Tropical Medicine Commons^™

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Measles, Mumps, Rubella Immunization And The Resurgence Of Measles In America, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A Rosa, Luke Becker, Mali Camberis, Graham Legros, Bin Zhan, Maria Elena Bottazzi, Ricardo T Fujiwara, Edita Ritmejeryte, Thewarach Laha, Sujittra Chaiyadet, Piyanan Taweethavonsawat, Paul J Brindley, Bethany K Bracken, Paul R Giacomin, Makedonka Mitreva, Alex Loukas

Faculty, Staff and Students Publications

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …

Impact Of Antiparasitic Therapy On Cardiovascular Outcomes In Chronic Chagas Disease A Systematic Review And Meta-Analysis, Anis Rassi, Alyssa Grimshaw, Ashwin Sarwal, Ranjit Sah, Sangam Shah, Nelson I Agudelo Higuita, Fabio Mahamed Rassi, Michaele Francesco Corbisiero, Hannah M Kyllo, Jordan Stellern, Samantha Kaplan, Luis A Marcos, Edgar A Ramírez-García, Martin Casapia, Peter Hotez, Maria Elena Bottazzi, Shital Patel, Carlos Franco-Paredes, José Antonio Marin-Neto, Andrés F Henao-Martínez

Faculty, Staff and Students Publications

BACKGROUND: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease.

METHODS: We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science …

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …

Use Of A Mouse Model For The Isolation Of Borrelia Puertoricensis From Soft Ticks, Edwin Vázquez-Guerrero, Alexander R Kneubehl, Guadalupe C Reyes-Solís, Carlos Machain-Williams, Aparna Krishnavajhala, Paulina Estrada-De Los Santos, Job E Lopez, José Antonio Ibarra

Faculty, Staff and Students Publications

The isolation of tick-borne relapsing fever (TBRF) spirochetes has proven to be a useful tool to understand their distribution in geographic areas where the tick vectors inhabit. However, their isolation and culture are not easy and in general an animal model is needed to achieve this task. Here, argasid ticks were collected from a neighborhood in Ciudad Caucel, and they were identified as Ornithodoros (Alectorobius) puertoricensis. To determine whether these were infected with TBRF bacteria they were fed with healthy mice but only a low burden of spirochetes was observed. An immunosuppressed mouse model was used to feed the ticks …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …

Therapeutic Effect Of Recombinant Echinococcus Granulosus Antigen B Subunit 2 Protein On Sepsis In A Mouse Model, Ya-Yun Qian, Fei-Fei Huang, Si-Yu Chen, Wei-Xiao Zhang, Yin Wang, Peng-Fei Du, Gen Li, Wen-Bo Ding, Lei Qian, Bin Zhan, Liang Chu, Dong-Hui Jiang, Xiao-Di Yang, Rui Zhou

Faculty, Staff and Students Publications

BACKGROUND: Sepsis is a potentially fatal systemic inflammatory response syndrome (SIRS) that threatens millions of lives worldwide. Echinococcus granulosus antigen B (EgAgB) is a protein released by the larvae of the tapeworm. This protein has been shown to play an important role in modulating host immune response. In this study we expressed EgAgB as soluble recombinant protein in E. coli (rEgAgB) and explored its protective effect on sepsis.

METHODS: The sepsis model was established by cecal ligation and puncture (CLP) procedure in BALB/c mice. The therapeutic effect of rEgAgB on sepsis was performed by interperitoneally injecting 5 µg rEgAgB in …

Complete Genome Sequence Of Borrelia Miyamotoi Strain Mn18-0001, An Am-East-2 Strain Type Isolate Derived From An Ixodes Scapularis Tick (Minnesota), Alexander R Kneubehl, Lynn M Osikowicz, Christina M Parise, Taylor J Van Gundy, Adam J Replogle, Job E Lopez, Rebecca J Eisen, Andrias Hojgaard

Faculty, Staff and Students Publications

We report the genomic sequence of the hard tick relapsing fever spirochete Borrelia miyamotoi strain MN18-0001. B. miyamotoi causes human illness and is geographically widespread in Ixodes spp. (Acari: Ixodidae) ticks. This is a chromosome- and plasmid-resolved genome assembly of an Am-East-2 strain type isolate from the midwestern United States.

