Day 2 :
Keynote Forum
William C Gause
Director, Professor, Rutgers New Jersey Medical School, United States
Keynote: Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion
Time : 10:30 - 11:00
Biography:
William C Gause has received his PhD from Cornell University. He was a Fellow at the National Institutes of Health and was a Faculty Member at the Uniformed Services University (USU) from 1989-2004. In 2004, he has joined New Jersey Medical School as the Senior Associate Dean for Research. In 2016 he became Director of the Rutgers Biomedical Health Sciences Institute for Infectious and Inflammatory Diseases. He has published over 100 papers, served on editorial boards, organized and chaired symposia, and received a number of awards. His research has recently focused on macrophages and their role in inflammation and resistance.
Abstract:
The innate immune cells mediating macro parasite clearance remain largely undefined. We examined their role in acquired resistance to the parasitic nematode, Nippostrongylus brasiliensis (Nb) hypothesizing that they may mediate the markedly accelerated CD4+ cell-independent worm clearance occurring after secondary inoculation. After secondary inoculation, parasitic larvae in the lung are surrounded by macrophages and showed reduced ATP, indicating impaired metabolism. As late as one month after Nb inoculation, lung macrophages, transferred to naive recipients, accelerated parasite clearance. Primed macrophages adhered to larvae in vitro and triggered increased mortality through CD11b-dependent mechanisms. Neutrophil depletion impaired the recall response and depletion of neutrophils in primed mice abrogated the protective effects of transferred macrophages in recipient mice and inhibited their binding to L3. Global transcriptome analyses of sort-purified lung neutrophils from Nb inoculated mice revealed a markedly different expression pattern from lung neutrophils isolated from LPS inculcated mice, indicating that neutrophils, like macrophages, develop a distinct alternatively activated phenotype (N2) after helminth infection. These data thus indicate that differentially activated neutrophils in the context of a type-2 immune response prime a long-lived effector macrophage phenotype that binds metazoan parasites and directly mediates rapid worm damage and clearance.
- Track: Mucosal Diseases
Track: Veterinary Vaccines
Track: Mucosal Immunology of Parasitic Diseases
Location: Melbourne, Australia
Chair
Makoto Yawata
National University of Singapore, Singapore
Session Introduction
Cyril Seillet
University of Melbourne, Australia
Title: Complementarity and redundancy of IL-22-producing innate lymphoid cells
Biography:
Cyril Seillet has completed his PhD in France in 2011 during which he showed the critical role of oestrogens on dendritic cells responses. He was subsequently recruited to The Walter & Eliza Hall Institute in Melbourne where he investigated the transcription factors Id2 and Nfil3 in the development of innate lymphoid cells and dendritic cells. He has published 21 papers in the last five years in top journals in the field including Nat. Immunol., Immunity, J. Exp. Med. and Blood.
Abstract:
The gastrointestinal tract is the largest surface area in the body and forms the major protective barrier. Dysregulation of this mucosal barrier leads to the development of chronic intestinal disorders such as inflammatory bowel disease. Innate lymphoid cells (ILCs) are early effectors of mucosal immunity and are essential to maintain intestinal homeostasis in the gut. Intestinal T-cells and group 3 innate lymphoid (ILC3) cells control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T-cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.
Jawhara Samir
University Lille 2, France
Title: Polymorphisms in the mannose binding lectin gene are associated with the defect of the mannose binding lectin functional activity in Crohn’s disease patients
Time : 11:20-11:50
Biography:
Samir Jawhara is a researcher in Lille University Hospital, France (Inserm U995/2). He was a research fellow in Cleveland Clinic (Cleveland, OH), before returning to Lille University Hospital in 2012. He received his PhD in immunology-microbiology in 2006 from Lille University. The major research interests of his lab are related to host-yeast interactions in the intestine and their impact on intestinal inflammation. He is particularly interested in defining the functions of pattern recognition receptors (PRR), such as mannose binding lectin (MBL), Galectin-3, and Toll-like receptors in the intestine during disease. They also interested in how the human pathogenic yeast Candida albicans may manipulate host innate immune pathways during the intestinal inflammation to cause disease.
Abstract:
Mannose Binding Lectin (MBL) and MBL associated serine proteases (MASP) activate the lectin pathway of the complement system and subsequent inflammatory mechanisms. The functional activity of MBL-MASP complex plays a crucial role in antimicrobial host defenses. Recently, we showed that MBL is locally produced by the intestinal epithelial cells and is required for intestinal homeostasis. Low MBL levels have been associated with Crohn’s disease (CD). An association between MBL deficiency and anti-yeast antibodies (ASCA) is observed in Crohn’s disease (CD) and this MBL deficiency is frequently associated with a severe phenotype of CD. In the present study, we assessed the role of MBL polymorphisms in the modulation of MBL level and activity in CD patients.
Daisy Vanrompay
Ghent University, Belgium
Title: Primary infection with Chlamydia trachomatis L2c in a porcine model produced urogenital pathology similar as in humans and failed to induce protective immune
Time : 11:50-12:20
Biography:
Daisy Vanrompay is the Director of the Laboratory for Immunology and Animal Biotechnology at Ghent University and Director of the Belgian National Diagnostic Reference Laboratory for C. psittaci infections in humans and she is also a Member of PROVAXS.
Abstract:
Background: Chlamydia suis is widespread in commercial pig production and causes important economic losses. Currently, C. suis infections are mainly associated with conjunctivitis and reproductive disorders in sows and boars.
