Tropical Medicine Commons^™

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity To Onchocerca Volvulus In Mice And Non-Human Primates, Nathan M Ryan, Jessica A Hess, Erica J Robertson, Nancy Tricoche, Cheri Turner, Jenn Davis, Nikolai Petrovsky, Melissa Ferguson, William J Rinaldi, Valerie M Wong, Ayako Shimada, Bin Zhan, Maria Elena Bottazzi, Benjamin L Makepeace, Sean A Gray, Darrick Carter, Sara Lustigman, David Abraham

Faculty, Staff and Students Publications

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for …

A Serological Assay To Detect And Differentiate Rodent Exposure To Soft Tick And Hard Tick Relapsing Fever Infections In The United States, Christina M Parise, Ying Bai, Kevin S Brandt, Shelby L Ford, Sarah Maes, Adam J Replogle, Alexander R Kneubehl, Job E Lopez, Rebecca J Eisen, Andrias Hojgaard

Faculty, Staff and Students Publications

Human cases of relapsing fever (RF) in North America are caused primarily by Borrelia hermsii and Borrelia turicatae, which are spread by argasid (soft) ticks, and by Borrelia miyamotoi, which is transmitted by ixodid (hard) ticks. In some regions of the United States, the ranges of the hard and soft tick RF species are known to overlap; in many areas, recorded ranges of RF spirochetes overlap with Lyme disease (LD) group Borrelia spirochetes. Identification of RF clusters or cases detected in unusual geographic localities might prompt public health agencies to investigate environmental exposures, enabling prevention of additional cases through locally …

Tonb-Dependent Receptor Protein Displayed On Spores Of Bacillus Subtilis Stimulates Protective Immune Responses Against Acinetobacter Baumannii, Nor-Aziyah Matrahim, Kathryn Marie Jones, Brian P Keegan, Ulrich Strych, Bin Zhan, Hai-Yen Lee, Sazaly Abubakar

Faculty, Staff and Students Publications

The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from A. baumannii were displayed on the surface of Bacillus subtilis spores. The immunogenicity of the recombinant spores was evaluated in orally vaccinated mice. None of the immunized mice demonstrated signs of illness and were observed to be healthy throughout the study. Sera and the intestinal secretions from the recombinant spores-treated mice demonstrated mucosal and humoral antibody responses …

Microbiome Alterations Driven By Trypanosoma Cruzi Infection In Two Disjunctive Murine Models, Sergio Castañeda, Marina Muñoz, Peter J Hotez, Maria Elena Bottazzi, Alberto E Paniz-Mondolfi, Kathryn M Jones, Rojelio Mejia, Cristina Poveda, Juan David Ramírez

Faculty, Staff and Students Publications

Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal …

Covid-19 Vaccines And The Pandemic: Lessons Learnt For Other Neglected Diseases And Future Threats, Peter J Hotez, Sarah Gilbert, Melanie Saville, Lois Privor-Dumm, Salim Abdool-Karim, Didi Thompson, Jean-Louis Excler, Jerome H Kim

Faculty, Staff and Students Publications

Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while …

Reconstructive Surgery For The Neglected Tropical Diseases: Global Gaps And Future Directions, Kala T Pham, Peter J Hotez, Kristy L Hamilton

Faculty, Staff and Students Publications

BACKGROUND: Several neglected tropical diseases (NTDs) are highly disfiguring, particularly those in resource-poor countries that lack access to basic surgery. There has been a push to integrate surgery into treatment programs for NTDs. In this article, we provide an overview of the major disfiguring NTDs and discuss the processes and barriers that impede access to reconstructive surgical treatments or their integration into health systems.

METHODS: A review of the literature was conducted using the online database PubMed, from 2008 to 2021 with the specific diseases listed as NTDs either on the World Health Organization or the

RESULT: Success in the …

Response To Letter From Dr Thorakkal Shamim, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

A Randomized Phase I/Ii Safety And Immunogenicity Study Of The Montanide-Adjuvanted Sars-Cov-2 Spike Protein-Rbd-Fc Vaccine, Aks-452, Eline A Feitsma, Yester F Janssen, Hendrikus H Boersma, Yannick Van Sleen, Debbie Van Baarle, David G Alleva, 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, Ari Aminetzah, Frans Sollie, Schelto Kruijff, Maarten Brom, Gooitzen M Van Dam, Todd C Zion

Faculty, Staff and Students Publications

BACKGROUND: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.

