Download the final conference abstracts booklet from the 2018 VASE Conference
Monday, June 11 | Tuesday June 12 | Wednesday June 13 | Thursday June 14
Monday, June 11, 2018
Time
Session
2:00pm - 6:00pm
Registration desk open
Tuesday, June 12, 2018
Speaker
7:00am - 6:00pm
7:30am - 8:30am
Breakfast
8:30am - 9:50am
Welcoming Keynote Address: Jaime Sepulveda | Expand Bio (+) New vaccines for old scourges: Shrinking the diarrhea mortality global gap by 2030
Jaime Sepulveda, MD, DSc, MPH, MSc Executive Director of Global Health Sciences, University of California San Francisco Dr. Jaime Sepulveda, the Haile T. Debas Distinguished Professor of Global Health, is the Executive Director of the University of California San Francisco (UCSF) Global Health Sciences. A member of UCSF Chancellor’s Cabinet, he leads a team of over 300 faculty and staff. Dr. Sepulveda obtained two masters and a doctoral degree from Harvard University. He received the Harvard Alumni Award of Merit (1997) and was elected to serve at the Harvard Board of Overseers (2002 to 2008). From 2007 to 2011, Dr. Sepulveda was a member of the Foundation Leadership Team at the Bill & Melinda Gates Foundation, where he contributed to increased access to vaccines and other effective health solutions in low-income countries. Dr. Sepulveda worked for over two decades in the Mexican government, including Director-General of Epidemiology, Vice-Minister of Health, Dean of the National School of Public Health, and Director of the National Institute of Health of Mexico. Dr. Sepulveda designed Mexico’s Universal Vaccination Program, achieving universal childhood immunization coverage. He also founded Mexico’s National AIDS Council. Dr. Sepulveda is an elected member of the National Academy of Medicine and of the American Academy of Arts and Sciences.
9:50am - 12:00pm
The Global Burden of Disease Moderated by Ibrahim Khalil, Institute of Health Metrics and Evaluation
Changes in incidence, etiology, and consequences of moderate-to-severe diarrhea among children under 5 years in sub-Saharan Africa: The VIDA study (GB081)
Karen Kotloff, University of Maryland School of Medicine, Baltimore, Maryland, USA
Etiology, burden, and characteristics of diarrhea in children in low-resource settings under quantitative molecular diagnostics: Results from the MAL-ED study (GB069)
James Platts-Mills, University of Virginia, Charlottesville, Virginia, USA
Coffee break
Impact of enteropathogen infection on linear growth using quantitative molecular diagnostics: Results from the MAL-ED study (GB065)
Eric Houpt, University of Virginia, Charlottesville, Virginia, USA
The unrecognized consequences of ETEC and Shigella non-fatal infections: Burden in 79 low- and lower middle-income countries (GB059)
John Anderson, Independent Consultant, Austin, Texas, USA
12:00pm - 1:00pm
Lunch break
1:00pm - 3:00pm
Workshop: Implications and measurement of herd protection (indirect effects) for enteric vaccine development Expand Description (+)
Organized and led by:
Scientists are making progress developing ETEC, Shigella, and other enteric vaccines. As vaccine developers prepare for field efficacy trials of these vaccines, they should be aware of the importance of herd protection (indirect effects) when assessing vaccine efficacy as well as the scientific approaches to measuring herd protection. In this workshop, we will define and describe what is meant by herd protection and present on the methods for measuring herd protection during efficacy trials and post-licensure studies in low- and middle-income nations. We will also review evidence on the effects of herd protection for estimating vaccine cost-effectiveness. Attendees should leave the workshop with an enhanced understanding of herd protection and implications for cost-effectiveness measures.
Workshop: Achieving mucosal protection: Possibilities and pitfalls for parenteral administration of vaccines to protect infants in low- and middle-income countries (LMICs) against enteric diseases Expand Description (+)
Enteric pathogens remain a major threat to human health, yet for many of these pathogens no licensed vaccine currently exists. Some candidate vaccines are subunit vaccines that may be effective in infants and children in LMICs if effective means could be devised to achieve mucosal protection via a parenteral route. This workshop will review immunologic mechanisms responsible for immunity at mucosal surfaces and present examples where the parenteral administration of a vaccine has been attempted in an effort to achieve mucosal protection. The presenters will form a panel to discuss the findings from their studies and related topics including the value of specific adjuvants for eliciting mucosal immunity via a parenteral route and the potential use of prime-boost strategies within the first year of life. It is expected that the discussion will address what regimens are most likely to be effective in the future use of parenterally-administered vaccines.
