Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis
4 affiliations
- 1Key Laboratory of Animal Parasitology, Ministry of Agriculture/ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
- 2Huangyuan County Animal Husbandry and Veterinary Station, Xining, Qinghai Province, China.
- 3Animal Science Department, Qinghai Agricultural and Animal Husbandry Technology Vocational College, Xining, Qinghai Province, China.
- 4Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease, Yangzhou, Jiangsu Province, China.
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.
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BibTeX
@article{chen2026novel,
title = {{Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis}},
author = {Wei-Gang Chen and Li Li and Guo-Dong Dai and Yao-Dong Wu and Chuan-Gang Zhu and Huan Zhang and Xiu-Rong Li and Le Li and Nian-Zhang Zhang and Li-Qun Wang and Guo-Cai Li and Wen-Ling Ma and Ji-Tao Pan and Ming-Lu Tan and Fu-Lan Da and Hong Yin and Bao-Quan Fu and Xue-Nong Luo and Hong-Bin Yan and Wan-Zhong Jia},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014659},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014659},
note = {CC BY},
}
RIS
TY - JOUR
TI - Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis
AU - Wei-Gang Chen
AU - Li Li
AU - Guo-Dong Dai
AU - Yao-Dong Wu
AU - Chuan-Gang Zhu
AU - Huan Zhang
AU - Xiu-Rong Li
AU - Le Li
AU - Nian-Zhang Zhang
AU - Li-Qun Wang
AU - Guo-Cai Li
AU - Wen-Ling Ma
AU - Ji-Tao Pan
AU - Ming-Lu Tan
AU - Fu-Lan Da
AU - Hong Yin
AU - Bao-Quan Fu
AU - Xue-Nong Luo
AU - Hong-Bin Yan
AU - Wan-Zhong Jia
PY - 2026
DA - 2026/10/09
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014659
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014659
AB - 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.
SN - 1553-7374
SN - 1553-7366
ER -