METHODS: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 - 72 years) receiving AKS-452 subcutaneously at one 90 µg …

Interleukins, Chemokines, And Tumor Necrosis Factor Superfamily Ligands In The Pathogenesis Of West Nile Virus Infection, Emna Benzarti, Kristy O Murray, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is a mosquito-borne pathogen that can lead to encephalitis and death in susceptible hosts. Cytokines play a critical role in inflammation and immunity in response to WNV infection. Murine models provide evidence that some cytokines offer protection against acute WNV infection and assist with viral clearance, while others play a multifaceted role WNV neuropathogenesis and immune-mediated tissue damage. This article aims to provide an up-to-date review of cytokine expression patterns in human and experimental animal models of WNV infections. Here, we outline the interleukins, chemokines, and tumor necrosis factor superfamily ligands associated with WNV infection and …

Confronting The Evolution And Expansion Of Anti-Vaccine Activism In The Usa In The Covid-19 Era, Richard M Carpiano, Timothy Callaghan, Renee Diresta, Noel T Brewer, Chelsea Clinton, Alison P Galvani, Rekha Lakshmanan, Wendy E Parmet, Saad B Omer, Alison M Buttenheim, Regina M Benjamin, Arthur Caplan, Jad A Elharake, Lisa C Flowers, Yvonne A Maldonado, Michelle M Mello, Douglas J Opel, Daniel A Salmon, Jason L Schwartz, Joshua M Sharfstein, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

Human Schistosomiasis Vaccines As Next Generation Control Tools, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

No abstract provided.

Case Report: Exposure To Relapsing Fever Group Borreliae In Patients With Undifferentiated Febrile Illness In Mexico, Edwin Vázquez-Guerrero, Guadalupe Gordillo-Pérez, Nora Ríos-Sarabia, Job E Lopez, J Antonio Ibarra

Faculty, Staff and Students Publications

Relapsing fever (RF) borreliosis is a neglected disease in Mexico. A retrospective serological survey using diagnostic antigens GlpQ and BipA from Borrelia turicatae was performed to evaluate human exposure to RF borreliae. Seventy serum samples were used from a cohort of patients with undifferentiated febrile illness in Mexico. Four samples were positive to GlpQ and three to BipA. Results indicate that RF borreliae continue to circulate in regions of Mexico and pose a risk to human health.

Sars-Cov-2 Variants Offer A Second Chance To Fix Vaccine Inequities, Peter J Hotez

Faculty, Staff and Students Publications

Global COVID-19 vaccine equity remains aspirational for much of the world. But the emergence of rapidly evolving SARS-CoV-2 variants provides new opportunities to correct past public policies, support local vaccine production and combat rising anti-vaccine aggression.

A Randomized, Controlled Phase 1b Trial Of The Sm-Tsp-2 Vaccine For Intestinal Schistosomiasis In Healthy Brazilian Adults Living In An Endemic Area, David J Diemert, Rodrigo Correa-Oliveira, Carlo Geraldo Fraga, Frederico Talles, Marcella Rezende Silva, Shital M Patel, Shirley Galbiati, Jessie K Kennedy, Jordan S Lundeen, Maria Flavia Gazzinelli, Guangzhao Li, Lara Hoeweler, Gregory A Deye, Maria Elena Bottazzi, Peter J Hotez, Hana M El Sahly, Wendy A Keitel, Jeffrey Bethony, Robert L Atmar

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge.

METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive …

Sars-Cov-2 Seroprevalence In Children Worldwide: A Systematic Review And Meta-Analysis, Reza Naeimi, Mahdi Sepidarkish, Abolfazl Mollalo, Hamid Parsa, Sanaz Mahjour, Fatemeh Safarpour, Mustafa Almukhtar, Amal Mechaal, Hiam Chemaitelly, Behnam Sartip, Elika Marhoommirzabak, Ali Ardekani, Peter J Hotez, Robin B Gasser, Ali Rostami

Faculty, Staff and Students Publications

BACKGROUND: The higher hospitalisation rates of those aged 0-19 years (referred to herein as 'children') observed since the emergence of the immune-evasive SARS-CoV-2 Omicron variant and subvariants, along with the persisting vaccination disparities highlighted a need for in-depth knowledge of SARS-CoV-2 sero-epidemiology in children. Here, we conducted this systematic review to assess SARS-CoV-2 seroprevalence and determinants in children worldwide.

