More than 2.7 billion people live in areas where the Zika Virus may soon spread, with potentially devastating effects for infants born in those areas. In response, faculty from across the University of Washington are working to stop the spread and effects of the Zika virus using a variety of approaches and disciplines. Here are some examples of their work, some of which is funded and some of which has not yet been funded.
Shaping the Built Environment to Control Mosquitoes
A team from the Landscape Architecture program is developing new frameworks to design the built environment for the prevention and control of mosquito-borne diseases related to Aedes aegypti and Aedes albopictus, including Zika. The project is co-led by Jorge A. Alarcón and Leann Andrews. They're doing this by:
1. Community-based design and implementation of green spaces/landscapes at homes for the prevention and control of vector-borne diseases, with a demonstration project in Iquitos, Peru.
2. Creating evidence-based design guidelines for public spaces for the prevention and control of vector-borne diseases.
3. Preliminary literature review and gap analysis of research topics related to the built environment and vector-borne diseases.
Communities Initiative: http://sqwater.be.washington.edu/wp/
Deforestation and Mosquito-borne diseases
A team of researchers at UW are developing a proposal on how deforestation in Suriname has led to a proliferation of a mosquito species that is highly effective at transmitting malaria, and that has, in some instances, replaced other less effective species that were present before the forests were cut down. This could have implications for the Zika virus, as well. Faculty include Dan Peplow, Bill Daniel, Abraham Flaxman and Amy Hagopian.
Mapping a Potential Zika Outbreak
Professor Simon Hay is a Professor of Global Health and the Director of Geospatial Science at the Institute for Health Metrics and Evaluation (IHME). His most recent study, published in eLife in April, found that a large portion of the southeastern part of our country, including much of Texas through to Florida, is highly suitable for Zika transmission. An estimated 51.8 million people in the US live in areas that are environmentally suitable for transmission of the virus, and there are 4.2 million births per year in these areas.
Improving Global Surveillance and Diagnostics: Testing the US Blood Supply with Antibodies from Parasitic Fish
Darrick Carter, with John Hansen from the USGS Fisheries Research Center and Chris Amemiya from the Benaroya Research Institute, are trying to raise money to leverage stable antibodies (VLR) from lampreys (a parasitic jawless fish) to develop a screen for the US blood supply as well as a heat-stable, deployable field test. The lampreys are used because they have an antibody-like structure, the VLR, that is extremely heat and pH stable as well as being amenable to further mutation to ensure they adhere to the Zika virus. Once developed this would allow an assessment of the danger of transmission and the current rates of contaminated units in the blood supply. Additionally, the research would produce a tool to screen samples before they are administered to high-risk patients like pregnant women.
Diagnostic Testing
UW Virology, headed by Keith Jerome, is developing diagnostic testing, including a test for the virus in serum and semen, and a Western blot to determine serostatus and differentiate Zika infections from prior exposure to dengue. They have also performed next-gen full genome sequencing on Zika isolates, and deposited to GenBank, the NIH’s open-access genetic sequence database. This will provide key data that could help researchers develop a vaccine.
Paul Yager is PI on a $19.7M multi-investigator grant from Defense Advanced Research Projects Agency (DARPA) to develop point-of-care instrument-free diagnostics devices based on rapid nucleic acid tests and paper microfluidics. In their last year of this grant they are developing a test for Zika virus in blood. Also, David Baker is PI on a proposal with Paul Yager aimed at creating a selective test for antibodies to the Zika virus.
Investigating Sexual Transmission of the Virus
Lucia Vojtech and colleagues are just beginning a project studying how Zika virus infects women when transmitted sexually. Women in all parts of the world are at risk of acquiring Zika virus from men who travel from endemic regions. In this project, they plan to study how the virus infects cells in the vagina and locally disseminates, how the presence of semen might enhance infection, and how the mucosal immune system responds. This is funded by a UW sexually transmitted infections cooperative research center developmental grant award, funded by NIH.
Understanding How the Virus Causes Inflammation and Disease to Find Treatment
Steve Polyak has gained UW’s approval to work with Zika and just completed material transfer agreements to obtain Zika virus isolates. He and his colleagues hope to have Zika virus infectivity studies going by the end of the summer. The plan is to study Zika-host cell interactions that lead to inflammation, and how to use synthetic and natural compounds as anti-inflammatory agents. Also, he is starting to apply for funding from NIH. They are also developing collaborations with colleagues in Brazil to gain access to clinical isolates of viruses as well as clinical material to study Zika-induced pathogenesis.
Minimizing the Effects of Zika on the Infant Brain
UW Medicine researcher Adams Waldorf is working with researchers in neuroscience, infectious disease, radiology and pharmacy to study the Zika virus and learn how birth defects can be prevented. Their ultimate goal is to come up with a therapeutic intervention that will minimize fetal brain injury or prevent it altogether. The team is applying for funding from the National Institutes of Health. Story: http://hsnewsbeat.uw.edu/story/researching-zika-and-birth-defects
What Makes Someone High Risk for Zika-related Microcephaly?
