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Welcome To our first Quarterly newsletter

CREATE-NEO in conjunction with the Sealy Center for Vector-borne and Zoonotic Diseases is pleased to introduce the first edition of our quarterly newsletter. Our aim for these newsletters is to create a platform to inform and update the scientific community of the events taking place in our Centers. We hope that our readers find this informative and engaging.

The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO) project provides a nimble and flexible network of surveillance sites in Central and South America coupled to cutting-edge modeling approaches in order to anticipate and counter emerging arboviruses.

The Sealy Center aims to harness, leverage, and expand the complimentary functions of the Institute for Human infections and Immunity (IHII), Center for Tropical Diseases (CTD), Center for Biodefense and Emerging Infectious Diseases (CBEID) and the Western Gulf Center of Excellence for Vector Borne Diseases (WGCVBD), to investigate vector-borne diseases internationally through basic, applied, clinical and field research, education, and service.

CREATE-NEO NETWORK

Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP) is a public tuition-free higher education institution in the city of São José do Rio Preto, Brazil, which offers courses in Nursing, Medicine and Psychology as well PhD Program in Health Science. FAMERP, is the leading biomedical research institute in the state of Sao Paulo, with particular strength in arbovirology, emerging infectious diseases and development of diagnostic assays for arboviral infections. Dr. Nogueira, the Site Leader, has been collaborating for the past 9 years with Dr. Vasilakis.

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) is a referral center for the diagnosis and treatment of infectious, parasitic and dermatological diseases, admitting in their facilities patients referred by the health network of Manaus and from the countryside of the Amazonas State, as well as from neighboring states and countries. Dr. Lacerda, the Site Leader, has been collaborating for the past 6 years with Drs. Vasilakis and Hanley and currently serves as the PI of the Brazilian component of our current NIH-funded ICIDR (Vasilakis-PI, Hanley, co-PI). CREATE-NEO will exploit both the research experience and strengths of the consortium investigators to investigate the mechanisms of arbovirus transmission between humans and wildlife in Manaus, Brazil.

Our future newsletters will detail the ongoing progress of other CREATE-NEO sites.

visit to PANAMA

Members of the CREATE-NEO team including Nikos Vasilakis (Principal Investigator), Kathryn Hanley (co-Principal Investigator), Shannan Rossi (Investigator), and Yasmeen Abu-Rezeq (Program Manager), visited Panama to meet and collaborate with colleagues at Gorgas Memorial Institute for Health Studies. The trip consisted of touring, collaborating, and interviewing the Gorgas - CREATE-NEO colleagues, and participating in the field work efforts in the Darien Peninsula of Panama. The three different teams in the Darien trip include the non-human primate team led by Dr. Blas Armien, the entomology team led by Dr. Anayansi Valderrama, and the human cohort and recruitment team led by Dr. Sandra Lopez and Jean-Paul Carrera.

"Our recent collaboration strengthens the long established strategic partnership between Gorgas and UTMB. In partnership and consultation with our Panamanian partners, we have established surveillance networks that encompass hotspots of biodiversity and human cohorts integrating appropriate modeling and machine learning techniques to predict and mitigate the threat posed by emerging and re-emerging arboviruses. We look forward expanding local capacity to detect, predict, and respond to emerging arboviruses at their point of origin, thereby maximizing the potential to avert full-blown emergence for the benefit of the citizens of Panama" - Dr. Nikos Vasilakis
Dr. Rossi and Yasmeen Abu-Rezeq interviewing Dr. Armien about his experience with the Gorgas Memorial Institute for Health Studies and his non-human primate work.

The Gorgas Memorial Institute for Health Studies is a leading medical research institution dedicated to researching diseases in the tropics and practicing preventative medicine in Panama since 1921. It is historically known and named after Dr. William Gorgas, who eradicated yellow fever in Panama and this accomplishment allowed for the construction of the Panama Canal. Today, Gorgas is known for its virology, genomics, entomology, immunology, high quality laboratories, as well as its contribution to Panamanian public health efforts.

|NON-HUMAN PRIMATE GROUP|

"it was an eye opening experience to participate in the NHP field work at gorgas because it allowed me to connect scientific theories with real-life knowledge" - Yasmeen Abu-rezeq, Create-ne0 Program manager.