Objectives: The aim was to reveal the characteristics of genital C. suis infection and re-infection in female pigs by studying the immune response, pathology, replication of chlamydia in the genital tract and bacterial excretion.
Methods: Pigs were intravaginally infected and re-infected with C. suis strain S45, the type strain of this species.
Results: S45 is pathogenic for the urogenital tract. Chlamydia replication occurred throughout the urogenital tract, causing inflammation and pathology. The genital infection elicited both cellular and humoral immune responses. Compared to the primo-infection of pigs with C. suis, re-infection was characterized by less severe macroscopic lesions and less chlamydial elementary bodies and inclusions in the urogenital tract. This indicates the development of a certain level of protection following the initial infection. Protective immunity against re-infection coincided with higher chlamydia-specific IgG and IgA antibody titers in sera and vaginal secretions, higher proliferative responses of peripheral blood mononuclear cells (PBMC), higher percentages of B lymphocytes, monocytes and CD8+ T cells and upregulated production of IFN- γ and IL-10 by PBMC.
Conclusions: Although C. suis is often still considered as an insignificant pathogen of pigs, it was demonstrated to be a primary pathogen of the urogenital tract. Furthermore, we established an experimental challenge model, suitable for further pathological and immunological investigations and will probably also be useful for studying vaccine development.
Paraic O Cuiv
The University of Queensland, Australia
Title: From bugs to drugs: Expediting the discovery of immunoregulatory bioactives from the human gut microbiota to drive the development of novel anti-inflammatory therapeutics
Time : 12:20-12:50
Biography:
Paraic O Cuiv is Research Fellow at the University of Queensland Diamantina Institute where he has a long standing interest in the human gut microbiota and its role in the aetiology of chronic gut diseases. His expertise is primarily in microbiology, bacterial genetics and genomics and his research is currently focused on these three distinct areas.
Abstract:
The incidences of chronic gut diseases in Australia including inflammatory bowel diseases, colorectal cancer, and obesity are amongst the highest internationally. In addition to host genetic, environmental and lifestyle factors it is now increasingly recognized that the microbial community resident in the gut (gut microbiota) has a significant influence on disease risk. Recent research has revealed that the gut microbiota of healthy individuals is characterized by a “core microbiota” of up to 125 bacterial species that are numerically abundant and widely shared amongst individuals. Furthermore, the structure of the core gut microbiota differs between the healthy and diseased gut, these differences are coincident with the onset of active disease and a restoration of key species is associated with improvements in gut health. Many core gut microbes are unrepresented by cultured isolates however several of the isolates that are available have been shown to modulate the host inflammatory response and regulate the development and/or effector functions of different immune cell populations, thus helping maintain gut homeostasis. These “bioactives” could support the development of novel therapeutics however despite a wealth of genomic and metabolomic data the vast majority of the immunomodulatory functionalities encoded by the microbiota remain cryptic. We have developed a new methodology termed “metaparental mating” that enables genetically tractable core bacteria to be rapidly recovered from complex gut communities and that has the potential to transform our ability to functionally characterize gut bacteria. We anticipate that this will support the discovery of immunomodulatory bioactives and expedite the development of novel anti-inflammatory therapeutics.
Akram Abouie Mehrizi
Pasteur Institute of Iran, Iran
Title: Th1 immune responses to Plasmodium falciparum merozoite surface protein 1 in combination with poly I:C/alum in BALB/c mice
Biography:
Akram Abouie Mehrizi has completed her PhD from National Institute of Genetic Engineering and Biotechnology and Postdoctoral studies from Pasteur Institute of Iran. She is an Assistant Professor in MVRG at Pasteur Institute of Iran, working on malaria vaccine development as her main field of interest. Her strategies in vaccine development are to improve the vaccines by new vaccine candidate antigens, expression systems (Bacteria and microalgae) and adjuvants. She has published more than 20 papers in reputed journals.
Abstract:
The C-terminal region of Plasmodium falciparum Merozoite Surface protein 1 (PfMSP-142) is a leading malaria vaccine candidate antigen. Nevertheless, the results of clinical trials of MSP-1 based vaccines have not shown complete efficacy. In this regard, the main obstacle is the lack of potent adjuvants suitable for using in human. In this study, to induce high titer of total antibodies and polarized Th1 immune responses against PfMSP-142, poly I:C as a potent and human compatible adjuvant was used. For this purpose, the PfMSP-142 gene was cloned and expressed in E. coli M15-pQE30 expression system. Five test groups of BALB/c mice were immunized with affinity purified recombinant PfMSP-142 antigen alone or in combination with poly I:C, poly I:C/alum, alum or CFA/IFA adjuvants. The control groups received PBS1 or corresponding adjuvants without antigen. Immunization was carried out three times, 2 weeks intervals via subcutaneous rout. Anti-PfMSP-142 IgG and IgG subclasses were measured 10 days after last immunization. The results showed that antibody response was highest in the mice groups that received rPfMSP-142+poly I:C/alum. Interestingly, among the five test groups, the level of IgG2a antibody as the Th1 response was significantly increased in the mice groups that received rPfMSP-142 in combination with poly I:C/alum or poly I:C. In conclusion, the results showed that in compare with CFA/IFA adjuvant, the poly I:C/alum combination adjuvant could improve the immune responses to rPfMSP-142 antigen, which could imply that poly I:C is a potent adjuvant that elicits Th1 immune responses against Plasmodium antigens.
