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Mapping neutralizing epitopes and developing protective chimeric antibodies against porcine epidemic diarrhea virus infection.

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Τίτλος: Mapping neutralizing epitopes and developing protective chimeric antibodies against porcine epidemic diarrhea virus infection.
Συγγραφείς: Sun M; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Sun Y; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Ma Z; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Wang Z; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Gao Y; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Sun H; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Bai J; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China., Wang X; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: xwwang@njau.edu.cn., Jiang P; Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, China. Electronic address: jiangp@njau.edu.cn.
Πηγή: International journal of biological macromolecules [Int J Biol Macromol] 2026 Jul; Vol. 371, pp. 152954. Date of Electronic Publication: 2026 Jun 10.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: Guildford, Eng., IPC Science and Technology Press.
Ιατρικοί όροι (MeSH): Porcine epidemic diarrhea virus*/immunology , Antibodies, Neutralizing*/immunology , Coronavirus Infections*/immunology , Coronavirus Infections*/veterinary , Coronavirus Infections*/prevention & control , Coronavirus Infections*/virology , Antibodies, Viral*/immunology , Swine Diseases*/immunology , Swine Diseases*/virology , Swine Diseases*/prevention & control , Epitopes*/immunology , Epitope Mapping*, Antibodies, Monoclonal/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Animals ; Swine ; Mice ; Mice, Inbred BALB C ; Female
Περίληψη: Porcine epidemic diarrhea virus (PEDV) causes serious economic losses to the global pig industry. Although commercial vaccines remain the main preventive tool, their effectiveness is often reduced due to the emergence of variant strains and insufficient immune protection transferred from sows to piglets through milk. In this study, we developed three neutralizing monoclonal antibodies (mAbs) that target conserved parts of the virus as a potential treatment option. Using hybridoma technology, we immunized BALB/c mice with purified PEDV particles and obtained four neutralizing mAbs-1H9, 1E7, 3A9, and 1B12. Among these, mAbs 1H9, 1E7, and 3A9 showed strong neutralizing ability against both G1 and G2 types of PEDV. We found that mAb 1H9 recognizes a. epitope on the S1 part of the spike protein, which depends on three key amino acids: T516, N537, and N556. In comparison, mAbs 1E7 and 3A9 bind to two separate linear sequences, 186KNDWSRVATK195 and 755GVCKSGSIGY764, respectively. And all the four mAbs inhibit the viral entry by blocking a post-attachment step in viral entry process. To make these antibodies more suitable for use in pigs, we engineered three mouse-porcine chimeric antibodies, r1H9, r1E7 and r3A9. Among them, r1H9 exhibited the strongest protective efficacy, characterized by significant reductions in small intestinal viral loads (4-5-log decrease), fecal virus shedding (6-log decrease), and histopathological lesions compared to the control group. This finding provides critical insights for the development of mAbs-based therapies and informs the rational design of next-generation subunit vaccines against PEDV.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
Contributed Indexing: Keywords: Chimeric antibodies; Neutralizing antibodies; Porcine epidemic diarrhea virus; S1 protein
Substance Nomenclature: 0 (Antibodies, Neutralizing)
0 (Antibodies, Monoclonal)
0 (Antibodies, Viral)
0 (Epitopes)
0 (Spike Glycoprotein, Coronavirus)
Entry Date(s): Date Created: 20260610 Date Completed: 20260701 Latest Revision: 20260701
Update Code: 20260702
DOI: 10.1016/j.ijbiomac.2026.152954
PMID: 42269894
Βάση Δεδομένων: MEDLINE
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  Data: Mapping neutralizing epitopes and developing protective chimeric antibodies against porcine epidemic diarrhea virus infection.
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  Data: <searchLink fieldCode="JN" term="%227909578%22">International journal of biological macromolecules</searchLink> [Int J Biol Macromol] 2026 Jul; Vol. 371, pp. 152954. <i>Date of Electronic Publication: </i>2026 Jun 10.