Workshop: How can CHIMs accelerate clinical development and policy pathways for vaccines against Shigella? Expand Description (+)
Shigella controlled human infection models (CHIMs) have been established at three US institutions allowing for the detailed study of diarrheal disease caused by Shigella sonnei and flexneri 2a. These models open new possibilities to investigate vaccine efficacy, the association and correlation of immune response with protection, and accelerate regulatory approval.In spring 2018, WHO is convening global stakeholders to explore potential routes to licensure for Shigella vaccines, within the context of considerations for policy recommendation, WHO prequalification, and uptake in low- and middle-income countries (LMICs). As part of this consultation, the role of CHIM models in accelerating licensure and vaccine introduction in LMICs will be considered. This workshop will explore the proposals emanating from this consultation, through a combination of presentations and round-table breakout discussions.
Workshop: Capturing the true burden of Shigella and ETEC: The way forward Expand Description (+)
The burden estimates of Shigella and ETEC vary among different studies, as well as among models used for producing these estimates. Understanding the real burden of these important pathogens will guide public health and policymakers to prioritize resources for accelerating interventions against these enteric Infections. In addition, long-term effects, in the form of growth faltering, cognitive impairment, and school performance, are important aspects of burden that have not been well captured. Efforts to incorporate these effects and refine their estimation, in the form of DALYs, are very important to inform the burden of diarrheal diseases and Shigella and ETEC specifically. This workshop will include a presentation about IHME modeling for diarrheal diseases, with a focus on Shigella and ETEC estimates in relation to other pathogens, including limitations, areas of improvement, and IHME plans for future Global Burden of Disease (GBD) iterations, followed by discussion around the following topics:
3:00pm - 3:20pm
3:20pm - 5:00pm
Understanding and Improving New Tools for Vaccine Development, Part 1 Moderated by A. Louis Bourgeois, PATH
Developing WHO preferred product characteristics for ETEC and Shigella vaccines (CMB083)
Birgitte Giersing, World Health Organization, Geneva, Switzerland
A novel diagnostics tool to aid surveillance and vaccine evaluation for diarrhea due to enterotoxigenic E. coli and Shigella spp. (GB054)
Subhra Chakraborty, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Protein microarray immune-profiling of human Shigella serum and ETEC fecal samples following vaccination and challenge (GEN072/GEN078)
Arlo Randall, Antigen Discovery Inc., Irvine, California, USA and Esther Ndungo, University of Maryland School of Medicine, Baltimore, Maryland, USA
New insights regarding the interplay between Shigella and human lymphocytes (GEN016)
Armelle Phalipon, Institut Pasteur, Paris, France
6:00pm - 8:00pm
Cocktail reception and attended poster session
Wednesday, June 13, 2018
7:00am - 2:00pm
Special Keynote Address: Timothy Hand | Expand Bio (+) Modeling the effects of malnutrition and dysbiosis on the efficacy of oral vaccination
Timothy Hand, PhD Assistant Professor, Department of Pediatrics and Department of Immunology, University of Pittsburgh Dr. Timothy Hand is an Assistant Professor of Pediatrics and Immunology and the Chair of the committee on Gnotobiotics at the University of Pittsburgh. Dr. Hand’s laboratory is within the R. K. Mellon Institute for Pediatric Research at the Children’s Hospital of Pittsburgh. Dr. Hand received his PhD from Yale University in Immunology and followed these studies with a productive post-doctoral fellowship at the US National Institutes of Health. Dr. Hand’s research focuses upon the interaction between the host immune system and the intestinal microbiota, with a particular focus on how this relationship is contextually shaped by diet and infection. Current laboratory focuses include studies of how the microbiota affects health issues relevant to children, such as vaccination, cystic fibrosis, necrotizing enterocolitis, and inflammatory bowel disease.