Ghorbanali Rahimian
Shahrekord University of Medical Sciences, Iran
Title: Mucosal IL-21 mRNA expression level is high in patients with H. pylori and is associated with the severity of gastritis
Biography:
Ghorbanali Rahimian has completed his MD from Tehran University of Medical Sciences. He has published more than 15 papers in reputed journals.
Abstract:
Helicobacter pylori (H. pylori) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells. Different clinical forms of the infection may reflect distinctive patterns of cytokine expression. IL-17, IL-21, IL-22 and IL-23 have been reported to be involved in H. pylori-induced gastric mucosal inflammation but the details and relationship to different patterns of inflammation and virulence factors remain unclear. Therefore we examined IL-21 in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors cagA and vacA allelic variants in H. pylori-infected on the mucosal IL-21 mRNA level in gastric mucosa. We also determined correlation between mucosal IL-21 mRNA levels and types of disease as well as grade of gastritis. Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients. Mucosal IL-21 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time PCR. Presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR. IL-21 mRNA expression was significantly more in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was no association between virulence factors and IL-21 mRNA expression. In conclusions, mucosal IL-21 expression level is increased in patients with H. pylori and is associated with the severity of gastritis. Therefore, we believe that IL-21 might be involved in the pathogenesis of H. pylori and might be an index of the severity of chronic gastritis.
Biography:
Hailelule Aleme is an Assistant Professor of Dilla University, Ethiopia.
Abstract:
In Ethiopia only a few studies on the seroprevalence of toxoplasmosis have been carried out among HIV/AIDS patients. The objective of this study was to determine the seroprevalence of toxoplasmosis among HIV/AIDS patients at Tikur Anbessa Specialized Hospital, Ethiopia and to determine risk factors associated with seroprevalence.
- Workshop on TRIF regulates CXCR5+ T helper cells in the intestine by Masayuki Fukata, Cedars-Sinai Medical Center, USA
Location: Melbourne, Australia
- Track: Mucosal Vaccination
Track: Mucosal Immunology of Host Defenses
Track: Mucosal Vaccines Adjuvants
Track: Mucosal Immunity and Vaccines
Track: Mucosal Immunology of Parasitic Diseases
Location: Melbourne, Australia
Chair
Damien John Zanker
La Trobe University, Australia
Session Introduction
Eliana Marino
Monash University, Australia
Title: Dietary manipulation of gut microbial metabolites prevents autoimmune diabetes
Biography:
Eliana Marino is the Head of the Immunology and Diabetes Laboratory at the School of Biomedical Sciences, Monash University, Australia. Her career has been characterized by several important research advances in immune cell migration, function and distribution in diabetogenic compartments as well in mucosal immunology. She has established a successful research program to further understand the interactions between the immune system and the gut bacteria or “microbiota” through the biosynthesis of metabolites and their impact in inflammatory and metabolic diabetes and related complications such as kidney disease. Her research has been published in more than 15 peer-reviewed articles in journals e.g. Nature Communications, European Journal of Immunology, Journal of Immunology, and Diabetes.
Abstract:
Diet and gut microbial ecology may underlie the increasing incidence of certain inflammatory diseases. Here, we found that key features of autoimmune diabetes in NOD mice, such as gender differences and protection in MyD88-/- NOD mice, correlated closely with blood and fecal concentrations of the short chain fatty acids (SCFAs) acetate and butyrate. We used specialized diets to deliver high concentrations of acetate and butyrate to the colon and hepatic portal vein of NOD mice, when tolerance to islet antigens has already been broken. High acetate or butyrate yielding diets significantly reduced progression to diabetes, through effects on the colonic microbiota, improved gut epithelial integrity and reduced concentrations of IL-21 and TNFα. Both acetate and butyrate diets led to dramatically decreased numbers of autoreactive T-cells in lymphoid tissues. A high butyrate yielding diet promoted conversion of naive T-cells into Foxp3+ Treg cells in vivo, through histone modification at the Foxp3 promoter that led to increased numbers of Treg cells in both the gut and the periphery. In contrast, an acetate yielding diet inhibited histone deacetylase-3 transcription in B-cells, which led to markedly reduced expression of CD86 and MHCI and reduced capacity to expand autoreactive CD8+ T-cells in vivo. Control of autoimmune T-cell frequencies and protection from diabetes relied in part on the metabolite sensor GPR43, a receptor for both acetate and butyrate. Specialized diets that yield high acetate or butyrate may represent an effective non-pharmacologic means to limit autoreactive T-cell numbers and prevent autoimmune disease progression.
Paul Foster
The University of Newcastle, Australia
Title: Role of IL-36 in pathogen induced exacerbation of asthma
Biography:
Paul Foster is the Director of the Priority Research Centre for Asthma and Respiratory Disease; the Virus, Infection/Immunity, Vaccines and Asthma Program, Hunter Medical Research Institute and the Cooperative Research Centre (CRC) for Asthma and Airways (Newcastle node). He also currently holds the Chair of Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle.