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  Data: <searchLink fieldCode="MM" term="%22Porcine+epidemic+diarrhea+virus%22">Porcine epidemic diarrhea virus*</searchLink>/<searchLink fieldCode="MM" term="%22Porcine+epidemic+diarrhea+virus+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Antibodies%2C+Neutralizing%22">Antibodies, Neutralizing*</searchLink>/<searchLink fieldCode="MM" term="%22Antibodies%2C+Neutralizing+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Coronavirus+Infections%22">Coronavirus Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Coronavirus+Infections+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Coronavirus+Infections%22">Coronavirus Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Coronavirus+Infections+veterinary%22">veterinary</searchLink> <br /><searchLink fieldCode="MM" term="%22Coronavirus+Infections%22">Coronavirus Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Coronavirus+Infections+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Coronavirus+Infections%22">Coronavirus Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Coronavirus+Infections+virology%22">virology</searchLink> <br /><searchLink fieldCode="MM" term="%22Antibodies%2C+Viral%22">Antibodies, Viral*</searchLink>/<searchLink fieldCode="MM" term="%22Antibodies%2C+Viral+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Swine+Diseases%22">Swine Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Swine+Diseases+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Swine+Diseases%22">Swine Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Swine+Diseases+virology%22">virology</searchLink> <br /><searchLink fieldCode="MM" term="%22Swine+Diseases%22">Swine Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Swine+Diseases+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Epitopes%22">Epitopes*</searchLink>/<searchLink fieldCode="MM" term="%22Epitopes+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Epitope+Mapping%22">Epitope Mapping*</searchLink><br /><searchLink fieldCode="MH" term="%22Antibodies%2C+Monoclonal%22">Antibodies, Monoclonal</searchLink>/<searchLink fieldCode="MH" term="%22Antibodies%2C+Monoclonal+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Spike+Glycoprotein%2C+Coronavirus%22">Spike Glycoprotein, Coronavirus</searchLink>/<searchLink fieldCode="MH" term="%22Spike+Glycoprotein%2C+Coronavirus+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Swine%22">Swine</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+BALB+C%22">Mice, Inbred BALB C</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Porcine epidemic diarrhea virus (PEDV) causes serious economic losses to the global pig industry. Although commercial vaccines remain the main preventive tool, their effectiveness is often reduced due to the emergence of variant strains and insufficient immune protection transferred from sows to piglets through milk. In this study, we developed three neutralizing monoclonal antibodies (mAbs) that target conserved parts of the virus as a potential treatment option. Using hybridoma technology, we immunized BALB/c mice with purified PEDV particles and obtained four neutralizing mAbs-1H9, 1E7, 3A9, and 1B12. Among these, mAbs 1H9, 1E7, and 3A9 showed strong neutralizing ability against both G1 and G2 types of PEDV. We found that mAb 1H9 recognizes a. epitope on the S1 part of the spike protein, which depends on three key amino acids: T516, N537, and N556. In comparison, mAbs 1E7 and 3A9 bind to two separate linear sequences, <superscript>186</superscript>KNDWSRVATK<superscript>195</superscript> and <superscript>755</superscript>GVCKSGSIGY<superscript>764</superscript>, respectively. And all the four mAbs inhibit the viral entry by blocking a post-attachment step in viral entry process. To make these antibodies more suitable for use in pigs, we engineered three mouse-porcine chimeric antibodies, r1H9, r1E7 and r3A9. Among them, r1H9 exhibited the strongest protective efficacy, characterized by significant reductions in small intestinal viral loads (4-5-log decrease), fecal virus shedding (6-log decrease), and histopathological lesions compared to the control group. This finding provides critical insights for the development of mAbs-based therapies and informs the rational design of next-generation subunit vaccines against PEDV.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare no conflict of interest.
– Name: SubjectMinor
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  Data: <i>Keywords: </i>Chimeric antibodies; Neutralizing antibodies; Porcine epidemic diarrhea virus; S1 protein
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  Data: 0 (Antibodies, Neutralizing)<br />0 (Antibodies, Monoclonal)<br />0 (Antibodies, Viral)<br />0 (Epitopes)<br />0 (Spike Glycoprotein, Coronavirus)
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PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42269894
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        Value: 10.1016/j.ijbiomac.2026.152954
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      – Code: eng
        Text: English
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        StartPage: 152954
    Subjects:
      – SubjectFull: Antibodies, Monoclonal immunology
        Type: general
      – SubjectFull: Spike Glycoprotein, Coronavirus immunology
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Swine
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Mice, Inbred BALB C
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Porcine epidemic diarrhea virus immunology
        Type: general
      – SubjectFull: Antibodies, Neutralizing immunology
        Type: general
      – SubjectFull: Coronavirus Infections immunology
        Type: general
      – SubjectFull: Coronavirus Infections veterinary
        Type: general
      – SubjectFull: Coronavirus Infections prevention & control
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      – SubjectFull: Epitope Mapping
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      – TitleFull: Mapping neutralizing epitopes and developing protective chimeric antibodies against porcine epidemic diarrhea virus infection.
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              Text: 2026 Jul
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