9:50am - 12:30pm
Recent Advances in Clinical Development and Evaluations Moderated by Wilbur Chen, University of Maryland School of Medicine
A Phase 1/2 trial of the oral inactivated ETEC vaccine (ETVAX; OEV-122) in descending age groups in Bangladesh (CL037)
Firdausi Qadri, icddr,b, Dhaka, Bangladesh
Mucosal immune responses to an oral inactivated ETEC vaccine (ETVAX) among descending age groups in Bangladesh (CL041)
Ann-Mari Svennerholm, University of Gothenburg, Institute of Biomedicine, Gothenburg, Sweden
Functional antibodies and cytokine responses to live oral Shigella sonnei vaccine strain WRSS1 in Bangladeshi adults and children (CL033)
Rubhana Raqib, icddr,b, Dhaka, Bangladesh
Safety and immunogenicity study of Sf2a-TT15, a synthetic carbohydrate-based conjugate vaccine against S. flexneri 2a in healthy adult volunteers (CL067)
Dani Cohen, Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel
Immune response profiles following vaccination with a Shigella bioconjugate vaccine that correlate with a reduction in shigellosis severity (CL036)
Chad Porter, Naval Medical Research Center, Silver Spring, Maryland, USA
12:30pm - 1:30pm
1:30pm - 3:30pm
Workshop: Role of antigen specific T and B cells in systemic and mucosal immune responses in ETEC and Shigella infections, and their potential to serve as correlates of protection in vaccine development Expand Description (+)
The hallmark of an optimal vaccine candidate is the generation of robust systemic and mucosal antibody and cell-mediated immune responses that are long-lasting, durable, and can be recalled upon subsequent re-exposure to the antigen. This usually entails the activation of T cell memory and effector subsets and induction of long-lasting B memory (BM) cells. However, for ETEC and Shigella, the precise role of these key immune cells in primary and secondary (anamnestic) immune responses remains ill-defined. To better elucidate the mechanistic role of T-cell subset and B-cells, both systemically and in the mucosal microenvironment, in the development of durable protective immunity against ETEC and Shigella, this workshop will be comprised of a series of short talks by experts in these areas followed by a panel discussion.
Workshop: The way forward for ETEC controlled human infection models (CHIMs) Expand Description (+)
Several ETEC CHIMs have been performed in the United States and Norway during the last several years. This workshop will follow up on central topics raised in the 2016 VASE CHIM workshop, with a specific focus on ETEC and new data obtained and analyzed since then. In light of recent studies with established ETEC challenge strains and new ST-only strains, we will discuss whether there is a need for more strains, and, if so, what criteria/qualities are desirable in strain selection. We will discuss how ETEC CHIMs could be more standardized to better support ETEC vaccine development, incorporating novel methods of inoculum preparation, the development and application of new immunological tools, and recent experience in dose responses, fasting times, and the evaluation of broader outcome measures. The use of ETEC CHIMs to evaluate vaccine efficacy requires susceptible volunteers to achieve a sufficiently high attack rate. We will highlight recent experience in evaluating pre-existing immunity and volunteer susceptibility to ETEC, and discuss how these data may be used to refine subject selection criteria while ensuring a representative study population. CHIMs can also be utilized to expand our knowledge of ETEC pathogenesis and correlates of protection. We will include a focused discussion on expanded sample collection schema and collaborative analysis plan that will facilitate a more in-depth assessment of the role of antigen-specific humoral and cellular immune responses in ETEC infection and provide better insights into how the most promising ETEC vaccine candidates may impact on both acute and potentially more long-term consequences of ETEC infections.
Workshop: Technical product attributes in development of an oral enteric vaccine for infants Expand Description (+)
Childhood vaccine schedules continue to grow more and more complex. Efforts to reduce the complexity of childhood vaccination include combining products for a single administration as well as alternative routes of administration that do not require injections. Oral vaccine administration is a particularly attractive alternative for enteric vaccine development because of this route's ability to elicit both mucosal and systemic immunity. This workshop will work to identify the key product attributes and considerations in product development from different perspectives: regulatory, manufacturing, formulation, etc.
Workshop: How genomics can be used to understand host susceptibility to enteric infection, aiding development of vaccines and immunotherapeutic interventions Expand Description (+)
Thanks to the modern sequencing era, the extent to which infectious disease imposes selective pressures on different human populations, is being revealed. This is aiding our understanding of the underlying host immunological and mechanistic defenses against these pathogens, as well as potentially assisting in the development of vaccines and therapeutics to control them. Therefore, the aim of this workshop is for key speakers from the enterotoxigenic Escherichia coli (ETEC) and Shigella field, to present examples of different techniques being used to investigate the underlying immune and biological transcriptional factors (both direct and indirect) that these important diarrheal pathogens impose. These presentations could be followed by an open debate on the best way to utilize such studies, before concluding and making key recommendations on how these studies could aid ETEC and Shigella vaccine development, while supporting the production of anti-infection therapeutics.