Abstract:
Asthma is an inflammatory disorder that was once treated as a single disease. Conventional asthma treatment involves the use of inhaled corticosteroids and bronchodilators to inhibit inflammation and airway constriction. However approximately 20% of asthma patients are non-responsive to steroid treatment and have increased risk of hospitalization and death. Respiratory infections are thought to be one of the major risk factors that trigger steroid resistant exacerbations. In these patients innate inflammatory mediators and cells are linked to pathogenesis and disease severity. Our studies investigations have identified novel roles of interleukin (IL)-36 family cytokines in regulating airway inflammation and alterations in lung function during infection and pathogen induced exacerbation of asthma. We found that the expression of IL-36γ was activated by pathogen associated molecular pattern derived from bacteria and viruses in macrophages. Administration of recombinant IL-36γ, in vitro (bronchial epithelial cells) and in vivo (lungs), increased TNF-α, IL-1β, IL-6, IL-33, IL-13, and CXCL1 expression. Interestingly, treatment with IL-36γ also increased recruitment of both type-2 innate lymphoid cells (ILC2) and dendritic cells (DC), both are critical for asthma pathogenesis. We next sought to determine the importance of IL-36γ in asthma using a well characterized murine model of allergic airway disease model. Mice were sensitized and challenged with ovalbumin (OVA) to induce hallmark features of asthma. During allergen challenge, recombinant IL-36γ was administered intranasally. Pulmonary function was then assessed. Mice treated with IL-36γ became insensitive to corticosteroid therapy. In conclusion, we show that infections that trigger asthma exacerbations are linked to IL-36 production and that delivery of this cytokine to the airways results in steroid resistant AHR and neutrophilic inflammation. Our results suggest that IL-36γ could be a potential therapeutics target for neutrophilic and severe asthmatics.
Mehfuz Zaman
Griffith University, Australia
Title: Liposomal mucosal vaccine delivery system: Immunogenecity, inflammatory response and protection from group A streptococcus challenge
Time : 12:00-12:30
Biography:
Mehfuz Zaman is a NHMRC Early Career Fellow. He has completed his BSc, PhD from the University of Queensland in Medicinal Chemistry. His research interests are drug delivery, sub-unit vaccines, adjuvants, lipids and peptides. His research aims to rationally design and develop vaccines by understanding the mechanisms by which pathogens induce immune response and correlates of protective immunity.
Abstract:
Group A streptococcus (GAS) infections are extremely important clinical problems due to their global health burden. Rheumatic fever and rheumatic heart disease are responsible for the majority of morbidity and mortality (estimated at 12 million cases annually with 380,000 fatalities). Current leading GAS vaccine candidates are challenged by their limited efficacy against primary GAS infections of the upper respiratory tract (URT) due to lack of mucosal antibody responses. This is due in large part to the lack of human approved mucosal adjuvants. We describe an innovative vaccine strategy to induce mucosal and serum antibodies against GAS in animal models based on an important neutralizing antibody determinant from the cell surface GAS M protein. Incorporation of carrier protein and M protein-based B-cell epitopes onto liposomal vesicles induce potent serum and mucosal antibodies without the need for an additional adjuvant. Immunized mice were capable of preventing GAS infection post-challenge. The size of liposomes influenced the immune response and antigen-specific inflammatory response. Liposomes could be lyophilized to a powder form negating cold-chain storage and stability issues, highlighting the promise to translate from murine studies to application in humans as a vaccine candidate. The study provides important mechanistic insights into how liposomal particulate delivery systems can collectively induce the desired mucosal immune responses to combat GAS infection. The strategy reported here is relevant to the development of subunit mucosal vaccines against other pathogenic organisms.
Masayuki Fukata
Cedars-Sinai Medical Center, USA
Title: Innate immune regulation of T-helper (Th) cell homeostasis in the intestine
Time : 12:30-13:00
Biography:
Masayuki Fukata is a Physician Scientist in the field of Gastroenterology and Mucosal Immunology. He has obtained his MD and PhD from the Jikei University School of Medicine in Tokyo Japan and he was certified by Educational Commission for Foreign Medical Graduates (ECFMG) in the US. He was trained in Clinical Gastroenterology at the Jikei University Hospital and completed Postdoctoral training at the Cedars-Sinai Medical Center in LA as well as Mount Sinai School of Medicine in NY. He is currently a Faculty at the division of Gastroenterology at Cedars-Sinai and Assistant Professor of Medicine at the University of California Los Angeles.
Abstract:
Intestinal mucosa is a large reservoir of Th cells in our body, where Th cells differentiation is balanced. The maintenance of this balance in Th cell subtypes is crucial for immune homeostasis and a biased proportion of Th subtype results in development of chronic inflammatory diseases. The maintenance of Th cells in intestinal mucosa largely involves luminal bacteria which constantly interact with local innate immune cells of the host. Recent discoveries revealed that many immune disorders involve this host bacterial interaction in intestinal mucosa. On the other hand, most immune disorders are associated with abnormal Th cell activation. Now, what is still missing in our knowledge is the link between intestinal bacteria and abnormal T cell activation. We have sought to determine the role of innate immunity in the regulation of Th cell homeostasis in the intestine because innate immunity directly responds to bacteria and has the ability to promote Th cell differentiations. We put a special emphasis on TRIF (TIR domain containing adapter inducing interferon-β) signaling as it signals in response to Gram negative bacteria and is known to play an important role in antigen specific Th cell differentiation. We found that absence of TRIF skews Th cells to Th17 subtype and leads to aberrant Th cell plasticity. It also results in increased generation of central memory T cells and follicular helper (Tfh) cells. Since TRIF signaling can be selectively manipulated, targeting TRIF may provide a variety of opportunities to treat immunological diseases and establish more effective vaccine strategies.
