Tropical Medicine Commons^™

Helminth-Infected Mozambican Children With Malaria Have Increased Anaemia, Cytokines And Helminth-Specific Antibodies, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejía, José Muñoz, Ruth Aguilar, Bin Zhan, Augusto Nhabomba, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Owing to their overlapping geographical distribution and the consequent occurrence of coinfections, several studies have evaluated the impact of helminth infections on malaria immune responses and clinical outcomes. However, little has been reported on how malaria coinfection affects anthelmintic responses in children harbouring worm infections. We therefore aimed to assess the impact of malaria coinfection on helminth-related clinical and immune outcomes in children. Here, we measured in plasma the levels of 30 cytokines, total IgE, and helminth-specific IgM, IgA, IgG, IgG1-4, and IgE antibodies to a panel of 11 helminth antigens by Luminex. Samples were obtained from 441 children aged …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

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 …

Intramuscular But Not Nebulized Administration Of A Mrna Vaccine Against Rhodococcus Equi Stimulated Humoral Immune Responses In Neonatal Foals, Rebecca M Legere, Cristina Poveda, Jeannine A Ott, Jocelyne M Bray, Emma G Villafone, Bibiana Petri Da Silveira, Susanne K Kahn, Cameron L Martin, Chiara Mancino, Francesca Taraballi, Michael F Criscitiello, Luc Berghman, Angela I Bordin, Jeroen Pollet, Noah D Cohen

Faculty, Staff and Students Publications

Objective: Design and evaluate immune responses of neonatal foals to a mRNA vaccine expressing the virulence-associated protein A (VapA) of Rhodococcus equi.

Animals: Cultured primary equine respiratory tract cells; Serum, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from 30 healthy Quarter Horse foals.

Methods: VapA expression was evaluated by western immunoblot in cultured equine bronchial cells transfected with 4 mRNA constructs encoding VapA. The mRNA construct with greatest expression was used to immunize foals at ages 2 and 21 days in 5 groups: (1) 300 μg nebulized mRNA (n = 6); (2) 600 μg nebulized mRNA (n …

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 …

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 …

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 …