{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:27:13Z","timestamp":1777620433398,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012809","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Texas Children\u2019s Hospital Center for Vaccine Development Intramural Funds"},{"name":"Carl Stutts and Cynthia Dyer"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIAID P30AI036211"],"award-info":[{"award-number":["NIAID P30AI036211"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCI P30CA125123"],"award-info":[{"award-number":["NCI P30CA125123"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCRR S10RR024574"],"award-info":[{"award-number":["NCRR S10RR024574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The antigen <jats:italic>Na<\/jats:italic>-GST-1, expressed by the hookworm <jats:italic>Necator americanus<\/jats:italic>, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on <jats:italic>Na<\/jats:italic>-GST-1, building on the success of recombinant <jats:italic>Na<\/jats:italic>-GST-1 (r<jats:italic>Na<\/jats:italic>-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/findings<\/jats:title>\n<jats:p>By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of <jats:italic>Na<\/jats:italic>-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 r<jats:italic>Na<\/jats:italic>-GST-1. Following two immunizations, mRNA vaccines induced similar or superior levels of antigen-specific antibodies compared to r<jats:italic>Na<\/jats:italic>-GST-1. Secretory <jats:italic>Na<\/jats:italic>-GST-1 was comparable to r<jats:italic>Na<\/jats:italic>-GST1 in producing neutralizing antibodies against <jats:italic>Na<\/jats:italic>-GST-1\u2019s thiol transferase activity, while native <jats:italic>Na<\/jats:italic>-GST-1 induced a more robust CD8+ T cell response due to its intracellular accumulation. Although PM <jats:italic>Na<\/jats:italic>-GST-1 elicited one of highest titers of antigen-specific antibody and a diverse set of memory T-cell populations, it resulted in a lower ratio of neutralizing antibodies after IgG purification compared to the other vaccine candidates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/significance<\/jats:title>\n<jats:p>These findings emphasize the importance of antigen localization in tailoring immune responses and suggest that extracellular antigens are more effective for inducing humoral responses, whereas cytosolic antigen accumulation enhances MHC-1 peptide presentation. Future studies will determine if these <jats:italic>in vitro<\/jats:italic> and immunogenicity findings translate to <jats:italic>in vivo<\/jats:italic> efficacy. Altogether, mRNA vaccines offer numerous possibilities in the development of multivalent vaccines with single or multiple antigens.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012809","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T20:18:54Z","timestamp":1736540334000},"page":"e0012809","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates"],"prefix":"10.1371","volume":"19","author":[{"given":"Athos Silva","family":"De Oliveira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leroy","family":"Versteeg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neima","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh","family":"Adhikari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jose","family":"Villar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JeAnna R.","family":"Redd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hotez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-4015","authenticated-orcid":true,"given":"Jeroen","family":"Pollet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"pntd.0012809.ref001","doi-asserted-by":"crossref","first-page":"e0009908","DOI":"10.1371\/journal.pntd.0009908","article-title":"Experimental human hookworm infection: a narrative historical review.","volume":"15","author":"PR Chapman","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012809.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2016.88","article-title":"Hookworm infection.","volume":"2","author":"A Loukas","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"pntd.0012809.ref003","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1196\/annals.1425.000","article-title":"Hookworm and Poverty.","volume":"1136","author":"P Hotez","year":"2008","journal-title":"Annals of the New York Academy of Sciences"},{"key":"pntd.0012809.ref004","doi-asserted-by":"crossref","first-page":"e0006370","DOI":"10.1371\/journal.pntd.0006370","article-title":"Global \u201cworming\u201d: Climate change and its projected general impact on human helminth infections.","volume":"12","author":"AJ Blum","year":"2018","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"pntd.0012809.ref005","doi-asserted-by":"crossref","first-page":"e1621","DOI":"10.1371\/journal.pntd.0001621","article-title":"Soil-Transmitted Helminth Reinfection after Drug Treatment: A Systematic Review and Meta-Analysis.","volume":"6","author":"T-W Jia","year":"2012","journal-title":"PLOS Neglected Tropical Diseases."