Biography:
Sevda Senel is a Professor of Pharmaceutical Technology. Her current research area involves mucosal drug/vaccine delivery and dental drug delivery. She is currently leading a project on local vaccine production in Turkey through a Ministry-Industry-Academic collaboration. She serves on the Evaluation Committee of Vaccine Products at National Medicines Agency and Advisory Board on Vaccines at National Research Council. She has served as the President of the EUCHIS (2009-2013). She has received the CRS-InterVet 2005 Best Paper Award, 2005 Novartis Research Fund-Pharmaceutical Technology Best Paper Award, 2010 Distinguished Scientist Award by the Academy of Science of the Turkish Pharmacists Association and 2011 Hacettepe University Science Award.
Abstract:
One of the most important strategies for the development of effective new vaccines is the selection and use of a suitable adjuvant. A wide variety of natural and/or synthetic molecules and delivery systems have been investigated as adjuvants/delivery systems to enhance the immune responses of subunit vaccines. They act by improving pathogen recognition and elicit a response similar to the natural innate immune response. A better understanding of the mechanism of action of these adjuvants is crucial to obtain efficient immune responses and appropriate memory. Composition of the adjuvant as well as its physical parameters such as particle size surface charge has significant impact on the overall performance of that adjuvant and the potency of the vaccine. Furthermore, knowledge on adjuvants in regard to regulatory requirements for quality, safety and efficacy needs to be expanded. Chitosan, which is a cationic polymer derived from chitin obtained from crustacean and insect skeletons, is a very promising biopolymer both as an adjuvant and delivery vehicle for antigens, especially for mucosal immunization in human and animals. Due to its properties such as bioadhesivity, biocompatibility, biodegradability and mucosal penetration enhancing effect, chitosan offers an advantage over other systems which are under investigation for mucosal delivery of antigens. In this presentation, after addressing the importance of adjuvants in vaccine development, the recent studies of our group as well as other groups on application of chitosan as adjuvant will be reviewed.
Damien John Zanker
La Trobe University, Australia
Title: Enhancing residential memory T-cell accumulation using alternate immunization site vaccination
Time : 14:20-14:50
Biography:
Damien John Zanker has completed his Bachelor of Science (Hons) degree in Physiology at the University of Melbourne studying therapeutic treatments of Retinopathy of Prematurity. In 2005, he began Research at the Ludwig Institute for Cancer Research at the Austin Hospital before undertaking a PhD through the University of Melbourne in 2008. His studies involved assessing the contribution of the immunoproteasome to generate peptides for immune responses as well as identifying novel non immune roles for this highly specialized type of proteasome. He is a Member of the NHMRC Influenza Program and currently researches CD8+ T cell immunity at La Trobe University, Australia.
Abstract:
Neutralizing antibodies are highly specific for a particular antigen. Viruses such as Influenza-A is commonly mutant to render strain specific neutralizing antibodies non functional against future infecting strains. Because of this, current antibody based influenza vaccines require reformulation annually. However, antigenic peptides that stimulate CD8+ T cell responses commonly arise from internal proteins that rarely mutate from antigenic drift. Due to this, memory CD8+ T cells are thought to be the most promising candidate to target for a cross strain universal influenza vaccine. The residential memory T-cell subset (TRM) is proposed as the frontline defense against pathogen re-encounter as previous studies have demonstrated this subset does not leave its tissue. Using a prime boost protocol, we wished to discover novel ways to enhance TRM numbers at the infection site in mice. Counter intuitively, we identified that initially priming an alternate site and boosting at the desired site dramatically enhanced the responding and memory T-cell pool in the lung. Using this alternate immunization technique, we also showed that peripheral effector memory T-cells were capable of transforming into lung TRM. This led us to believe that only particular antigen presenting cells were capable of inducing TRM formation. We also discovered that TRM formation was productive infection dependent and was required to protect against lethal re-infection. Together, by circumventing primary TRM formation, we were able to boost TRM at a desired site by an alternate immunization site strategy and believe this is an effective method to enhance TRM formation in the absence of adjuvant administration.
Makoto Yawata
National University of Singapore, Singapore
Title: The conjunctiva as a site for investigation of human mucosal immunology in situ elucidating the mechanisms of immune escape in adenovirus induced epidemic keratoconjunctivitis
Time : 14:50-15:20
Biography:
Makoto Yawata is an Assistant Professor at the Department of Pediatrics, School of Medicine, National University of Singapore and Principal Investigator at Singapore Institute for Clinical Sciences, Singapore. As a Physician, he practiced in Rheumatology and Clinical Immunology in Japan. He proceeded to train as a Postdoctoral Fellow in Professor Peter Parham’s Laboratory in Stanford University before joining the National University of Singapore as Faculty. His research activities centers on the basic and clinical aspects of the immunobiology and genetics of human natural killer cells. As an Academic Educator, he trains Physicians in acquiring the skills necessary to conduct clinical investigations as curriculum director of a nationwide program. He currently serves as Associate Editor for ‘Immunology’, an official journal of the British Society for Immunology.
Abstract:
Amongst the various mucosal surfaces in the human body, the ocular surface is unique in that the tissues are exposed to the eternal environment and is readily accessible with minimally invasive means. Although the conjunctiva is a mucosal surface that is a site prone to infections, the immune systems operating within the conjunctiva are yet vastly underexplored. Here we describe the mechanisms of an innate immune response against adenovirus infection, where members of the group D family of viruses are specifically known to trigger a severe form of inflammation: epidemic keratoconjunctivitis (EKC). In our ongoing study of the innate immune responses in clinical cases of EKC, we have been able to monitor the dynamic changes in natural killer cell phenotypes and function over the course of virus infection. To our knowledge, this is one of the unique instances where such immune monitoring has been possible over the course of infection at a human mucosal surface. Based on the clinical observations, we have verified through in vitro experimentation the mechanisms by which group D adenoviruses but not other adenovirus types specifically act on epidermal cells to subvert NK cell responses as a form of immune escape. This study is a demonstration as to how the conjunctiva can be viewed as one promising site for human mucosal research in situ.
