Dennis Foss - Academia.edu (original) (raw)

Papers by Dennis Foss

This article cites 39 articles, 21 of which can be accessed free

Veterinary Immunology and Immunopathology

Porcine circovirus type 2 (PCV2) has one of the highest evolutionary rates among DNA viruses. Tra... more Porcine circovirus type 2 (PCV2) has one of the highest evolutionary rates among DNA viruses. Traditionally, PCV2 vaccines have been based on the 2a genotype as this was the first genotype discovered. Today, eight genotypes of PCV2 viruses have been identified, and, taken together with the rapid evolutionary rate, propensity to recombine, and high rate of vaccination, further variation in PCV2 is expected. For these reasons, there is a growing genetic gap between available vaccines and field strains. When selecting vaccines, it is important to consider vaccines that contain T cell epitopes that are well-matched to the circulating strains. To quantify the relatedness between PCV2 vaccines and field strains, we predicted and compared their T cell epitope content and calculated Epitope Content Comparison (EpiCC) scores using established in silico tools. T cell epitopes predicted to bind common class I and class II swine leukocyte antigen (SLA) alleles were identified from two major structural proteins, the capsid (encoded by ORF2) and the replicase (encoded by ORF1). The T cell epitope content of three commercial PCV2a-based vaccines (a baculovirus expressed PCV2a ORF2 [VacAlt], a PCV1-PCV2a chimeric virus vaccine [VacA] and a combination cPCV2a-cPCV2b chimeric virus vaccine [VacAB]) and an experimental PCV2b ORF2-based chimeric virus vaccine [VacB] (Table 1), were compared to that of 161 PCV2 field strains (representing genotypes a-f). The T cell epitope content and conservation between vaccine and field strains varied. While all vaccine strains provided broad coverage of the field strains including heterologous genotypes, none of the vaccines covered all the putative T cell epitopes identified in the field strains. PCV2a-based vaccine strains generally scored higher in terms of conserved epitope content against PCV2a field isolates but were not identical. The PCV2b-based vaccine strain had higher scores against PCV2b and PCV2d field strains. The combination PCV2a-PCV2b vaccine (VacAB) had, on average, the highest EpiCC score. PCV2 continues to evolve and EpiCC analysis provides a new tool to assess the possible impact of virus genetic divergence on T cell epitope coverage of vaccine strains. Given that multiple genotypes are currently found and may co-exist on farms, this analysis suggests that a combination of PCV2a and PCV2b vaccine strains may be required to provide optimal coverage of current and future field isolates.

Virology

Immuno-stimulatory class I-restricted cytotoxic T lymphocytes (CTL) epitopes of porcine reproduct... more Immuno-stimulatory class I-restricted cytotoxic T lymphocytes (CTL) epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) are important for vaccine development. In this study we first determined the expression frequency of swine leukocyte antigen (SLA) class I alleles in commercial pigs in the United States. The SLA genotyping result allowed us to predict potential CTL epitopes from a contemporary strain of PRRSV (RFLP 1-7-4) by using bioinformatic tools. The predicted epitopes were then evaluated in an ex vivo stimulation assay with peripheral blood mononuclear cells isolated from pigs experimentally-infected with PRRSV. Using flow-cytometry analysis, we identified a number of immuno-stimulatory CTL epitopes, including two peptides from GP3 and two from Nsp9 that significantly improved both degranulation marker CD107a and IFN-γ production in cytotoxic CD4+CD8+ T cells, CD8+ T cells, and γδ T cells, and two peptides that inhibited IFN-γ production. These CTL epitopes will aid future vaccine development against PRRSV.

The ISME Journal

Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suff... more Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig-or nonhuman primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100 000 and 15 000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.

PLOS ONE, 2017

Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vacci... more Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs) from these species relative to cells incubated with an isotype control (p<0.001). In addition, the mAb induced significant nitric oxide (p<0.0001) release by bovine macrophages. Furthermore, the mAb upregulated the expression of MHC-II by PBMCs, and stimulated significant (p<0.0001) IL-1α, IL6, IL-8, and TNF-α expression by PBMCs. These results suggest that the mAb 2E4E4 can target and stimulate cells from multiple livestock species and thus, it is a potential candidate for adjuvant development. This is the first study to report an antiswine CD40 agonistic mAb that is also broadly reactive against multiple species.

