Background: Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified.
View Article and Find Full Text PDFThe emergence and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for rapid vaccine development platforms that can be updated to counteract emerging variants of currently circulating and future emerging coronaviruses. Here we report the development of a "train model" subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein (the "engine") linked to a series of flexible receptor binding domains (RBDs; the "cars") derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant, are immunogenic in Syrian hamsters and subsequently provide protection from infection with SARS-CoV-2 VOCs Omicron (BA.
View Article and Find Full Text PDFBackground: Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important infectious diseases for the pig industry. A novel small-scale transmission experiment was designed to assess whether the WUR0000125 (WUR for Wageningen University and Research) PRRS resilience single nucleotide polymorphism (SNP) confers lower susceptibility and infectivity to pigs under natural porcine reproductive and respiratory syndrome virus (PRRSV-2) transmission.
Methods: Commercial full- and half-sib piglets (n = 164) were assigned as either Inoculation, Shedder, or Contact pigs.
Gamma-Delta T cells are a prominent subset of T cells in pigs. However, developmental changes, antigen recognition, cell migration, and their contributions to pathogen clearance remain largely unknown. We have recently shown that porcine γδ T cells express Toll-like receptors (TLRs), and that TLR7/8 stimulation can function as a co-stimulatory signal that complements cytokine-induced signals to enhance INFγ production.
View Article and Find Full Text PDFThe ongoing evolution of SARS-CoV-2 continues to raise new questions regarding the duration of immunity to reinfection with emerging variants. To address these knowledge gaps, controlled investigations in established animal models are needed to assess duration of immunity induced by each SARS-CoV-2 lineage and precisely evaluate the extent of cross-reactivity and cross-protection afforded. Using the Syrian hamster model, we specifically investigated duration of infection acquired immunity to SARS-CoV-2 ancestral Wuhan strain over 12 months.
View Article and Find Full Text PDFIn late 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. It has caused millions of hospitalizations and deaths, despite the use of COVID-19 vaccines. Convalescent plasma and monoclonal antibodies emerged as major therapeutic options for treatment of COVID-19.
View Article and Find Full Text PDFGamma-Delta (γδ) T cells represent a prominent lymphocyte subset in pigs. Their role and function, however, remains largely unknown. Toll-like receptors (TLR) are key receptors for the recognition of pathogens, but so far, it is unknown if porcine γδ T cells express TLRs and therefore have the innate ability to recognize pathogens through pattern recognition receptors.
View Article and Find Full Text PDFHost defense peptides (HDPs) show both antimicrobial and immunomodulatory properties making them important mediators of the host immune system. In humans but also in pigs many HDPs have been identified and important families such as cathelicidins and defensins have been established. In our study, we assessed: (i) the potential interactions that could occur between three peptides (LL37, PR39, and synthetic innate defense regulator (IDR)-1002) and a common TLR ligand called poly(I:C); (ii) the impact of selected peptides on the response of alveolar macrophage (AM) to poly(I:C) stimulation; (iii) the anti-porcine respiratory and reproductive syndrome virus (PRRSV) properties of the peptides; and (iv) their adjuvant potential in a PRRSV challenge experiment after immunization with different vaccine formulations.
View Article and Find Full Text PDFProblem: Induction of the local mucosal immune system within the reproductive tract is widely considered to be a key component in the development of effective prophylactic vaccines to control the spread of sexually transmitted infections. Here, we examine the capacity of the upper reproductive tract to act as a site of immune induction following.
Method Of Study: Two vaccines formulated with a triple adjuvant combination and either recombinant bovine herpesvirus (tgD) protein or ovalbumin (OVA) were delivered at varying doses to the uterine lumen of rabbits and the resulting immune response evaluated after 32 days.
Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.
View Article and Find Full Text PDFInnate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties.
View Article and Find Full Text PDFWhooping cough is a respiratory illness most severe in infants and young children. While the introduction of whole-cell (wP) and acellular pertussis (aP) vaccines has greatly reduced the burden of the disease, pertussis remains a problem in neonates and adolescents. New vaccines are needed that can provide early life and long-lasting protection of infants.
View Article and Find Full Text PDFThe neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs) play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response.
View Article and Find Full Text PDFInterleukin-17 (IL-17) producing cells, referred to as Th17, have recently emerged as a third subset of the T helper (Th) cell family. Studies in mice have demonstrated that Th17 cells and their associated cytokines are involved in several autoimmune diseases and host defense against infection. Murine Th17 cells differentiate from naïve CD4(+) T-cells in the presence of TGFβ and IL-6, however, there are contradicting reports as to the role of TGFβ in the differentiation of human Th17 cells and very little is known about these cells in other animals.
View Article and Find Full Text PDFReal-time quantitative PCR (RT-qPCR) is a critical tool used to evaluate changes in gene expression. The precision of this tool is reliant upon the selection of reference genes whose expression remains unaltered in culture conditions and following stimulation. Stably expressed reference genes are used to normalize data so observed changes in expression are not due to artifacts but rather reflect physiological changes.
View Article and Find Full Text PDFDendritic cells (DCs) are at the interface of innate and adaptive immune responses. Once activated via triggering of their pattern recognition receptors (PRRs), they acquire a mature state and migrate to the lymph nodes where they activate T cells and direct the immune response. Compounds that trigger PRRs are potential vaccine adjuvants, hence in this study we stimulated two porcine DC populations, namely monocyte-derived DCs (MoDCs) and blood DCs (BDCs), with a broad range of toll-like receptors (TLRs) ligands and assessed the activation/maturation state of these porcine DCs.
View Article and Find Full Text PDFVarious dendritic cell (DC) populations exist that differ in phenotype and ability to present antigen to T cells. For example, plasmacytoid DCs (pDCs) are less potent T cell activators compared with conventional DCs (cDCs). Here, we compared porcine blood DCs (BDCs), containing pDCs and cDCs, and monocyte-derived DCs (MoDC), consisting of cDCs, in their phenotype, ability to uptake antigen, activation and maturation and their ability to present antigen to autologous T cells.
View Article and Find Full Text PDFThe assembly of adenovirus particles is a multistep process, in which viral genomic DNA is selected and subsequently inserted into preformed empty capsids. The selective encapsidation of the adenovirus genome is directed by cis-acting packaging motifs, termed A repeats due to their AT-rich character in DNA sequence. A repeats are usually located at the left end of the viral genome.
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