{ "abstract": "Cystic echinococcosis (CE), a neglected zoonotic disease caused by Echinococcus granulosus sensu lato, remains a significant public health and veterinary concern worldwide. Despite efforts to develop recombinant protein-based vaccines against EG95, a key protective antigen, existing platforms suffer from limited immunogenicity, short-lived immunity, and complex production processes. Here, we designed and evaluated three novel mRNA-LNP vaccines, including EG95 mRNA-LNP vaccine, IL-4-EG95 mRNA-LNP vaccine encoding EG95 fused with IL-4 via a flexible linker to enhance immune stimulation, and EG95-EC95 mRNA-LNP vaccine that multivalent formulation incorporating EC95 antigens from Echinococcus canadensis. The vaccine candidates were efficiently encapsulated in lipid nanoparticles and demonstrated robust target expression in vitro and in vivo. Immunization induced significantly stronger, more durable humoral and cellular immune responses compared to a commercial EG95 subunit vaccine both in mice and lambs. Notably, high levels of specific antibodies persisted for over 12 months post-vaccination. Parasites infection challenge experiments confirmed that these three mRNA-LNP vaccines, especially the IL-4-EG95 vaccine conferred superior protection, inhibited protoscolex survival and cyst growth. These results highlight the advantages of mRNA-based vaccines in safety, scalability, and flexibility over conventional approaches, offering a promising strategy for controlling E. granulosus sensu lato transmission and reducing the zoonotic burden of CE. Author summary: Echinococcus granulosus causes a severe zoonotic disease with substantial clinical and economic burdens across endemic regions. Current vaccine strategies relying on protein subunits remain limited by poor immunogenicity and short-lived protection. Here, we establish a novel mRNA-LNP platform delivering optimized EG95-based antigens that elicit balanced Th1/Th2 immunity and high-level, durable antibody responses. Our IL-4-EG95 candidate conferred advantageous protection in mice, significantly outperforming a commercial subunit vaccine. This study demonstrates the potential of mRNA-based vaccines to overcome key limitations of conventional anti-parasitic vaccines and opens a versatile path for controlling genetically diverse parasitic pathogens.", "abstract_shown": true, "affiliations": [ "Key Laboratory of Animal Parasitology, Ministry of Agriculture/ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.", "Huangyuan County Animal Husbandry and Veterinary Station, Xining, Qinghai Province, China.", "Animal Science Department, Qinghai Agricultural and Animal Husbandry Technology Vocational College, Xining, Qinghai Province, China.", "Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease, Yangzhou, Jiangsu Province, China." ], "article_type": "Research Article", "arxiv": null, "author_total": 20, "authors": [ { "name": "Wei-Gang Chen", "orcid": "0009-0009-1590-2115" }, { "name": "Li Li" }, { "name": "Guo-Dong Dai" }, { "name": "Yao-Dong Wu" }, { "affs": [ 0 ], "name": "Chuan-Gang Zhu" }, { "name": "Huan Zhang" }, { "name": "Xiu-Rong Li" }, { "name": "Le Li" }, { "name": "Nian-Zhang Zhang" }, { "name": "Li-Qun Wang" }, { "affs": [ 1 ], "name": "Guo-Cai Li" }, { "affs": [ 1 ], "name": "Wen-Ling Ma" }, { "affs": [ 1 ], "name": "Ji-Tao Pan" }, { "affs": [ 1 ], "name": "Ming-Lu Tan" }, { "affs": [ 2 ], "name": "Fu-Lan Da" }, { "affs": [ 3 ], "name": "Hong Yin" }, { "affs": [ 3 ], "name": "Bao-Quan Fu" }, { "affs": [ 3 ], "name": "Xue-Nong Luo" }, { "name": "Hong-Bin Yan" }, { "affs": [ 3 ], "name": "Wan-Zhong Jia" } ], "bibtex": "https://research.draconitic.com/paper/3hbj20x2te8dp.bib", "cited_by": 0, "doi": "10.1371/journal.ppat.1014659", "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014659", "id": "3hbj20x2te8dp", "issns": [ "1553-7374", "1553-7366" ], "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014659", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2734|Parasitic infections in humans and animals" ], [ "plos", "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Messenger RNA" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Immune response" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Vaccination and immunization/Vaccine development" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Antibodies" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Medicine and health sciences/Immunology/Vaccination and immunization/Vaccine development" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Infectious disease control/Vaccines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Infectious disease control/Vaccines/Booster doses" ], [ "plos", "/Medicine and health sciences/Pharmaceutics/Pharmaceutical processing technology/Drug delivery system preparation/Antigen encapsulation" ], [ "plos", "/Medicine and health sciences/Public and occupational health/Preventive medicine/Vaccination and immunization/Vaccine development" ] ], "openalex": "W7221115047", "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014659&type=printable", "pmcid": "PMC13674861", "pmid": "42853894", "published": "2026-10-09", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/3hbj20x2te8dp.ris", "sources": [ { "first_seen": "2026-10-30T12:17:30Z", "native_id": "10.1371/journal.ppat.1014659", "source": "plos", "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014659" }, { "first_seen": "2026-10-30T12:18:12Z", "native_id": "MED:42853894", "source": "europepmc", "url": "https://europepmc.org/article/MED/42853894" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" } ], "title": "Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis", "title_text": "Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:12Z", "url": "https://research.draconitic.com/paper/3hbj20x2te8dp", "venue": "PLOS Pathogens", "versions": [] }