluate the effect that feeding dairy calves medium-chain fatty acids (MCFA) has on growth performance and health, and the secondary objective was to evaluate the effect of MCFA on energy status around weaning and the adaptive immune response following a vaccine challenge. Thirty-three Holstein bull calves (5 ± 1.

Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control in the Intestine.

Invasive () infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings from our lab indicate that taurocholic acid (), a major bile acid present in the intestine, promotes CA colonization and dissemination.

Bile Acid Regulates the Colonization and Dissemination of from the Gastrointestinal Tract by Controlling Host Defense System and Microbiota.

(CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of taurocholic acid (TCA), a major bile acid in antibiotic-treated mice susceptible to CA infection.

Local and Systemic Changes in Lipid Profile as Potential Biomarkers for Canine Atopic Dermatitis.

Lipids play a critical role in the skin as components of the epidermal barrier and as signaling and antimicrobial molecules. Atopic dermatitis in dogs is associated with changes in the lipid composition of the skin, but whether these precede or follow the onset of dermatitis is unclear. We applied rapid lipid-profiling mass spectrometry to skin and blood of 30 control and 30 atopic dogs.

Intranasal Delivery of Inactivated Influenza Virus and Poly(I:C) Adsorbed Corn-Based Nanoparticle Vaccine Elicited Robust Antigen-Specific Cell-Mediated Immune Responses in Maternal Antibody Positive Nursery Pigs.

We designed the killed swine influenza A virus (SwIAV) H1N2 antigen (KAg) with polyriboinosinic:polyribocytidylic acid [(Poly(I:C)] adsorbed corn-derived Nano-11 particle based nanovaccine called Nano-11-KAg+Poly(I:C), and evaluated its immune correlates in maternally derived antibody (MDA)-positive pigs against a heterologous H1N1 SwIAV infection. Immunologically, in tracheobronchial lymph nodes (TBLN) detected enhanced H1N2-specific cytotoxic T-lymphocytes (CTLs) in Nano-11-KAg+Poly(I:C) vaccinates, and in commercial vaccinates detected CTLs with mainly IL-17A and early effector phenotypes specific to both H1N2 and H1N1 SwAIV. In commercial vaccinates, activated H1N2- and H1N1-specific IFNγ&TNFα, IL-17A and central memory T-helper/Memory cells, and in Nano-11-KAg+Poly(I:C) vaccinates H1N2-specific central memory, IFNγ and IFNγ&TNFα, and H1N1-specific IL-17A T-helper/Memory cells were observed.

Effective and Safe Stimulation of Humoral and Cell-Mediated Immunity by Intradermal Immunization with a Cyclic Dinucleotide/Nanoparticle Combination Adjuvant.

Intradermal (ID) immunization is an attractive route of vaccination because it targets tissue rich in dendritic cells, has dose-sparing potential, and allows needle-free delivery. However, few adjuvants are effective, nonreactogenic, and compatible with needle-free delivery devices. In this study, we demonstrate that a combination adjuvant composed of cyclic-di-AMP (cdAMP) and the plant-derived nanoparticle adjuvant Nano-11 significantly enhanced the immune response to ID-injected vaccines in mice and pigs with minimal local reaction at the injection site.

Development of IglC and GroEL recombinant vaccines for francisellosis in Nile tilapia, Oreochromis niloticus.

Warm-water piscine francisellosis is a granulomatous bacterial disease caused by Francisella orientalis (Fo). The disease has been detected in a wide range of fish species globally, causing mortalities as high as 90% and significant economic losses. Currently there are no commercially available vaccines and few treatment options exist.

Lipidomic Profiling of the Epidermis in a Mouse Model of Dermatitis Reveals Sexual Dimorphism and Changes in Lipid Composition before the Onset of Clinical Disease.

Atopic dermatitis (AD) is a multifactorial disease associated with alterations in lipid composition and organization in the epidermis. Multiple variants of AD exist with different outcomes in response to therapies. The evaluation of disease progression and response to treatment are observational assessments with poor inter-observer agreement highlighting the need for molecular markers.

Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice.

A Nanoparticle-Poly(I:C) Combination Adjuvant Enhances the Breadth of the Immune Response to Inactivated Influenza Virus Vaccine in Pigs.

Intranasal vaccination elicits secretory IgA (SIgA) antibodies in the airways, which is required for cross-protection against influenza. To enhance the breadth of immunity induced by a killed swine influenza virus antigen (KAg) or conserved T cell and B cell peptides, we adsorbed the antigens together with the TLR3 agonist poly(I:C) electrostatically onto cationic alpha-D-glucan nanoparticles (Nano-11) resulting in Nano-11-KAg-poly(I:C) and Nano-11-peptides-poly(I:C) vaccines. In vitro, increased TNF-α and IL-1ß cytokine mRNA expression was observed in Nano-11-KAg-poly(I:C)-treated porcine monocyte-derived dendritic cells.

Genetic Variation in the Magnitude and Longevity of the IgG Subclass Response to a Diphtheria-Tetanus-Acellular Pertussis (DTaP) Vaccine in Mice.

The type of IgG subclasses induced by vaccination is an important determinant of vaccine efficacy because the IgG subclasses vary in their biological function. The goal of this study was to determine the influence of the genetic background on the production and duration of vaccine-induced IgG subclasses. IgG1, IgG2b, and IgG3 titers against diphtheria toxoid (DT), pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn) were measured in mice from 28 different inbred and wild-derived strains vaccinated with an aluminum hydroxide-adjuvanted DTaP vaccine.

Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I:C) and CpG enhances the magnitude and avidity of the humoral immune response.

Subunit vaccines generally require adjuvants to achieve optimal immune responses. Toll-like receptor (TLR) agonists are promising immune potentiators, but rapid diffusion from the injection site reduces their local effective concentration and may cause systemic reactions. In this study, we investigated the potential of aluminum hydroxide adjuvant (AH) to adsorb the TLR3 agonist poly(I:C) and TLR9 agonist CpG and compared the effect of the combination adjuvant on the immune response with either the TLR agonists or AH alone in mice.