Qian Yang
Nanjing Agricultural University, China
Title: Immune responses induced by recombinant Bacillus subtilis expressing the spike protein of transmissible gastroenteritis virus in pigs
Time : 15:20-15:50
Biography:
Qian Yang has completed her PhD from Nanjing Agricultural University. She mainly engaged in mucosal immunity and host pathogen interactions work. She has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Transmissible gastroenteritis (TGE) causes severe diarrhea in suckling piglets, results in enormous economic loss in swine-producing areas of the world. To develop an effective, safe, and convenient vaccine for the prevention of TGE, we have constructed a recombinant Bacillus subtilis strain (B. subtilis CotGSG) displaying the transmissible gastroenteritis virus (TGEV) spike (S) protein and discussed its immune function to intestinal submucosal dendritic cells (DCs). Our results showed that the recombinant B. subtilis had the ability to recruit more DCs to sample B. subtilis CotGSG, migrate to MLNs, and induce immune responses. Immunized piglets with B. subtilis CotGSG could significantly elevate the specific SIgA titers in feces, IgG titers and neutralizing antibodies in serum. Collectively, our results suggested that recombinant B. subtilis CotGSG expressing the TGEV S protein could effectively induce immune responses via DCs, and provided a perspective on potential novel strategy and approach that may be applicable to the development of the next generation of TGEV vaccines.
- Video Presentation
Location: Melbourne, Australia
Session Introduction
Erica L Herzog
Yale School of Medicine, USA
Title: Neuroimmune molecules in human lung fibrosis
Biography:
Erica L Herzog is an Associate Professor of Medicine in the section of Pulmonary, Critical Care and Sleep at Yale School of Medicine. She directs YALE-ILD, the Interstitial Lung Disease Center of Excellence and conducts translational research in the field of pulmonary fibrosis. She has authored over 50 peer reviewed publications and is received by several NIH awards.
Abstract:
Idiopathic pulmonary fibrosis (IPF) is an incurable condition characterized by the progressive accumulation of scar tissue in the adult human lung. It typically leads to death within approximately three years of diagnosis and while several pharmacologic agents can delay disease progression, the benefit of these interventions is limited, heterogeneous and accompanied by toxicity. Current paradigms of pulmonary fibrosis propose this process to result from a mismatch between epithelial cell injury and excessive fibroblast repair responses that may be amplified by interactions with macrophages and understanding all aspects of fibrogenesis is of particular importance in IPF, where patients present with established disease. An emerging interest in this area is the contribution of neuroimmune molecules to these processes. Our laboratory was the first to study this class of proteins in the context of human lung disease when we defined the association of the GPI-anchored membrane protein Semaphorin 7a with pulmonary fibrosis. Sema 7a regulates inflammatory responses via the competing effects of α1β1 integrin and the transmembrane protein Plexin C1. We have shown this interaction to be present in several forms of mammalian lung fibrosis and inflammation where Sema 7a’s stimulatory effects are enacted via an integrin-mediated process that is opposed by Plexin C1. We have also found a novel role for the laminin-like neuronal guidance protein Netrin-1 in the integrin-mediated processes and have detected altered expression of all of these components in IPF. Further study of this area might lead to new therapeutic insights into lung injury and pathologic remodeling.
- Mucosal Immunology of Infectious Diseases
Location: Australia
Session Introduction
Daisy Vanrompay
Ghent University,Belgium
Title: Primary infection with Chlamydia trachomatis L2c in a porcine model produced urogenital pathology similar as in humans and failed to induce protective immune responses against re-infection
Biography:
Daisy Vanrompay is the Director of the Laboratory for Immunology and Animal Biotechnology at Ghent University and Director of the Belgian National Diagnostic Reference Laboratory for C. psittaci infections in humans and she is also a Member of PROVAXS.
Abstract:
We evaluated the pathogenesis, pathology and immune response of a female genital tract infection with Chlamydia trachomatis L2c, the most recently discovered lymphogranuloma venereum strain, using a porcine model of sexually transmitted infection. Pigs were mock infected, infected once or infected and re-infected intravaginally and samples were obtained for chlamydial culture, gross and microscopic pathology and humoral and cell-mediated immunity. Intravaginal inoculation of pigs with this bacterium resulted in an infection that was confined to the urogenital tract, where inflammation and pathology were caused that resembled what is seen in human infection. Re-infection resulted in more severe gross pathology than primary infection and chlamydial colonization of the urogenital tract was similar for primary infected and re-infected pigs. This indicates that primary infection failed to induce protective immune responses against re-infection. Indeed, the proliferative responses of mononuclear cells from blood and lymphoid tissues to C. trachomatis strain L2c were never statistically different among groups, suggesting that C. trachomatis specific lymphocytes were not generated following infection or re-infection. Nevertheless, antichlamydial antibodies were elicited in sera and vaginal secretions after primary infection and re-infection clearly demonstrating a secondary systemic and mucosal antibody response. The porcine model is relevant for evaluating immune and pathogenic responses for emerging and known C. trachomatis strains to advance drug and/or vaccine development in humans.