Tick-Borne Diseases And Pregnancy: A Narrative Review Evaluating Pregnancy Complications Caused By Tick-Borne Diseases, Michael W Curtis, Job E Lopez

Faculty, Staff and Students Publications

Ticks are vectors of public health concern because the pathogens they transmit can cause detrimental diseases in humans. Lyme disease, tick-borne relapsing fever, human granulocytic anaplasmosis, Rocky Mountain spotted fever, tick-borne encephalitis, Crimean-Congo hemorrhagic fever, and babesiosis are some of the most common diseases caused by the pathogens transmitted by ticks. The overlap between human activities and tick habitats is growing, contributing to an increase in tick-borne disease cases. Unfortunately, pregnancy as a risk factor for tick-borne diseases is largely ignored. In this narrative review we use case reports, epidemiological studies, and animal studies to evaluate the maternal, pregnancy, and …

Optimization Of Cellular Transduction By The Hiv-Based Pseudovirus Platform With Pan-Coronavirus Spike Proteins, Syamala Rani Thimmiraju, Maria Jose Villar, Jason T Kimata, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has …

Treatments And The Perspectives Of Developing A Vaccine For Chagas Disease, Priscila Silva Grijó Farani, Kathryn Marie Jones, Cristina Poveda

Faculty, Staff and Students Publications

Chagas disease (CD) treatment and vaccine development are critical due to the significant health burden caused by the disease, especially in Latin America. Current treatments include benznidazole and nifurtimox, which are most effective in the acute phase of the disease but less so in the chronic phase, often with significant side effects. Here, using the available literature, we summarize the progress in vaccine development and new treatments that promise to reduce CD incidence and improve the quality of life for those at risk, particularly in endemic regions. New treatment options, such as posaconazole and fexinidazole, are being explored to improve …

A Trivalent Protein-Based Pan-Betacoronavirus Vaccine Elicits Cross-Neutralizing Antibodies Against A Panel Of Coronavirus Pseudoviruses, Syamala Rani Thimmiraju, Rakesh Adhikari, Jeanna R Redd, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Yi-Lin Chen, Suman Sharma, Amandeep Kaur, Nestor L Uzcategui, Shannon E Ronca, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

Seroprevalence Of Anti-Sars-Cov-2 Igg Antibodies In Healthcare Personnel In El Salvador Prior To Vaccination Campaigns, José Elías Aguilar Ramírez, Adrianna Maliga, Allison Stewart, Allison Lino, José Eduardo Oliva, Xochitl Sandoval, Emily Zielinski-Gutierrez, Rafael Chacon-Fuentes, Parminder S Suchdev, Susana Zelaya, Mario Sánchez, Delmy Lisseth Recinos, Beatriz López, Ella Hawes, Julie Liu, Shannon E Ronca, Sarah M Gunter, Kristy O Murray, Rhina Domínguez

Faculty, Staff and Students Publications

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike …

Water, Sanitation, And Hygiene Infrastructure And Resources In Schools In Belize During The Covid-19 Pandemic, 2021-2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Dian Maheia, Yolanda Gongora, Alexandra Medley, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Allison Lino, Vickie Romero, Rosalva Blanco, Kanako Ishida, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Access to water, sanitation, and hygiene (WASH) resources in schools is critical for disease prevention and control, especially during public health emergencies. In Belize, systematic, national data on WASH in schools are needed to inform public health decisions and interventions. From December 2021 to January 2022, a national survey was sent electronically to government and government-aided primary and secondary schools in Belize (N = 308) to gather information on WASH services. From the survey, 12 pilot schools were selected based on the highest self-reported need for WASH resources to participate in additional evaluation and intervention, which included environmental nudges, supplemental …

A Journey In Science: Molecular Vaccines For Global Child Health In Troubled Times Of Anti-Science, Peter J Hotez

Faculty, Staff and Students Publications

My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for parasitic and neglected tropical diseases, as well as pandemic threats. This includes a vaccine for human hookworm infection that I began as an MD-PhD student in New York City in the 1980s, and a new low-cost COVID vaccine that reached almost 100 million people in low- and middle-income countries. Alongside this life in scientific research, is one in public engagement for vaccine and neglected disease diplomacy to ensure that people who live in extreme poverty can …