A large component of the CREATE-NEO work involves the surveillance of non-human primates for emerging pathogens and diseases. The trip to Darien consisted of NHP howler monkey sampling near the forest edges for a total of 5 days. Sera samples and data obtained from each NHP are used to monitor the larger effort towards disease surveillance in the tropics.

|mOSQUITO cOLLECTION|

After collections are complete, the taxonomic identification of the mosquitos begins as seen in this picture.

The mosquito collections in the Darien peninsula consisted of setting traps at night and then collecting them early in the morning. "This is the most synchronized, efficient and effective vector collection team that I have ever had the privilege to work with. Their data will reveal both the current distribution of disease vectors in the landscape as well at the impacts of land use and land cover change on these distributions"- Dr. Kathryn Hanley

|HUMAN COHORT |

The third part of the CREATE-NEO effort is the human cohort study and surveillance investigations. The team surveyed residents in the Darien Peninsula for epidemiological data, environmental factors, as well as disease symptoms. The resident survey effort continued for 5 days as well, and is a part of a several year-long longitudinal study.

"The human cohort in Aruza has been established since 2012. Aruza is a community of around 600 inhabitants dedicated to agriculture and cattle ranching. Arbovirus outbreaks have been reported in Aruza since 2010, we have determined risk factors for these infections and discovered several new arboviruses." Jean Paul Carrera, Human Cohort Investigator.

|MEET CREATE-NEO's PILOT GRANT AWARDEES|

Dr. Aguiar conducting tick collections in the Pantanal.

Dr. Daniel Aguiar

Dr. Aguiar is a veterinarian and associate professor of the Faculty of Veterinary Medicine at UFMT since 2008. He has been conducting research and studies on infectious diseases in domestic animals and wildlife in the Pantanal, with a special interest in tick-borne infections.

Pathogen emergence is generally initiated by spillover of a pathogen from wildlife into livestock or humans, which which can be mediated by vectors such a ticks. Dr. Aguiar and Dr. Han (Cary Institute of Ecosystem studies) will utilize a novel combination of monitoring via camera traps, next generation sequencing and machine learning to reveal which tick species may facilitate spillover of key arboviruses in the Pantanal region of Brazil. Microclimate will be analyzed in conjunction with remotely sensed abiotic variables to characterize environmental predictors of transmission risk posed by ticks to domestic species in this region The study benefits CREATE-NEO by expanding capacity for investigation of tick-borne viruses.

Dr. Betania Drumond

Dr. Drumond is an assistant professor at Federal University of Minas Gerais (UFMG), Brazil. She has been working on arbovirus research in Brazil, mainly focusing on evolution, surveillance, virological and clinical aspects of arbovirus infection, including new findings on yellow fever. Dr. Drumond has published more than 60 peer-reviewed papers, including 3 with co-mentor Vasilakis, and has an h-index of 21.

Dr. Drumond along with colleagues at the Verena Consortium hypothesize that recent yellow fever outbreaks reveal a previously unappreciated level of connection, via mosquitoes, between humans and NHPs in eastern Brazil, which may lead to a spillover of additional arboviruses. Their objectives are to characterize the spatiotemporal dynamics and ecological drivers of yellow fever virus (YFV) circulation in NHPs and investigate whether Mayaro virus (MAYV) also broke out in NHPs concurrently with the YFV outbreak. They will quantify active infection or previous exposure of free-living NHPs to YFV or MAYV by RT-PCR and neutralizing antibody assays, respectively. Then they will identify the biotic and abiotic drivers of viral infection using spatiotemporal statistical models, with local environmental factors and new host-level traits as explanatory variables. The goal of the proposal is to predict the possible hosts and geographic extent of YFV and MAYV transmission and dynamics.

CREATE-NEO Publications

Into the woods: Changes in mosquito community composition and presence of key vectors at increasing distances from the urban edge in urban forest parks in Manaus, Brazil

Why Did ZIKV Perinatal Outcomes Differ in Distinct Regions of Brazil? An Exploratory Study of Two Cohorts

Re-emergence of yellow fever in the neotropics—quo vadis?

The vertical stratification of potential bridge vectors of mosquito-borne viruses in a central Amazonian forest bordering Manaus, Brazil.