Vaccine, Sep 14, 2016

Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family ... more Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was ...

Clinical and Vaccine Immunology, 2016

The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at... more The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with ...

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Scientific Reports, 2016

Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known o... more Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known on the metabolism of this bacterium and its impact on the host. In this study, we have revealed the importance of the glutamate-generating metabolism, as shown by a complete depletion of glutamine (Gln) in the medium during H. suis culture. Besides Gln, H. suis can also convert glutathione (GSH) to glutamate, and both reactions are catalyzed by the H. suis γ-glutamyltranspeptidase (GGT). Both for H. pylori and H. suis, it has been hypothesized that the degradation of Gln and GSH may lead to a deficiency for the host, possibly initiating or promoting several pathologies. Therefore the in vivo effect of oral supplementation with Gln and GSH was assessed. Oral supplementation with Gln was shown to temper H. suis induced gastritis and epithelial (hyper)proliferation in Mongolian gerbils. Astonishingly, supplementation of the feed with GSH, another GGT substrate, resulted in inflammation and epithelial proliferation levels returning to baseline levels of uninfected controls. This indicates that Gln and GSH supplementation may help reducing tissue damage caused by Helicobacter infection in both humans and pigs, highlighting their potential as a supportive therapy during and after Helicobacter eradication therapy. Non-Helicobacter (H.) pylori Helicobacter (NHPH) species have been found colonizing the stomach of 0.2-6% of humans patients with severe gastric complaints 1. Infection causes gastritis and peptic ulceration and the relative risk of developing mucosa-associated lymphoid tissue (MALT) lymphoma has been described to be higher with NHPH than with H. pylori 1,2. Several studies have shown that H. suis, a member of the H. heilmannii sensu lato (s.l.) group 3 , is the most prevalent gastric NHPH in humans, which has been described to account for 14% to 78.5% of NHPH infections 4-6. Interestingly, experimental infection studies in rodent models of human gastric disease have confirmed that long-term H. suis infection can lead to the development of gastric MALT lymphoma 7-9. Besides humans, the majority of pigs worldwide are colonized by this bacterium, in which infection causes chronic gastritis and reduced average daily weight gain 10. Transmission of H. suis most likely occurs through contact between pigs and humans 1,11. Presence of viable H. suis bacteria in pork, however, suggests that foodborne infection might also occur 12. A persistent mild chronic gastritis can be observed in human patients after H. heilmannii s.l. eradication treatment with antibiotics and proton-pump-inhibitors 11,13. For H. pylori, it has also been described that after successful eradication in humans, corpus gastritis and dysplasia improve, although they do not completely disappear. Especially antral lesions seem non-responsive after eradication therapy 14. This emphasizes the need for supplements that promote health of the gastric mucosa. Recently, we and others identified the γ-glutamyltranspeptidase (GGT) from H. suis and H. pylori as an important factor causing epithelial cell death and modulating lymphocyte responses 15-18. For all gastric helicobacters, the mode of action of the GGT mostly depends on the breakdown of 2 substrates, glutathione (GSH) and glutamine (Gln), both leading to the production of glutamate 8,19-22. Under certain conditions, GGT-mediated degradation of GSH facilitates the formation of reactive oxygen species, causing lipid peroxidation of cell membranes,

Journal of Swine Health and Production

Objectives: To develop a non-culture-based method to determine levels of Helicobacter suis infect... more Objectives: To develop a non-culture-based method to determine levels of Helicobacter suis infection in porcine stomachs and to test the method in a sample of pigs from a variety of regions in the United States. Materials and methods: A polymerase chain reaction (PCR) assay was developed to quantitate total Helicobacter generic DNA and Helicobacter suis species-specific DNA in pig stomachs. Primers were derived from 16s ribosomal RNA (rRNA) gene sequences, selected on the basis of relative conservation and divergence of sequences across the various Helicobacter species. The assay was standardized using cloned 16s rRNA sequences and was initially tested with DNA isolated from cultured H suis. Gastric mucosal scrapings were collected from pigs in three geographic regions of the United States, including the North (Minnesota and Michigan), East Central (Iowa), and South (Oklahoma and North Carolina). Results: Of a total of 118 pigs tested, approximately half (55.1%; 95% CI, 46.1%-63.8%) were positive for H suis DNA. Helicobacter suis DNA was detected in pigs from all states tested. Implications: Helicobacter suis is present in US pigs and may be relevant to pig health and production. This quantitative PCR assay will facilitate further study of H suis in pigs, including potential therapeutic and prophylactic interventions.