Immunogenicity Phase Ii Study Evaluating Booster Capacity Of Nonadjuvanted Aks-452 Sars-Cov-2 Rbd Fc Vaccine, David G Alleva, Eline A Feitsma, Yester F Janssen, Hendrikus H Boersma, Thomas M Lancaster, Thillainaygam Sathiyaseelan, Sylaja Murikipudi, Andrea R Delpero, Melanie M Scully, Ramya Ragupathy, Sravya Kotha, Jeffrey R Haworth, Nishit J Shah, Vidhya Rao, Shashikant Nagre, Shannon E Ronca, Freedom M Green, Stephen A Shaw, Ari Aminetzah, Schelto Kruijff, Maarten Brom, Gooitzen M Van Dam, Todd C Zion

Faculty, Staff and Students Publications

AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60-68% responded to AKS-452 …

The Potential Epidemiologic, Clinical, And Economic Value Of A Universal Coronavirus Vaccine: A Modelling Study, Sarah M Bartsch, Kelly J O'Shea, Danielle C John, Ulrich Strych, Maria Elena Bottazzi, Marie F Martinez, Allan Ciciriello, Kevin L Chin, Colleen Weatherwax, Kavya Velmurugan, Jessie Heneghan, Sheryl A Scannell, Peter J Hotez, Bruce Y Lee

Faculty, Staff and Students Publications

BACKGROUND: With efforts underway to develop a universal coronavirus vaccine, otherwise known as a pan-coronavirus vaccine, this is the time to offer potential funders, researchers, and manufacturers guidance on the potential value of such a vaccine and how this value may change with differing vaccine and vaccination characteristics.

METHODS: Using a computational model representing the United States (U.S.) population, the spread of SARS-CoV-2 and the various clinical and economic outcomes of COVID-19 such as hospitalisations, deaths, quality-adjusted life years (QALYs) lost, productivity losses, direct medical costs, and total societal costs, we explored the impact of a universal vaccine under different …

Proteome Analysis For Inflammation Related To Acute And Convalescent Infection, Tara K Sigdel, Swastika Sur, Patrick Boada, Suzanne M Mcdermott, Cecilia S Lindestam Arlehamn, Kristy O Murray, Linda K Bockenstedt, Maggie Kerwin, Elaine F Reed, Eva Harris, Ken Stuart, Bjoern Peters, Ana Sesma, Ruth R Montgomery, Minnie M Sarwal

Faculty, Staff and Students Publications

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as …

Virology-The Path Forward, Angela L Rasmussen, Gigi K Gronvall, Anice C Lowen, Felicia Goodrum, James Alwine, Kristian G Andersen, Simon J Anthony, Joel Baines, Arinjay Banerjee, Andrew J Broadbent, Christopher B Brooke, Samuel K Campos, Patrizia Caposio, Arturo Casadevall, Gary C Chan, Anna R Cliffe, Donna Collins-Mcmillen, Nancy Connell, Blossom Damania, Matthew D Daugherty, Kari Debbink, Terence S Dermody, Daniel Dimaio, W Paul Duprex, Michael Emerman, Denise A Galloway, Robert F Garry, Stephen A Goldstein, Alexander L Greninger, Amy L Hartman, Brenda G Hogue, Stacy M Horner, Peter J Hotez, Jae U Jung, Jeremy P Kamil, Stephanie M Karst, Lou Laimins, Seema S Lakdawala, Igor Landais, Michael Letko, Brett Lindenbach, Shan-Lu Liu, Micah Luftig, Grant Mcfadden, Andrew Mehle, Juliet Morrison, Anne Moscona, Elke Mühlberger, Joshua Munger, Karl Münger, Eain Murphy, Christopher J Neufeldt, Janko Z Nikolich, Christine M O'Connor, Andrew Pekosz, Sallie R Permar, Julie K Pfeiffer, Saskia V Popescu, John G Purdy, Vincent R Racaniello, Charles M Rice, Jonathan A Runstadler, Martin J Sapp, Rona S Scott, Gregory A Smith, Erin M Sorrell, Emily Speranza, Daniel Streblow, Scott A Tibbetts, Zsolt Toth, Koenraad Van Doorslaer, Susan R Weiss, Elizabeth A White, Timothy M White, Christiane E Wobus, Michael Worobey, Satoko Yamaoka, Andrew Yurochko