Fatal Outcome of Ilheus Virus in the Cerebrospinal Fluid of a Patient Diagnosed with Encephalitis

Flavivirus Infection Associated with Cerebrovascular Events

Case study of two post vaccination SARS-CoV-2 infections with P1 variants in CoronaVac Vaccinees in Brazil

Lack of evidence of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) spillover in free-living neotropical non-human primates, Brazil

|MEET THE SEALY CENTER'S FY21 and fy22 PILOT GRANT AWARDEES|

Dr. Jere McBride - FY21 Recipient

Dr. McBride, Ph.D., is a Professor in the Departments of Pathology and Microbiology and Immunology, senior scientist in the Sealy Institute for Vaccine Sciences and member of the Institute for Human Infections and Immunity at the University of Texas Medical Branch. His research program focus is understanding molecular and cellular pathogen-host interactions involved in infection of mononuclear phagocytes and mechanisms of immunity to pathogenic obligately intracellular bacteria.

The long-term goal of Dr. McBride's project is to develop a stable and effective E. ch. multivalent subunit vaccine and to define the protective mechanisms of vaccine-induced immunity. The objective of his proposal is to evaluate protection provided by novel E. ch. subunit vaccine candidates using mRNA vaccination. His proposal hypothesizes that recently identified novel E. ch. secreted effector proteins will provide protection against challenge using mRNA vaccination approach. This investigation will generate data to support a comprehensive strategy aimed at identification of protective antigens in established in vivo models in an overall effort to establish a preclinical mRNA subunit vaccine for HME. The aim of the proposal is to evaluate high priority novel E. ch. protective proteins using mRNA vaccination.

Dr. Liu Hua - FY21 Recipient

Dr. Liu, Ph.D., is an Assistant Professor in the Departments of Ophthalmology and Visual Sciences. Her research interests are to understand the role of aging in human diseases.

Dr. Liu's previous work provided the first evidence that loss of anti-aging molecule Sirt6 results in progression of glomerular injury in the kidney and impairs corneal epithelial wound healing. Based on this information, the proposal hypothesizes that ZIKV infection induces the dysregulation of retinal progenitor cell phenotype switch and vascular development, leading to the activation of apoptotic and necroptotic pathways and subsequent neuronal and vascular degeneration. They aim to test this by using single-cell RNA sequencing technology to characterize retinal cell types in P5 and P8 retinas and test if ZIKV induces delayed or abnormal formation of retinal neurons, glia and vascular cells; and identify potential pathways leading to abnormal phenotype switch and cell death.

Dr. Bin Gong - FY21 Recipient

Dr. Gong, Ph.D., is an Associate Professor in the Department of Pathology at UTMB. He has more than 11 years of research experience involving experimental tomographic-pathologic studies of microvascular diseases with emphasis on mechanisms of integrity of endothelial junctions and extracellular matrices, as well as past research experience with cardiovascular diseases.

Dr. Gong's proposal hypothesized that domain III of West Nile virus (WNV) E protein (DIII)34enriched, antigen-presenting cell (APC)-targeted exosome (APC-DIII-Exo) will serve as a novel, effective and safe candidate for the development of vaccine against WNV. To test this hypothesis, they aim to generate a DIII-protein enriched Exo using the XStamp-CD40L lentivirus vector, to test the uptake of APC-DIII-Exos by APC cells and their underlying mechanisms and lastly, to assess the immunogenicity of APC-DIII-EXOs in vitro.

Dr. Alejandro Castellanos - FY22 Recipient

Dr. Alejandro Castellanos, Ph.D., is an Assistant Professor in the Department of Infectious Disease – Internal Medicine at UTMB. Dr. Castellanos has 15 years of experience working in molecular parasitology. During his postdoctoral training he was focused in the study of genes expressed in human epithelial primary cells (using microarrays) during Cryptosporidium infection at the laboratory of Dr. Clinton White at Baylor College of Medicine. During this period he became interested in using novel RNA interference techniques in Cryptosporidium but unfortunately this parasite lacks the necessary pathway to silence genes. To overcome this he discovered a novel method to silence genes in this parasite. He developed this invention through 2 funded pilot projects and recently received grants from the NIH and Bill and Melinda gates foundation to study gene silencing in Cryptosporidium. In the last 5 years he has also established novel models using in vitro cell culture and mice to test new drugs against Cryptosporidium. Working in collaboration with Dr. Wes Van Voorhis (University of Washington) and Dr. Karen Anderson (Yale University) he has evaluated the potency of several compounds against key enzymes of this parasite.