Drs. Romel Mackelprang and Jairam Lingappa (Department of Global Health, International Clinical Research Center) are collaborating with researchers at the University of Michigan, the University of Pittsburgh and in Recife, Brazil to apply genomic analyses to identify host genetic and viral risk factors for Zika-related microcephaly. These risk factors could help identify individuals at high risk for poor outcomes from Zika infection, and provide insights on host response pathways that could be targeted for public health prevention or clinical interventions.
Educating the Public, Health Care Providers, and Patients
The Global Center for the Integrated Health of Women, Adolescents, and Children (Global WACh), a center within the UW departments of Global Health, Obstetrics, and Pediatrics, is working with health care professionals to disseminate accurate and timely information about Zika virus to medical professionals, researchers, and to the general public. On May 6, 2016, Global WACh hosted an open panel discussion in which experts from public health, obstetrics, pediatrics, and bioengineering presented a broad range of information about Zika virus. Global WACh also maintains close collaborations with the UW Department of Bioengineering, including with Drs. Paul Yager and Barry Lutz, who are currently adapting existing diagnostic technologies to accurately detect Zika virus infection.
Since the first media reports suggesting an association between Zika virus and microcephaly, Gary Goldbaum, Director of Snohomish County Health Department, has been sending health alerts to Snohomish County’s health care providers. Assuring that the medical community is informed about communicable diseases of particular concern is a critical responsibility of the public health community and particularly of local public health agencies.
Christopher Sanford (Family Medicine, Global Health) runs a travel clinic at UW (at UW Neighborhood Northgate Clinic) and Zika is a topic he discusses in the pre-travel encounter with everyone going to Latin America, the Caribbean, or other endemic regions.
Developing a Vaccine
The Infectious Disease Research Institute (IDRI), located in Seattle, is a leader in translating research into global health solutions. At IDRI, we are developing effective and rapidly deployable vaccines for Zika Virus. We are testing multiple candidate vaccines based on different vaccine technologies, and have initiated work internally and with external industrial and non-profit partners. We have submitted multiple grants to the National Institutes of Health (NIH) to seek funding to advance this work. One Zika virus vaccine approach builds on a federally funded five-year project which has yielded an effective candidate vaccine for West Nile Virus, another virus in the same family as Zika. Following preclinical testing of our Zika virus candidate vaccines, we will leverage our ongoing partnerships with institutions and companies in Brazil and other countries around the world to clinically test the vaccine, to establish local manufacturing, and to assure that those most affected by Zika have access to a safe, protective vaccine.
Darrick Carter and colleagues are also trying to develop an RNA-based vaccine against the virus.
Mapping an Effective Vaccination Strategy
Jennifer Ross and Ruanne Barnabas are working on a mathematical modeling proposal to identify the optimal vaccination strategy to prevent the neurological sequelae of Zika virus infection. Working with collaborators in Peru they propose to document the epidemic curve of Zika virus infection and project the spread through the population. Using these empiric data and mathematical models of the Zika virus epidemic they will estimate which vaccine strategy (by gender and age) will have the largest impact on prevention of disease. This work is led by Dr. Jennifer Ross and has not been funded yet.
Tracking the Zika Virus’ Evolution
Trevor Bedford is studying the evolution of Zika virus within the Americas. His lab at the Fred Hutch is using genomic sequence data to chart the spread of the virus in the current outbreak using genetic mutations as molecular markers. He maintains an up-to-date Zika evolutionary tree at http://nextstrain.org/zika/.
Immune Response to Zika, Surpressing Infection, Developing a Vaccine
Michael Gale’s lab is working on Zika virus as follows:
- Defining the molecular processes by which Zika virus evades the immune response
- Defining the immune regulation and protection processes of the material/fetal placental interface
- Developing animal models for studies of Zika virus microcephaly and disease
They have set up a pipeline also with labs and clinical center in Brazil to expand their work.
Also, the UW Center for Innate Immunity and Immune Disease is working on Zika virus as follows:
- Making innate immune antiviral therapeutics that suppress Zika infection
- Developing a Zika virus vaccine
- Developing adjuvants for enhancing the immune response against Zika virus infection
The Seattle Structural Genomics Center for Infectious Disease (SSGCID), directed by Dr. Peter Myler at the Center for Infectious Disease Research (CID Research), is cloning and expressing the Zika virus capsid protein in order to attempt solution of the three-dimensional protein structure. The work is focused on the interaction of the capsid protein with the human protein PEX19, and will complement functional studies being performed in the lab of Dr. John Aitchison at CID Research aimed at understanding the potential role of Zika virus in peroxisome dysfunction. SSGCID is also attempting to solve the structure of four membrane-associated non-structural proteins (NS2A, NS2B, NS4A and NS4B) encoded by the Zika virus genomes, in order to gain insight into their potential function in viral pathogenesis.