Infection and immunity, 1999

The ability of innate immune cells to differentially respond to various bacterial components prov... more The ability of innate immune cells to differentially respond to various bacterial components provides a mechanism by which the acquired immune response may be tailored to specific pathogens. The response of innate immune cells to bacterial components provides regulatory signals to cognate immune cells. These signals include secreted cytokines and costimulatory molecules, and to a large extent they determine the quantitative and qualitative nature of the immune response. In order to determine if innate immune cells can differentially respond to bacterial components, we compared the responses of macrophages to two bacterially derived molecules, cholera toxin (CT) and lipopolysaccharide (LPS). We found that CT and LPS differentially regulated the expression of interleukin-12 (IL-12) and CD80-CD86 but not that of IL-1beta. LPS and CT each induced IL-1beta expression in macrophages, while only LPS induced IL-12 and only CT induced CD80-CD86. These differences were markedly potentiated in...

Infection and immunity, 1995

An Actinobacillus pleuropneumoniae infection model in swine was established to study the expressi... more An Actinobacillus pleuropneumoniae infection model in swine was established to study the expression of inflammatory cytokines during acute respiratory disease. Lavage fluid, lavage cells consisting primarily of alveolar macrophages, and lung tissue were analyzed for the presence of various cytokines at 2, 4, 8, and 24 h following endotracheal inoculation of A. pleuropneumoniae. Interleukin-1 beta (IL-1) and IL-8 mRNA levels were elevated within 2 h in lavage cells of animals inoculated with A. pleuropneumonia but not in cells from controls treated with saline-bovine serum albumin, based on Northern (RNA blot) analysis. Tumor necrosis factor (TNF) mRNA was present at low levels in all animals, and the level was not increased at any time point. In situ hybridization was more sensitive than Northern blotting and revealed elevations of all three cytokines in lavage cells within 2 to 4 h of A. pleuropneumoniae inoculation. IL-6 was detected in lavage cells by in situ hybridization but no...

Veterinary Immunology and Immunopathology, 1997

Animal Health Research Reviews, 2000

The vast majority of pathogens invade via mucosal surfaces, including those of the intestine. Vac... more The vast majority of pathogens invade via mucosal surfaces, including those of the intestine. Vaccination directly on these surfaces may induce local protective immunity and prevent infection and disease. Although vaccine delivery to the gut mucosa is fraught with obstacles, immunization can be enhanced using adjuvants with properties specific to intestinal immunity. In this review, we present three general mechanisms of vaccine adjuvant function as originally described by Freund, and we discuss these principles with respect to intestinal adjuvants in general and to the prototypical mucosal adjuvant, cholera toxin. The key property of intestinal adjuvants is to induce an immunogenic context for the presentation of the vaccine antigen. The success of oral vaccine adjuvants is determined by their ability to induce a controlled inflammatory response in the gut-associated lymphoid tissues, characterized by the expression of various costimulatory molecules and cytokines. An understanding...

Advances in Veterinary Medicine, 1999

Delivery of protein antigens to the GALT can result in immunity or oral tolerance depending on th... more Delivery of protein antigens to the GALT can result in immunity or oral tolerance depending on the circumstances of the encounter. One mechanism by which mucosal adjuvants can affect these circumstances is by the induction of macrophage cytokines, including IL-1 and IL-12. These cytokines can directly affect the immune response by their effects on antigen-specific T cells and by the induction of IFN-gamma by T cells or NK cells. This IFN-gamma also activates macrophages to up-regulate MHC or costimulatory molecules and by further inducing IL-1 and IL-12. In effect, mucosal adjuvants function both directly and indirectly as activators of antigen presenting cells, resulting in stimulation of the immune response to coincidental antigens. Our studies in swine have shown CT is a potent mucosal adjuvant for CT-B. CT also increased IL-1 and IL-12 mRNA in cultured macrophages, especially after activation with IFN-gamma. The effect of CT on the secretion of bioactive IL-12 protein is currently being investigated. While the mucosal adjuvanticity of CT involves a variety of mechanisms, these findings suggest a role for the induction of the macrophage cytokines IL-1 and IL-12.

Veterinary Immunology and Immunopathology, 2001