Cryptosporidiosis is estimated to give rise to over 100 million cases of diarrheal disease worldwide causing an estimated 750,000 per year within the U.S. To date, there is no vaccine against this infection. Dr. Castellanos’s proposal hypothesized that infection with attenuated CpNDK-Knock down will lead to protective immunity against subsequent infections. It also proposed to demonstrate the feasibility of developing and propagating a live attenuated strain. These studies will provide the basis for a full NIH proposal to develop one or more attenuated vaccines for preclinical and eventually clinical studies. have 15 years of experience working in molecular parasitology. In the last years, his laboratory has developed novel molecular approaches to identify drug targets and vaccine candidates. In this study, they will generate an attenuated Cryptosporidium to conduct vaccination studies in animal models. Their data will be useful for the development of novel vaccines against parasitic infections.

Dr. Miguel Cabada - FY22 Recipient

Dr. Miguel Cabada, MD, MSc, is an Associate Professor in the Department of Infectious Disease – Internal Medicine at UTMB. Dr. Cabada heads the University of Texas Medical Branch and Universidad Peruana Cayetano Heredia Collaborative Research Center in Cusco. The center is a training site in tropical medicine and global health for medical students and fellows. The facilities include fully equipped molecular biology, bacteriology-parasitology, and clinical laboratories. Dr. Cabada’s main research interests focus on neglected tropical disease including epidemiologic and translational research of new field applicable diagnostics for neglected parasites.

Dr. Cabada’s proposal hypothesized that emergent and re-emergent arboviruses have circulated widely between endemic areas in Peru and caused outbreaks of febrile illnesses in Cusco without being recognized. To test this hypothesis, they will evaluate serum samples from subjects with undifferentiated febrile illnesses of ≤ 5 days of duration collected for routine surveillance in Ministry of Health centers of the Cusco region between March 2020 and June 2021. Samples will be evaluated by multiplex reverse transcriptase PCR for the presence of seven arboviruses. Selected positive samples will be subjected to next generation sequencing for the identification of emerging and re-emerging viruses and phylogenetic analysis. They also aim to determine the clinical presentation and epidemiology of arboviruses causing acute undifferentiated febrile illness in the jungle of the Cusco region of Peru during the COVID-19 pandemic.

SEALY CENTER FY22 FELLOWSHIP RECIPIENTS

Divya Mirchandani

Divya is a second year PhD student in the Department of Microbiology and Immunology at UTMB. Prior to starting with graduate school, Divya acquired herx master’s degree in biotechnology from Florida Institute of Technology, and had been working as a biocontainment research associate in the World Reference Center for Emerging Viruses and Arboviruses at UTMB. She is interested in studying infectious diseases, specifically arthropod-borne viruses. Divya's current research focuses on cross-protection between flaviviruses, specifically the effect of pre-existing dengue virus immunity against yellow fever virus infection, and its impact on transmission via mosquitoes.

Nicholas Pittner

Nick is a Presidential Scholar and second-year student in the Human Pathophysiology and Translational Medicine Program at UTMB. His research focuses on the tick-borne pathogen, Ehrlichia chaffeensis, in the laboratory of Dr. Jere McBride. Specifically, Nick is investigating how the TRP120 effector protein of Ehrlichia chaffeensis mimics human ligands to hijack host signaling pathways.

SEMINAR SERIES

The Sealy Center for Vector-Borne and Zoonotic Diseases which is anchored by the NIH-funded Centers for Research in Emerging Infectious Diseases titled “The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO),” has established a virtual seminar series to raise awareness on the emergence and consequences of vector-borne and zoonotic diseases for public health. The Center’s seminar series is held every second Tuesday of the month. The seminar schedule is listed below. For additional information, please visit CREATE-NEO.

Organizers: Kathryn Hanley (khanley@nmsu.edu) | Nikos Vasilakis (nivasila@utmb.edu) 11am CST | 5pm GERMANY | Midnight SINGAPORE 11am CST

Upcoming deadlines - Create-NEO

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Created with an image by Alexas_Fotos - "barbary ape barbary macaque monkey"