METHODS: In this systematic review and meta-analysis study, we searched international and preprinted scientific databases from December 1, 2019 to July 10, 2022. Pooled seroprevalences were estimated according to World Health Organization (WHO) regions (at 95% confidence intervals, CIs) using random-effects …

Global Vaccinations: New Urgency To Surmount A Triple Threat Of Illness, Antiscience, And Anti-Semitism, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Swarsat Kaushik Nath, Preeti Pankajakshan, Trapti Sharma, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes …

Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao

Faculty, Staff and Students Publications

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, …

The Legacy Of The Covid-19 Pandemic For Childhood Vaccination In The Usa, Douglas J Opel, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Richard M Carpiano, Chelsea Clinton, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Peter J Hotez, Jason L Schwartz, Regina M Benjamin, Arthur Caplan, Renee Diresta, Rekha Lakshmanan, Yvonne A Maldonado, Michelle M Mello, Wendy E Parmet, Daniel A Salmon, Joshua M Sharfstein, Saad B Omer

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Biological Drivers Of Vector-Pathogen Interactions – Vol Ii, Ryan O M Rego, Job E Lopez, Alejandro Cabesas-Cruz

Faculty, Staff and Students Publications

No abstract provided.

Editorial: The Regulatory Immune System As A Target To Improve Adjuvants And Novel Vaccines, Carlos Jiménez-Cortegana, Cristina Poveda, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Regeneration From Cells To Limbs: Past, Present, And Future, Pamela Imperadore, Kathryn Maxson Jones, Jennifer R Morgan, Fabio De Sio, Frank W Stahnisch

Faculty, Staff and Students Publications

No abstract provided.

Vaxi-Dl: An Artificial Intelligence-Enabled Platform For Vaccine Development, P Preeti, Swarsat Kaushik Nath, Nevidita Arambam, Trapti Sharma, Priyanka Ray Choudhury, Alakto Choudhury, Vrinda Khanna, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Vaccine development is a complex and long process. It involves several steps, including computational studies, experimental analyses, animal model system studies, and clinical trials. This process can be accelerated by using in silico antigen screening to identify potential vaccine candidates. In this chapter, we describe a deep learning-based technique which utilizes 18 biological and 9154 physicochemical properties of proteins for finding potential vaccine candidates. Using this technique, a new web-based system, named Vaxi-DL, was developed which helped in finding new vaccine candidates from bacteria, protozoa, viruses, and fungi. Vaxi-DL is available at: https://vac.kamalrawal.in/vaxidl/ .

Protocol Of Detection Of West Nile Virus In Clinical Samples, Hephzibah Nwanosike, Freedom M Green, Kristy O Murray, Jill E Weatherhead, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

Prevalence Of Trypanosoma Cruzi, The Etiologic Agent Of Chagas Disease, Infection In Texas Skunks (Mammalia: Mephitidae), Bonnie E Gulas-Wroblewski, Rodion Gorchakov, Rebecca B Kairis, Robert C Dowler, Kristy O Murray

Faculty, Staff and Students Publications

Background:

Chagas disease is one of the world's most neglected tropical diseases, infecting over six million people across the Americas. The hemoparasite Trypanosoma cruzi is the etiological agent for the disease, circulating in domestic, peridomestic, and sylvatic transmission cycles that are maintained by triatomine vectors and a diversity of wild and synanthropic hosts. Public health and wildlife management interventions targeting the interruption of T. cruzi transmission rely on an understanding of the dynamics driving the ecology of this zoonotic pathogen. One wildlife host that purportedly plays a role in the transmission of Chagas disease within the southern United States is …

Immunomodulatory Proteins From Hookworms Reduce Cardiac Inflammation And Modulate Regulatory Responses In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Kathryn M Jones, Bin Zhan, Keenan J Ernste, Maria Jose Villar, Nalini Bisht, Duc Nguyen, Li-Yen Chang, Cristina Poveda, Gonteria J Robinson, Akshar J Trivedi, Colby J Hofferek, William K Decker, Vanaja Konduri

Faculty, Staff and Students Publications

Introduction

Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased …

Safety Procedures To Work With West Nile Virus In Biosafety Level 3 Facilities, Freedom M Green, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will …

Analysis Of Variable Major Protein Antigenic Variation In The Relapsing Fever Spirochete, Borrelia Miyamotoi, In Response To Polyclonal Antibody Selection Pressure, Robert D Gilmore, Brittany A Armstrong, Kevin S Brandt, Taylor J Van Gundy, Andrias Hojgaard, Job E Lopez, Alexander R Kneubehl

Faculty, Staff and Students Publications

Borrelia miyamotoi is a tick-transmitted spirochete that is genetically grouped with relapsing fever Borrelia and possesses multiple archived pseudogenes that encode variable major proteins (Vmps). Vmps are divided into two groups based on molecular size; variable large proteins (Vlps) and variable small proteins (Vsps). Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is the basis for immune evasion that causes relapsing fever in patients. This study focused on B. miyamotoi vmp expression when spirochetes were subjected to antibody killing selection pressure. We incubated a low passage parent …