},{"key":"pntd.0012809.ref006","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1128\/CMR.13.2.207","article-title":"Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock.","volume":"13","author":"S Geerts","year":"2000","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0012809.ref007","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.4161\/hv.7.11.18443","article-title":"A history of hookworm vaccine development","volume":"7","author":"B Schneider","year":"2011","journal-title":"Hum Vaccin"},{"key":"pntd.0012809.ref008","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.chom.2020.01.011","article-title":"Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps.","volume":"27","author":"T Bouchery","year":"2020","journal-title":"Cell Host Microbe"},{"key":"pntd.0012809.ref009","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/infdis\/jiu451","article-title":"Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling","volume":"211","author":"L Tribolet","year":"2015","journal-title":"J Infect Dis"},{"key":"pntd.0012809.ref010","first-page":"11","article-title":"Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes.","author":"M Wiedemann","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"pntd.0012809.ref011","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s12639-016-0841-y","article-title":"Morphometric and scanning electron microscopy based identification of Ancylostoma caninum parasites in dog.","volume":"41","author":"HS Uppal","year":"2017","journal-title":"J Parasit Dis"},{"key":"pntd.0012809.ref012","first-page":"510","article-title":"Scanning electron microscopy of hookworms. 1. Adults and infective-stage larvae of Necator americanus (Stiles, 1902).","volume":"5","author":"Y Yoshida","year":"1974","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"pntd.0012809.ref013","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1086\/597048","article-title":"Proteolytic Degradation of Hemoglobin in the Intestine of the Human Hookworm Necator americanus","volume":"199","author":"N Ranjit","year":"2009","journal-title":"The Journal of Infectious Diseases"},{"key":"pntd.0012809.ref014","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1016\/S2666-5247(21)00181-6","article-title":"Global distribution of human hookworm species and differences in their morbidity effects: a systematic review","volume":"3","author":"ACA Clements","year":"2022","journal-title":"The Lancet Microbe"},{"key":"pntd.0012809.ref015","article-title":"Vaccine value profile for Hookworm","author":"KP Puchner","year":"2023","journal-title":"Vaccine"},{"key":"pntd.0012809.ref016","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S1473-3099(21)00153-5","article-title":"Vaccination of human participants with attenuated Necator americanus hookworm larvae and human challenge in Australia: a dose-finding study and randomised, placebo-controlled, phase 1 trial","volume":"21","author":"PR Chapman","year":"2021","journal-title":"The Lancet Infectious Diseases"},{"key":"pntd.0012809.ref017","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.pt.2018.07.005","article-title":"Lessons along the Critical Path: Developing Vaccines against Human Helminths","volume":"34","author":"DJ Diemert","year":"2018","journal-title":"Trends in Parasitology"},{"key":"pntd.0012809.ref018","doi-asserted-by":"crossref","first-page":"e1024","DOI":"10.1016\/S2666-5247(23)00218-5","article-title":"Protective efficacy of short-term infection with Necator americanus hookworm larvae in healthy volunteers in the Netherlands: a single-centre, placebo-controlled, randomised, controlled, phase 1 trial","volume":"4","author":"M-A Hoogerwerf","year":"2023","journal-title":"The Lancet Microbe"},{"key":"pntd.0012809.ref019","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0169-4758(87)90148-7","article-title":"Hookworm antigens: the potential for vaccination","volume":"3","author":"PJ Hotez","year":"1987","journal-title":"Parasitol Today"},{"key":"pntd.0012809.ref020","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jaci.2012.04.027","article-title":"Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths","volume":"130","author":"DJ Diemert","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"pntd.0012809.ref021","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nrmicro2438","article-title":"Developing vaccines to combat hookworm infection and intestinal schistosomiasis","volume":"8","author":"PJ Hotez","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"pntd.0012809.ref022","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1128\/IAI.00848-09","article-title":"Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus","volume":"78","author":"B Zhan","year":"2010","journal-title":"Infect Immun"},{"key":"pntd.0012809.ref023","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1080\/21645515.2015.1036207","article-title":"Expression, purification, and characterization of the Necator americanus aspartic protease-1 (Na-APR-1 (M74)) antigen, a component of the bivalent human hookworm vaccine.","volume":"11","author":"CA Seid","year":"2015","journal-title":"Hum Vaccin Immunother"},{"key":"pntd.0012809.ref024","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1472-6807-7-42","article-title":"X-ray structures of Na-GST-1 and Na-GST-2 two glutathione s-transferase from the human hookworm Necator americanus","volume":"7","author":"OA Asojo","year":"2007","journal-title":"BMC Struct Biol"},{"key":"pntd.0012809.ref025","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1096\/fj.09-131433","article-title":"An enzymatically inactivated