Protection of Broiler Chickens Against Necrotic Enteritis by Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine Exploiting the Gut-Lung-Axis Concept.

(CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge.

Induction of trained immunity in broiler chickens following delivery of oligodeoxynucleotide containing CpG motifs to protect against Escherichia coli septicemia.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) can promote antimicrobial immunity in chickens by enriching immune compartments and activating immune cells. Innate memory, or trained immunity, has been demonstrated in humans and mice, featuring the absence of specificity to the initial stimulus and subsequently cross-protection against pathogens. We hypothesize that CpG-ODN can induce trained immunity in chickens.

Oligodeoxynucleotides containing CpG motifs upregulate bactericidal activities of heterophils and enhance immunoprotection of neonatal broiler chickens against Salmonella Typhimurium septicemia.

In the past, we demonstrated that oligodeoxynucleotides containing CpG motifs (CpG-ODN) mimicking bacterial DNA, stimulate the innate immune system of neonatal broiler chickens and protect them against Escherichia coli and Salmonella Typhimurium (S. Typhimurium) septicemia. The first line of innate immune defense mechanism is formed by heterophils and plays a critical protective role against bacterial septicemia in avian species.

A Marek's Disease Virus Messenger RNA-Based Vaccine Modulates Local and Systemic Immune Responses in Chickens.

Marek's disease (MD), caused by the Marek's disease virus, is a lymphoproliferative disease in chickens that can be controlled by vaccination. However, the current vaccines can limit tumor growth and death but not virus replication and transmission. The present study aimed to evaluate host responses following intramuscular injection of an mRNA vaccine encoding gB and pp38 proteins of the MDV within the first 36 h.

Efficacy of an inactivated influenza vaccine adjuvanted with Toll-like receptor ligands against transmission of H9N2 avian influenza virus in chickens.

Avian influenza viruses (AIV), including the H9N2 subtype, pose a major threat to the poultry industry as well as to human health. Although vaccination provides a protective control measure, its effect on transmission remains uncertain in chickens. The objective of the present study was to investigate the efficacy of beta-propiolactone (BPL) whole inactivated H9N2 virus (WIV) vaccine either alone or in combination with CpG ODN 2007 (CpG), poly(I:C) or AddaVax™ (ADD) to prevent H9N2 AIV transmission in chickens.

Efficacy and tolerability of an mRNA vaccine expressing gB and pp38 antigens of Marek's disease virus in chickens.

Marek's disease is a contagious proliferative disease of chickens caused by an alphaherpesvirus called Marek's disease virus. A bivalent mRNA vaccine encoding MDV's glycoprotein-B and phosphoprotein-38 antigens was synthesized and encapsulated in lipid nanoparticles. Tumor incidence, lesion score, organ weight indices, MDV genome load and cytokine expression were used to evaluate protection and immunostimulatory effects of the tested mRNA vaccine after two challenge trials.

In ovo administration of retinoic acid enhances cell-mediated immune responses against an inactivated H9N2 avian influenza virus vaccine.

The H9N2 subtype avian influenza virus (AIV) is a low pathogenic AIV that infects avian species and lead to huge economical losses in the poultry industry. The unique immunomodulatory properties of Retinoic acid (RA), an active component of vitamin A, highlights its potential to enhance chicken's resistance to infectious diseases and perhaps vaccine-induced immunity. Therefore, the present study evaluated the effects of in ovo supplementation of RA on the immunogenicity and protective efficacy of an inactivated avian influenza virus vaccine.

The tumor microenvironment generated by Marek's disease virus suppresses interferon-gamma-producing gamma delta T cells.

The tumor microenvironment (TME) is generated by the cross-talk among tumor cells, immune system cells, and stromal cells. The TME generated by Marek's disease virus (MDV) is suggested to display an immunosuppressive milieu due to immune inhibitory molecules and cytokines which are possibly induced by MDV-transformed cells and regulatory T cells. Both anti-tumor and pro-tumor gamma delta (γδ) T cells are reported in human cancer.

Effect of Pre-Treatment with a Recombinant Chicken Interleukin-17A on Vaccine Induced Immunity against a Very Virulent Marek's Disease Virus.

The host response to pathogenic microbes can lead to expression of interleukin (IL)-17, which has antimicrobial and anti-viral activity. However, relatively little is known about the basic biological role of chicken IL-17A against avian viruses, particularly against Marek's disease virus (MDV). We demonstrate that, following MDV infection, upregulation of IL-17A mRNA and an increase in the frequency of IL-17A+ T cells in the spleen occur compared to control chickens.

Treatment with Toll-like Receptor (TLR) Ligands 3 and 21 Prevents Fecal Contact Transmission of Low Pathogenic H9N2 Avian Influenza Virus (AIV) in Chickens.

Transmission of H9N2 avian influenza virus (AIV) can occur in poultry by direct or indirect contact with infected individuals, aerosols, large droplets and fomites. The current study investigated the potential of H9N2 AIV transmission in chickens via a fecal route. Transmission was monitored by exposing naïve chickens to fecal material from H9N2 AIV-infected chickens (model A) and experimentally spiked feces (model B).

Differential activation of chicken gamma delta T cells from different tissues by Toll-like receptor 3 or 21 ligands.

