Identification and validation of protective glycoproteins in Haemonchus contortus H11

Barbervax is the first and only available vaccine to protect animals against Haemonchus contortus - one of the most pathogenic parasites of small ruminants. This vaccine contains a kind of native antigen called H11, a glycoprotein complex derived from integral gut of this parasite. Native H11 has be...

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Main Authors: Hui Liu, Yao Zhang, Jiarui Li, Feng Liu, Lisha Ye, Xin Liu, Chunqun Wang, Min Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521022/full
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author Hui Liu
Yao Zhang
Jiarui Li
Feng Liu
Lisha Ye
Xin Liu
Chunqun Wang
Min Hu
author_facet Hui Liu
Yao Zhang
Jiarui Li
Feng Liu
Lisha Ye
Xin Liu
Chunqun Wang
Min Hu
author_sort Hui Liu
collection DOAJ
description Barbervax is the first and only available vaccine to protect animals against Haemonchus contortus - one of the most pathogenic parasites of small ruminants. This vaccine contains a kind of native antigen called H11, a glycoprotein complex derived from integral gut of this parasite. Native H11 has been shown to induce high levels (72-95%) of protection, but single or two recombinant molecules of H11 are consistently unsuccessful. An increasing number of aminopeptidases related to H11 have been characterized in the past three decades, but little is known about which ones are the key contributors to protective immunity. Our recent work has revealed that the immunoprotective effect of H11 is primarily associated with its N-glycan moieties. To identify key immunoprotective glycoproteins derived from H11 antigen, we employed glycan-related protective IgG antibodies combined with LC-MS/MS analysis and identified five glycosylated H11 proteins: H11, H11-1, H11-2, H11-4, and H11-5. Subsequently, we utilized the baculovirus-insect cell expression system and successfully expressed four H11 recombinant proteins including rH11, rH11-1, rH11-2 and rH11-4, which demonstrated similar aminopeptidase activity and comparable high-mannose and di-fucosylated N-glycan structures to those found on native H11. Immunization of goats with a cocktail of four rH11s induced a 66.29% reduction (p > 0.05) in total worm burden and cumulative fecal egg counts. High level of anti-rH11s IgG which could inhibit H. contortus intestinal aminopeptidase activity and larval development. Collectively, our study identified glycoprotein antigens from H11 and assessed their protective efficacy of a recombinant cocktail expressed in insect cells. This work will provide valuable insights into further development of recombinant vaccines against parasitic nematodes.
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spelling doaj-art-6edd2a552b7348c6bde91f864f8129e72025-08-20T02:04:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15210221521022Identification and validation of protective glycoproteins in Haemonchus contortus H11Hui Liu0Yao Zhang1Jiarui Li2Feng Liu3Lisha Ye4Xin Liu5Chunqun Wang6Min Hu7National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaCollege of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaBarbervax is the first and only available vaccine to protect animals against Haemonchus contortus - one of the most pathogenic parasites of small ruminants. This vaccine contains a kind of native antigen called H11, a glycoprotein complex derived from integral gut of this parasite. Native H11 has been shown to induce high levels (72-95%) of protection, but single or two recombinant molecules of H11 are consistently unsuccessful. An increasing number of aminopeptidases related to H11 have been characterized in the past three decades, but little is known about which ones are the key contributors to protective immunity. Our recent work has revealed that the immunoprotective effect of H11 is primarily associated with its N-glycan moieties. To identify key immunoprotective glycoproteins derived from H11 antigen, we employed glycan-related protective IgG antibodies combined with LC-MS/MS analysis and identified five glycosylated H11 proteins: H11, H11-1, H11-2, H11-4, and H11-5. Subsequently, we utilized the baculovirus-insect cell expression system and successfully expressed four H11 recombinant proteins including rH11, rH11-1, rH11-2 and rH11-4, which demonstrated similar aminopeptidase activity and comparable high-mannose and di-fucosylated N-glycan structures to those found on native H11. Immunization of goats with a cocktail of four rH11s induced a 66.29% reduction (p > 0.05) in total worm burden and cumulative fecal egg counts. High level of anti-rH11s IgG which could inhibit H. contortus intestinal aminopeptidase activity and larval development. Collectively, our study identified glycoprotein antigens from H11 and assessed their protective efficacy of a recombinant cocktail expressed in insect cells. This work will provide valuable insights into further development of recombinant vaccines against parasitic nematodes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521022/fullH11vaccineglycoproteinN-glycanrecombinant antigeninsect cells
spellingShingle Hui Liu
Yao Zhang
Jiarui Li
Feng Liu
Lisha Ye
Xin Liu
Chunqun Wang
Min Hu
Identification and validation of protective glycoproteins in Haemonchus contortus H11
Frontiers in Immunology
H11
vaccine
glycoprotein
N-glycan
recombinant antigen
insect cells
title Identification and validation of protective glycoproteins in Haemonchus contortus H11
title_full Identification and validation of protective glycoproteins in Haemonchus contortus H11
title_fullStr Identification and validation of protective glycoproteins in Haemonchus contortus H11
title_full_unstemmed Identification and validation of protective glycoproteins in Haemonchus contortus H11
title_short Identification and validation of protective glycoproteins in Haemonchus contortus H11
title_sort identification and validation of protective glycoproteins in haemonchus contortus h11
topic H11
vaccine
glycoprotein
N-glycan
recombinant antigen
insect cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521022/full
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