hemoglobinase from Necator americanus induces neutralizing antibodies against multiple hookworm species and protects dogs against heterologous hookworm infection","volume":"23","author":"MS Pearson","year":"2009","journal-title":"FASEB J"},{"key":"pntd.0012809.ref026","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1473-3099(20)30288-7","article-title":"Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial","volume":"21","author":"AA Adegnika","year":"2021","journal-title":"The Lancet Infectious Diseases"},{"key":"pntd.0012809.ref027","doi-asserted-by":"crossref","first-page":"e0005574","DOI":"10.1371\/journal.pntd.0005574","article-title":"Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults","volume":"11","author":"DJ Diemert","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012809.ref028","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1016\/j.vaccine.2022.09.017","article-title":"Safety and immunogenicity of the Na-APR-1 hookworm vaccine in infection-na\u00efve adults","volume":"40","author":"DJ Diemert","year":"2022","journal-title":"Vaccine"},{"key":"pntd.0012809.ref029","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1473-3099(24)00104-X","article-title":"Safety and immunogenicity of the co-administered Na-APR-1 and Na-GST-1 hookworm vaccines in school-aged children in Gabon: a randomised, controlled, observer-blind, phase 1, dose-escalation trial","volume":"24","author":"JF Zinsou","year":"2024","journal-title":"The Lancet Infectious Diseases"},{"key":"pntd.0012809.ref030","doi-asserted-by":"crossref","first-page":"e0009732","DOI":"10.1371\/journal.pntd.0009732","article-title":"Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon.","volume":"15","author":"YD Mouwenda","year":"2021","journal-title":"PLOS Neglected Tropical Diseases."},{"key":"pntd.0012809.ref031","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.4161\/hv.28872","article-title":"Optimization and revision of the production process of the Necator americanus glutathione S-transferase 1 (Na-GST-1), the lead hookworm vaccine recombinant protein candidate.","volume":"10","author":"E Curti","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"pntd.0012809.ref032","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/14760584.2023.2217917","article-title":"From concept to delivery: a yeast-expressed recombinant protein-based COVID-19 vaccine technology suitable for global access","volume":"22","author":"PJ Hotez","year":"2023","journal-title":"Expert Rev Vaccines"},{"key":"pntd.0012809.ref033","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","article-title":"mRNA vaccines for infectious diseases: principles, delivery and clinical translation","volume":"20","author":"N Chaudhary","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"pntd.0012809.ref034","doi-asserted-by":"crossref","first-page":"6863","DOI":"10.1016\/j.vaccine.2023.09.059","article-title":"SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses","volume":"41","author":"C Mo","year":"2023","journal-title":"Vaccine"},{"key":"pntd.0012809.ref035","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41541-023-00783-y","article-title":"mRNA vaccines expressing malaria transmission-blocking antigens Pfs25 and Pfs230D1 induce a functional immune response","volume":"9","author":"PV Scaria","year":"2024","journal-title":"NPJ Vaccines"},{"key":"pntd.0012809.ref036","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/infdis\/jix592","article-title":"Modified mRNA-Based Vaccines Elicit Robust Immune Responses and Protect Guinea Pigs From Ebola Virus Disease","volume":"217","author":"M Meyer","year":"2018","journal-title":"J Infect Dis"},{"key":"pntd.0012809.ref037","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41578-021-00372-2","article-title":"Designing spatial and temporal control of vaccine responses","volume":"7","author":"GA Roth","year":"2022","journal-title":"Nat Rev Mater"},{"key":"pntd.0012809.ref038","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.01643","article-title":"Current Concepts of Antigen Cross-Presentation.","volume":"9","author":"M Embgenbroich","year":"2018","journal-title":"Frontiers in Immunology"},{"key":"pntd.0012809.ref039","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.4161\/hv.26009","article-title":"Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1).","volume":"9","author":"A Wallace","year":"2013","journal-title":"Hum Vaccin Immunother."},{"key":"pntd.0012809.ref040","doi-asserted-by":"crossref","first-page":"e1006931","DOI":"10.1371\/journal.ppat.1006931","article-title":"A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development","volume":"14","author":"T Bouchery","year":"2018","journal-title":"PLOS Pathogens"},{"key":"pntd.0012809.ref041","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.4049\/jimmunol.179.9.5886","article-title":"Essential Role of IL-21 in B Cell Activation, Expansion, and Plasma Cell Generation during CD4+ T Cell-B Cell Collaboration1","volume":"179","author":"S Kuchen","year":"2007","journal-title":"The Journal of Immunology"},{"key":"pntd.0012809.ref042","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1261\/rna.069286.118","article-title":"Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life.","volume":"25","author":"Z