Ibrahim Mohamed Saeed Abduwahid Shnawa
University of Qasim, Iraq
Title: Mucosal immunology of human bacterial infectious diseases: Personal view
Biography:
Ibrahim Mohamed Saeed Abduwahid Shnawa has completed his PhD from University of Mosul, Iraq. He is a Professor and he has published six books in various aspects of immunology (Amazon, USA) and 100 papers in regional and international journals and has been served as an Editorial Board Member in the International Science Index (WASET), Science Alert Journals and Expert Review of Immunology Vaccine and Informatics Journal.
Abstract:
Mucosal surfaces interplay a crucial role in immune defenses against human infectious diseases. Mucosal antibodies and mucosal immune cells were separated from the clinical materials corresponding to each disease case. The associated causals were isolated, identified and cell free culture filtrate (CFCF) as well as somatic antigens (SA) were made. Mucosal antibodies (MABs) and mucosal immune cells (MICs) were reacted with CFCF and SA using passive hem-agglutination (PHA), standard tube agglutination (STA) and leukocyte inhibitory factor (LIF). Mucosal infections (MI) were either inducing humoral mucosal and systemic immune responses or humoral as well as cellular immune responses both at mucosal surfaces and peripheral blood. The patients herd immune responses were found to be of three fractions; low, moderate and high immune responders. Moderate responders were the major population fraction. Mucosal antibodies and mucosal immune cells can be of use as probes helpful for detection of mucosal infections in human beings.
- Poster Presentation
Location: Melbourne, Australia
Session Introduction
Daisy Vanrompay
Ghent University, Belgium
Title: Primary infection with Chlamydia trachomatis L2c in a porcine model produced urogenital pathology similar as in humans and failed to induce protective immune responses against re-infection
Biography:
Daisy Vanrompay is the Director of the Laboratory for Immunology and Animal Biotechnology at Ghent University and Director of the Belgian National Diagnostic Reference Laboratory for C. psittaci infections in humans and she is also a Member of PROVAXS.
Abstract:
We evaluated the pathogenesis, pathology and immune response of a female genital tract infection with Chlamydia trachomatis L2c, the most recently discovered lymphogranuloma venereum strain, using a porcine model of sexually transmitted infection. Pigs were mock infected, infected once or infected and re-infected intravaginally and samples were obtained for chlamydial culture, gross and microscopic pathology and humoral and cell-mediated immunity. Intravaginal inoculation of pigs with this bacterium resulted in an infection that was confined to the urogenital tract, where inflammation and pathology were caused that resembled what is seen in human infection. Re-infection resulted in more severe gross pathology than primary infection and chlamydial colonization of the urogenital tract was similar for primary infected and re-infected pigs. This indicates that primary infection failed to induce protective immune responses against re-infection. Indeed, the proliferative responses of mononuclear cells from blood and lymphoid tissues to C. trachomatis strain L2c were never statistically different among groups, suggesting that C. trachomatis specific lymphocytes were not generated following infection or re-infection. Nevertheless, antichlamydial antibodies were elicited in sera and vaginal secretions after primary infection and re-infection clearly demonstrating a secondary systemic and mucosal antibody response. The porcine model is relevant for evaluating immune and pathogenic responses for emerging and known C. trachomatis strains to advance drug and/or vaccine development in humans.
- Mucosal Vaccines Adjuvants
Location: Australia
Biography:
Sevda Senel is a Professor of Pharmaceutical Technology. Her current research area involves mucosal drug/vaccine delivery and dental drug delivery. She is currently leading a project on local vaccine production in Turkey through a Ministry-Industry-Academic collaboration. She serves on the Evaluation Committee of Vaccine Products at National Medicines Agency and Advisory Board on Vaccines at National Research Council. She has served as the President of the EUCHIS (2009-2013). She has received the CRS-InterVet 2005 Best Paper Award, 2005 Novartis Research Fund-Pharmaceutical Technology Best Paper Award, 2010 Distinguished Scientist Award by the Academy of Science of the Turkish Pharmacists Association and 2011 Hacettepe University Science Award.
Abstract:
One of the most important strategies for the development of effective new vaccines is the selection and use of a suitable adjuvant. A wide variety of natural and/or synthetic molecules and delivery systems have been investigated as adjuvants/delivery systems to enhance the immune responses of subunit vaccines. They act by improving pathogen recognition and elicit a response similar to the natural innate immune response. A better understanding of the mechanism of action of these adjuvants is crucial to obtain efficient immune responses and appropriate memory. Composition of the adjuvant as well as its physical parameters such as particle size surface charge has significant impact on the overall performance of that adjuvant and the potency of the vaccine. Furthermore, knowledge on adjuvants in regard to regulatory requirements for quality, safety and efficacy needs to be expanded. Chitosan, which is a cationic polymer derived from chitin obtained from crustacean and insect skeletons, is a very promising biopolymer both as an adjuvant and delivery vehicle for antigens, especially for mucosal immunization in human and animals. Due to its properties such as bioadhesivity, biocompatibility, biodegradability and mucosal penetration enhancing effect, chitosan offers an advantage over other systems which are under investigation for mucosal delivery of antigens. In this presentation, after addressing the importance of adjuvants in vaccine development, the recent studies of our group as well as other groups on application of chitosan as adjuvant will be reviewed.