Faculty, Staff and Students Publications

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is …

Novel Species Of Triatoma (Hemiptera: Reduviidae) Identified In A Case Of Vectorial Transmission Of Chagas Disease In Northern Belize, Sarah M Gunter, Alisa Nelson, Alexander R Kneubehl, Silvia A Justi, Russell Manzanero, Emily Zielinski-Gutierrez, Claudia Herrera, Julie Thompson, Rajendra Mandage, Hans Desale, Adrianna Maliga, Kim Bautista, Shannon E Ronca, Francis Morey, Rafael Chacon Fuentes, Beatriz Lopez, Eric Dumonteil, Gerhaldine H Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel …

Crystal Structure Of Trichinella Spiralis Calreticulin And The Structural Basis Of Its Complement Evasion Mechanism Involving C1q, Zhihui Jia, Wen Yu, Jingmo Li, Mingming Zhang, Bin Zhan, Liming Yan, Zhenhua Ming, Yuli Cheng, Xiaolin Tian, Shuai Shao, Jingjing Huang, Xinping Zhu

Faculty, Staff and Students Publications

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT …

Optimizing Immunogenicity And Product Presentation Of A Sars-Cov-2 Subunit Vaccine Composition: Effects Of Delivery Route, Heterologous Regimens With Self-Amplifying Rna Vaccines, And Lyophilization, William R Lykins, Jeroen Pollet, Jessica A White, Brian Keegan, Leroy Versteeg, Ulrich Strych, Wen-Hsiang Chen, Raodoh Mohamath, Gabi Ramer-Denisoff, Sierra Reed, Christina Renshaw, Samuel Beaver, Alana Gerhardt, Emily A Voigt, Mark A Tomai, Robert Sitrin, Robert K M Choy, Frederick J Cassels, Peter J Hotez, Maria Elena Bottazzi, Christopher B Fox

Faculty, Staff and Students Publications

INTRODUCTION: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.) route has been shown to improve protective mucosal responses in comparison to intramuscular (i.m.) delivery. As we gain knowledge of the limitations of existing vaccines, it is of interest to understand if changes in product presentation or combinations of multiple vaccine modalities can further improve immunological outcomes.

METHODS: We investigated a commercial-stage SARS-CoV-2 receptor binding domain (RBD) antigen adjuvanted with a clinical-stage TLR-7/8 agonist …

Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery

Faculty, Staff and Students Publications

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell …

Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model.

METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by …

Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez

Faculty, Staff and Students Publications

Ornithodoros turicata is a vector of relapsing fever spirochetes in North America and transmits Borrelia turicatae to a variety of vertebrate hosts. The remarkably long lifespan of O. turicata and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of B. turicatae in nature. Nevertheless, the reproductive biology of O. turicata is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs …

The Impact Of Vaccine-Linked Chemotherapy On Liver Health In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Duc Minh Nguyen, Cristina Poveda, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez, Kathryn Marie Jones

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. …

Localized Cardiac Small Molecule Trajectories And Persistent Chemical Sequelae In Experimental Chagas Disease, Zongyuan Liu, Rebecca Ulrich Vonbargen, April L Kendricks, Kate Wheeler, Ana Carolina Leão, Krithivasan Sankaranarayanan, Danya A Dean, Shelley S Kane, Ekram Hossain, Jeroen Pollet, Maria Elena Bottazzi, Peter J Hotez, Kathryn M Jones, Laura-Isobel Mccall

Faculty, Staff and Students Publications

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, …

Excretory/Secretory Products From Trichinella Spiralis Adult Worms Ameliorate Myocardial Infarction By Inducing M2 Macrophage Polarization In A Mouse Model, Lingqin Wu, Wenhui Yin, Jutai Wen, Shuying Wang, Huihui Li, Xiaoli Wang, Weixiao Zhang, Shuyao Duan, Qiuyu Zhu, Erhe Gao, Shili Wu, Bin Zhan, Rui Zhou, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment.

METHODS: The MI model was established by the ligation of the left anterior descending coronary artery, …