Workshop: Using advocacy to increase investment in enteric vaccine development Expand Description (+)
Catalyzing and sustaining momentum for long-term research investments can be a challenge, especially for a neglected issue like diarrheal disease. The success of rotavirus vaccines indicates that the pathway is not impossible, but it’s certainly more difficult for enteric pathogens (like ETEC and Shigella) that are most threatening to the health of children in low-resource areas and new vaccines that wouldn’t be for global use. How do you generate excitement and interest among donors to invest in diarrheal disease prevention through vaccines, especially during the early phases of clinical trials, when they may not even be aware that this is a major child health problem? During this workshop, PATH will share examples of advocacy tactics we’ve used during these early stages and provide hands-on training for real-life communication opportunities for scientists that could result in increased funding, including developing resonant messaging for key donor audiences and reviewing media interview best practices.
3:30pm - 3:50pm
3:50pm - 5:30pm
Understanding and Improving New Tools for Vaccine Development, Part 2 Moderated by Subhra Chakraborty, Johns Hopkins Bloomberg School of Public Health
Shigella-specific serum bactericidal and opsonophagocytic killing antibodies induced by oral S. flexneri 2a whole-cell killed and live attenuated vaccines (CL079)
Marcela Pasetti, University of Maryland School of Medicine, Baltimore, Maryland, USA
Immune response characterization after controlled infection with a lyophilized Shigella sonnei 53G (cGMP lot 1794) (CL035)
Kristen Clarkson, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Experimental oral challenge with B7A ETEC induces proliferative CD4+ T cell responses to CS6 and LT, which are associated with enhanced systemic and mucosal B cell responses (CL099)
Stefanie Trop, Henry M. Jackson Foundation, Silver Spring, Maryland, USA
A human challenge model for estimating protection induced by enterotoxigenic Escherichia coli heat-stable toxin-based vaccine candidates (PRE064/PRE066)
Sunniva Sakkestad, University of Bergen Centre for International Health, Bergen, Norway
Thursday, June 14, 2018
7:00am - 10:00am
8:00am - 9:30am
Sunrise Workshop: Clinical endpoints for efficacy studies Expand Description (+)
The use of well-established, validated and clinically meaningful primary and secondary endpoints is critical in advancing vaccines through proof of principal studies, licensure and pre-qualification. To that end, the field of vaccine development for Shigella, enterotoxigenic Escherichia coli (ETEC) as well as other enteric pathogens would benefit greatly from a focused review of clinical endpoints and the development of consensus endpoints across the field to enable study-to-study comparisons as well as comparative assessments between vaccine candidates. The objective of this workshop is to review clinical endpoints from controlled human challenge studies, field studies in naïve adult travelers and pediatric studies in low-middle income countries and to develop a consensus on clinical endpoints for future vaccine trials. Across three different study designs (CHIM, travelers’ efficacy and pediatric efficacy) there will be a review of traditional endpoints for studies of ETEC, Shigella and other enteric pathogens with a consideration of the disease parameters and spectrum of disease targeted for prevention. The implications of these endpoints on sample size requirements will also be considered. Additionally, the use of various scoring systems will be reviewed and their merits assessed as potential primary or secondary endpoints in clinical trials of vaccine efficacy. The role of subjective endpoints and individual-based assessments of disease severity in addition to (or in lieu of) objective endpoints will be considered. In addition to clinical endpoints of disease, discussions will also consider the potential for alternative endpoints focused on long-term morbidity endpoints.
9:30am - 12:30pm
Novel Approaches to Vaccine Development Moderated by Fred Cassels, PATH
MACE, multi-antigen combination enteric, vaccine for broad protection against ETEC and Shigella infection (PRE097)
Wendy Picking, University of Kansas, Lawrence, Kansas, USA
Towards bacterial glycoprotein antigens for vaccine development (PRE088)
Anders Boysen, University of Southern Denmark, Odense, Denmark
ST-secreted conjugates are non-toxic and induce ST-neutralizing antibodies in immunized mice (PRE012)
Jacob Bitoun, Tulane University School of Medicine, New Orleans, Louisiana, USA
Towards a heat-stable toxin-based subunit vaccine against enterotoxigenic E. coli (PRE052)
Ephrem Debebe Zegeye, UniResearch, Bergen, Norway
Evaluation of class 5A fimbrial adhesin-pilin fusion vaccines in Aotus nancymaae against diarrhea caused by CS14 STh+ expressing ETEC (PRE051)
Michael Prouty, Naval Medical Research Center, Silver Spring, Maryland, USA
12:30pm
Boxed lunch available for meeting attendees
Header Photo: PATH/Mike Wang