- Innate Immunity in Mucosal Immune System
Location: Australia
Session Introduction
Masayuki Fukata
Cedars-Sinai Medical Center, USA
Title: Innate immune regulation of T-helper (Th) cell homeostasis in the intestine
Biography:
Masayuki Fukata is a Physician Scientist in the field of Gastroenterology and Mucosal Immunology. He has obtained his MD and PhD from the Jikei University School of Medicine in Tokyo Japan and he was certified by Educational Commission for Foreign Medical Graduates (ECFMG) in the US. He was trained in Clinical Gastroenterology at the Jikei University Hospital and completed Postdoctoral training at the Cedars-Sinai Medical Center in LA as well as Mount Sinai School of Medicine in NY. He is currently a Faculty at the division of Gastroenterology at Cedars-Sinai and Assistant Professor of Medicine at the University of California Los Angeles.
Abstract:
Intestinal mucosa is a large reservoir of Th cells in our body, where Th cells differentiation is balanced. The maintenance of this balance in Th cell subtypes is crucial for immune homeostasis and a biased proportion of Th subtype results in development of chronic inflammatory diseases. The maintenance of Th cells in intestinal mucosa largely involves luminal bacteria which constantly interact with local innate immune cells of the host. Recent discoveries revealed that many immune disorders involve this host bacterial interaction in intestinal mucosa. On the other hand, most immune disorders are associated with abnormal Th cell activation. Now, what is still missing in our knowledge is the link between intestinal bacteria and abnormal T cell activation. We have sought to determine the role of innate immunity in the regulation of Th cell homeostasis in the intestine because innate immunity directly responds to bacteria and has the ability to promote Th cell differentiations. We put a special emphasis on TRIF (TIR domain containing adapter inducing interferon-β) signaling as it signals in response to Gram negative bacteria and is known to play an important role in antigen specific Th cell differentiation. We found that absence of TRIF skews Th cells to Th17 subtype and leads to aberrant Th cell plasticity. It also results in increased generation of central memory T cells and follicular helper (Tfh) cells. Since TRIF signaling can be selectively manipulated, targeting TRIF may provide a variety of opportunities to treat immunological diseases and establish more effective vaccine strategies.
- Mucosal Immunity and Vaccines
Location: Australia
Session Introduction
Damien John Zanker
La Trobe University, Australia
Title: Enhancing residential memory T-cell accumulation using alternate immunization site vaccination
Biography:
Damien John Zanker has completed his Bachelor of Science (Hons) degree in Physiology at the University of Melbourne studying therapeutic treatments of Retinopathy of Prematurity. In 2005, he began Research at the Ludwig Institute for Cancer Research at the Austin Hospital before undertaking a PhD through the University of Melbourne in 2008. His studies involved assessing the contribution of the immunoproteasome to generate peptides for immune responses as well as identifying novel non immune roles for this highly specialized type of proteasome. He is a Member of the NHMRC Influenza Program and currently researches CD8+ T cell immunity at La Trobe University, Australia.
Abstract:
Neutralizing antibodies are highly specific for a particular antigen. Viruses such as Influenza-A is commonly mutant to render strain specific neutralizing antibodies non functional against future infecting strains. Because of this, current antibody based influenza vaccines require reformulation annually. However, antigenic peptides that stimulate CD8+ T cell responses commonly arise from internal proteins that rarely mutate from antigenic drift. Due to this, memory CD8+ T cells are thought to be the most promising candidate to target for a cross strain universal influenza vaccine. The residential memory T-cell subset (TRM) is proposed as the frontline defense against pathogen re-encounter as previous studies have demonstrated this subset does not leave its tissue. Using a prime boost protocol, we wished to discover novel ways to enhance TRM numbers at the infection site in mice. Counter intuitively, we identified that initially priming an alternate site and boosting at the desired site dramatically enhanced the responding and memory T-cell pool in the lung. Using this alternate immunization technique, we also showed that peripheral effector memory T-cells were capable of transforming into lung TRM. This led us to believe that only particular antigen presenting cells were capable of inducing TRM formation. We also discovered that TRM formation was productive infection dependent and was required to protect against lethal re-infection. Together, by circumventing primary TRM formation, we were able to boost TRM at a desired site by an alternate immunization site strategy and believe this is an effective method to enhance TRM formation in the absence of adjuvant administration.
Qian Yang
Nanjing Agricultural University, China
Title: Immune responses induced by recombinant Bacillus subtilis expressing the spike protein of transmissible gastroenteritis virus in pigs
Biography:
Qian Yang has completed her PhD from Nanjing Agricultural University. She mainly engaged in mucosal immunity and host pathogen interactions work. She has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Transmissible gastroenteritis (TGE) causes severe diarrhea in suckling piglets, results in enormous economic loss in swine-producing areas of the world. To develop an effective, safe, and convenient vaccine for the prevention of TGE, we have constructed a recombinant Bacillus subtilis strain (B. subtilis CotGSG) displaying the transmissible gastroenteritis virus (TGEV) spike (S) protein and discussed its immune function to intestinal sub-mucosal dendritic cells (DCs). Our results showed that the recombinant B. subtilis had the ability to recruit more DCs to sample B. subtilis CotGSG, migrate to MLNs and induce immune responses. Immunized piglets with B. subtilis CotGSG could significantly elevate the specific SIgA titers in feces, IgG titers and neutralizing antibodies in serum. Collectively, our results suggested that recombinant B. subtilis CotGSG expressing the TGEV S protein could effectively induce immune responses via DCs and provided a perspective on potential novel strategy and approach that may be applicable to the development of the next generation of TGEV vaccines.
- Chair
Location: Melbourne, Australia
Chair
Damien John Zanker
La Trobe University, Australia
- Mucosal Vaccination