Trepotec","year":"2019","journal-title":"RNA"},{"key":"pntd.0012809.ref043","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nm.4356","article-title":"Elimination of large tumors in mice by mRNA-encoded bispecific antibodies","volume":"23","author":"CR Stadler","year":"2017","journal-title":"Nat Med"},{"key":"pntd.0012809.ref044","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.ymthe.2020.01.002","article-title":"Aerosol Delivery of Synthetic mRNA to Vaginal Mucosa Leads to Durable Expression of Broadly Neutralizing Antibodies against HIV","volume":"28","author":"KE Lindsay","year":"2020","journal-title":"Mol Ther"},{"key":"pntd.0012809.ref045","doi-asserted-by":"crossref","first-page":"5884","DOI":"10.1093\/nar\/gkq347","article-title":"Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation","volume":"38","author":"BR Anderson","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"pntd.0012809.ref046","volume-title":"Guide for the Care and Use of Laboratory Animals: Eighth Edition","year":"2011"},{"key":"pntd.0012809.ref047","doi-asserted-by":"crossref","first-page":"100066","DOI":"10.1016\/j.crimmu.2023.100066","article-title":"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.","volume":"4","author":"C Poveda","year":"2023","journal-title":"Curr Res Immunol"},{"key":"pntd.0012809.ref048","doi-asserted-by":"crossref","first-page":"e0005385","DOI":"10.1371\/journal.pntd.0005385","article-title":"Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1\/Alhydrogel hookworm vaccine","volume":"11","author":"JB Brelsford","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012809.ref049","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41587-021-01156-3","article-title":"SignalP 6.0 predicts all five types of signal peptides using protein language models","volume":"40","author":"F Teufel","year":"2022","journal-title":"Nat Biotechnol"},{"key":"pntd.0012809.ref050","doi-asserted-by":"crossref","first-page":"e1007273","DOI":"10.1371\/journal.ppat.1007273","article-title":"Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm","volume":"14","author":"N Briggs","year":"2018","journal-title":"PLoS Pathog"},{"key":"pntd.0012809.ref051","doi-asserted-by":"crossref","first-page":"e0005769","DOI":"10.1371\/journal.pntd.0005769","article-title":"Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response.","volume":"11","author":"J Wei","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012809.ref052","first-page":"73","article-title":"Glutathione S-transferase in helminth parasites","volume":"40","author":"N Vibanco-P\u00e9rez","year":"1998","journal-title":"Rev Latinoam Microbiol"},{"key":"pntd.0012809.ref053","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1128\/IAI.72.5.2780-2790.2004","article-title":"Binding of hematin by a new class of glutathione transferase from the blood-feeding parasitic nematode Haemonchus contortus","volume":"72","author":"AJ van Rossum","year":"2004","journal-title":"Infect Immun"},{"key":"pntd.0012809.ref054","doi-asserted-by":"crossref","first-page":"6903","DOI":"10.1128\/IAI.73.10.6903-6911.2005","article-title":"Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum","volume":"73","author":"B Zhan","year":"2005","journal-title":"Infect Immun"},{"key":"pntd.0012809.ref055","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0001-706X(95)00084-R","article-title":"Glutathione S-transferase (GST) expression in the human hookworm Necator americanus: potential roles for excretory-secretory forms of GST.","volume":"59","author":"PM Brophy","year":"1995","journal-title":"Acta Tropica"},{"key":"pntd.0012809.ref056","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1074\/mcp.M114.038950","article-title":"Secreted Proteomes of Different Developmental Stages of the Gastrointestinal Nematode Nippostrongylus brasiliensis*","volume":"13","author":"J Sotillo","year":"2014","journal-title":"Molecular & Cellular Proteomics."},{"key":"pntd.0012809.ref057","doi-asserted-by":"crossref","first-page":"e45974","DOI":"10.1371\/journal.pone.0045974","article-title":"Extracellular Vesicles from Parasitic Helminths Contain Specific Excretory\/Secretory Proteins and Are Internalized in Intestinal Host Cells.","volume":"7","author":"A Marcilla","year":"2012","journal-title":"PLOS ONE"},{"key":"pntd.0012809.ref058","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0169-4758(95)80169-3","article-title":"Offensive Secretory SODs?","volume":"11","author":"PM Brophy","year":"1995","journal-title":"Parasitology Today"},{"key":"pntd.0012809.ref059","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.immuni.2024.01.017","article-title":"SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase","volume":"57","author":"K Srivastava","year":"2024","journal-title":"Immunity"},{"key":"pntd.0012809.ref060","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41586-020-2622-0","article-title":"SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness","volume":"586","author":"KS Corbett","year":"2020","journal-title":"Nature"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0012809","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T18:37:54Z","timestamp":1737657474000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012809"}},"subtitle":[],"editor":[{"given":"Chao","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012809","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}