Gamma delta (γδ) T cells are highly enriched in mucosal barrier sites including intestinal tissues where microbial infections and tumors often originate in mammals. Human γδ T cells recognize stress antigens and microbial signals via their T cell receptor (TCR), natural killer (NK) receptors, and pattern recognition receptors. However, little is known about antigens or ligands capable of stimulating chicken γδ T cells.

The severe acute respiratory syndrome coronavirus 2 non-structural proteins 1 and 15 proteins mediate antiviral immune evasion.

Infection with pathogenic viruses is often sensed by innate receptors such as Toll-Like Receptors (TLRs) which stimulate type I and III interferons (IFNs) responses, to generate an antiviral state within many cell types. To counteract these antiviral systems, many viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), encode non-structural proteins (NSPs) that mediate immune evasion. Using an overexpression system in A549 ​cells, we demonstrated a significant increase ( ​≤ ​0.

Phenotypic characterization of gamma delta (γδ) T cells in chickens infected with or vaccinated against Marek's disease virus.

Marek's disease (MD) vaccines reduce the incidence of MD but cannot control virus shedding. To develop new vaccines, it is essential to elucidate mechanisms of immunity to Marek's disease virus (MDV) infection. In this regard, gamma delta (γδ) T cells may play a significant role in prevention of viral spread and tumor surveillance.

The Regulatory Microenvironment in Feathers of Chickens Infected with Very Virulent Marek's Disease Virus.

Vaccines against Marek's disease can protect chickens against clinical disease; however, infected chickens continue to propagate the Marek's disease virus (MDV) in feather follicles and can shed the virus into the environment. Therefore, the present study investigated if MDV could induce an immunoregulatory microenvironment in feathers of chickens and whether vaccines can overcome the immune evasive mechanisms of MDV. The results showed an abundance of CD4CD25 and CD4 transforming growth factor-beta (TGF-β) T regulatory cells in the feathers of MDV-infected chickens at 21 days post-infection.

Effects of administration of probiotic lactobacilli on immunity conferred by the herpesvirus of turkeys vaccine against challenge with a very virulent Marek's disease virus in chickens.

Several vaccines have been used to control Marek's disease (MD) in chickens. However, the emergence of new strains of Marek's disease virus (MDV) imposes a threat to vaccine efficacy. Therefore, the current study was carried out to investigate whether concurrent administration of probiotics with the herpesvirus of turkeys (HVT) vaccine enhances its protective efficacy against MDV infection.

Gut microbiota is associated with protection against Marek's disease virus infection in chickens.

Marek's Disease Virus (MDV) infects chickens via respiratory route and causes lymphomas in internal organs including gastrointestinal tract. MDV infection causes a shift in the gut microbiota composition. However, interactions between the gut microbiota and immune responses against MDV infection are not well understood.

Characterization of innate responses induced by in ovo administration of encapsulated and free forms of ligands of Toll-like receptor 4 and 21 in chicken embryos.

Toll-like receptors (TLRs) are a family of innate receptors that recognize pathogen-associated molecular patterns, including double-stranded RNA, CpG DNA and lipopolysaccharide (LPS). After interaction with their ligands, TLRs initiate innate responses that are manifested by activating cells and inducing expression of cytokines that help mediate adaptive immune responses. TLR ligands (TLR-Ls) have the potential to be used prophylactically (alone) or as vaccine adjuvants to promote host immunity.

Isolation and purification of Gallid herpesvirus 2 strains currently distributed in Japan.

Gallid herpesvirus 2 (GaHV-2) causes malignant lymphomas in chickens (Marek's disease, MD). Although MD is controlled through vaccination efforts, field isolates of GaHV-2 have increased in virulence worldwide and even cause MD in vaccinated chickens. GaHV-2 strains are classified into four categories (mild, virulent, very virulent and very virulent +) based on the virulence exhibited in experimental infection in unvaccinated or MD-vaccinated susceptible chickens.

Expression analysis of programmed death ligand 2 in tumors caused by the avian oncovirus Marek's disease virus.

PD-L2 is a ligand of the immunoinhibitory receptor PD-1. Here, we report functional and expression analyses of PD-L2 in tumor lesions and spleens from chickens infected with gallid herpesvirus 2 (GaHV-2, Marek's disease virus), which induces malignant lymphomas in chickens. We show that the expression of IFN-γ protein was decreased in PBMCs and splenocytes co-cultured with PD-L2-expressing cells and that the expression of PD-L2 mRNA was significantly higher in the spleens of infected chickens in the latent phase and in tumor lesions caused by GaHV-2.

Characterization of Meq proteins from field isolates of Marek's disease virus in Japan.

Serotype 1 strains of Marek's disease virus (MDV-1) cause malignant lymphomas in chickens (Marek's disease; MD). Although MD has been controlled by vaccination, field isolates of MDV-1 have tended to increase in virulence and cause MD even in vaccinated chickens. Meq, a putative MDV-1 oncoprotein, resembles the Jun/Fos family of basic leucine zipper (bZIP) transcription factors and can regulate the expression of viral and cellular genes as a homodimer or as a heterodimer with a variety of bZIP family proteins.

Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus.

Background: An immunoinhibitory receptor, programmed death-1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion mechanisms for several pathogens causing chronic infections and for neoplastic diseases. However, little has been reported for the functions of these molecules in chickens. Thus, in this study, their expressions and roles were analyzed in chickens infected with Marek's disease virus (MDV), which induces immunosuppression in infected chickens.