Safety and efficacy of live attenuated PEDV vaccines for neonatal protection
Abstract Porcine epidemic diarrhea virus (PEDV) causes severe diarrheal disease with high mortality in neonatal piglets. To protect suckling piglets, maternal vaccination strategies that induce lactogenic immunity in sows are crucial. To develop modified live vaccine candidates, we generated recombi...
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Nature Portfolio
2025-06-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01195-w |
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| author | Wentao Li Basav N. Hangalapura Paul van den Elzen Erwin van den Born Frank J. M. van Kuppeveld Peter J. M. Rottier Berend-Jan Bosch |
| author_facet | Wentao Li Basav N. Hangalapura Paul van den Elzen Erwin van den Born Frank J. M. van Kuppeveld Peter J. M. Rottier Berend-Jan Bosch |
| author_sort | Wentao Li |
| collection | DOAJ |
| description | Abstract Porcine epidemic diarrhea virus (PEDV) causes severe diarrheal disease with high mortality in neonatal piglets. To protect suckling piglets, maternal vaccination strategies that induce lactogenic immunity in sows are crucial. To develop modified live vaccine candidates, we generated recombinant viruses with genome alterations such as deletion of the ORF3 accessory gene (ΔORF3), deletion of the N-terminal sialic acid binding domain of the spike glycoprotein (SΔN), and rearrangement of the spike, envelope, matrix and nucleocapsid genes (SEMN → ESMN) in the viral genome. These recombinant PEDVs were evaluated for their safety, virulence and immunogenicity in neonatal piglets. Piglets infected with the parental virus exhibited severe diarrhea and high mortality. Deletion of ORF3 alone did not attenuate the virus. Additional rearrangement of the gene order reduced virulence: rPEDV-ΔORF3-ESMN infection caused moderate diarrhea with a 50% mortality rate. The SΔN recombinant viruses, particularly when combined with other genome alterations, showed significantly reduced virulence, causing mild diarrhea and no mortality. These attenuated viruses retained their replicative ability in the gut and induced humoral immune responses (IgA and IgG). The rPEDV-SΔN vaccine candidate, selected for its favorable safety and immunogenicity profile, was tested in a pregnant sow vaccination and offspring challenge study for its ability to induce lactogenic immunity and confer protection to the offspring. Despite strong IgG responses, sow vaccination with rPEDV-SΔN resulted in low IgA serum levels and failed to protect piglets from virulent PEDV challenge. Our study defines key virulence factors for PEDV and illustrates the challenge of developing a live-attenuated vaccine that balances safety in neonatal piglets with sufficient replicative capacity in sows to stimulate lactogenic protective immunity. |
| format | Article |
| id | doaj-art-53a70cd6a2b44f8b95b7cdb25c3a3606 |
| institution | Matheson Library |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
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| series | npj Vaccines |
| spelling | doaj-art-53a70cd6a2b44f8b95b7cdb25c3a36062025-06-29T11:05:10ZengNature Portfolionpj Vaccines2059-01052025-06-0110111010.1038/s41541-025-01195-wSafety and efficacy of live attenuated PEDV vaccines for neonatal protectionWentao Li0Basav N. Hangalapura1Paul van den Elzen2Erwin van den Born3Frank J. M. van Kuppeveld4Peter J. M. Rottier5Berend-Jan Bosch6Virology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityMSD Animal HealthMSD Animal HealthMSD Animal HealthVirology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityVirology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityVirology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityAbstract Porcine epidemic diarrhea virus (PEDV) causes severe diarrheal disease with high mortality in neonatal piglets. To protect suckling piglets, maternal vaccination strategies that induce lactogenic immunity in sows are crucial. To develop modified live vaccine candidates, we generated recombinant viruses with genome alterations such as deletion of the ORF3 accessory gene (ΔORF3), deletion of the N-terminal sialic acid binding domain of the spike glycoprotein (SΔN), and rearrangement of the spike, envelope, matrix and nucleocapsid genes (SEMN → ESMN) in the viral genome. These recombinant PEDVs were evaluated for their safety, virulence and immunogenicity in neonatal piglets. Piglets infected with the parental virus exhibited severe diarrhea and high mortality. Deletion of ORF3 alone did not attenuate the virus. Additional rearrangement of the gene order reduced virulence: rPEDV-ΔORF3-ESMN infection caused moderate diarrhea with a 50% mortality rate. The SΔN recombinant viruses, particularly when combined with other genome alterations, showed significantly reduced virulence, causing mild diarrhea and no mortality. These attenuated viruses retained their replicative ability in the gut and induced humoral immune responses (IgA and IgG). The rPEDV-SΔN vaccine candidate, selected for its favorable safety and immunogenicity profile, was tested in a pregnant sow vaccination and offspring challenge study for its ability to induce lactogenic immunity and confer protection to the offspring. Despite strong IgG responses, sow vaccination with rPEDV-SΔN resulted in low IgA serum levels and failed to protect piglets from virulent PEDV challenge. Our study defines key virulence factors for PEDV and illustrates the challenge of developing a live-attenuated vaccine that balances safety in neonatal piglets with sufficient replicative capacity in sows to stimulate lactogenic protective immunity.https://doi.org/10.1038/s41541-025-01195-w |
| spellingShingle | Wentao Li Basav N. Hangalapura Paul van den Elzen Erwin van den Born Frank J. M. van Kuppeveld Peter J. M. Rottier Berend-Jan Bosch Safety and efficacy of live attenuated PEDV vaccines for neonatal protection npj Vaccines |
| title | Safety and efficacy of live attenuated PEDV vaccines for neonatal protection |
| title_full | Safety and efficacy of live attenuated PEDV vaccines for neonatal protection |
| title_fullStr | Safety and efficacy of live attenuated PEDV vaccines for neonatal protection |
| title_full_unstemmed | Safety and efficacy of live attenuated PEDV vaccines for neonatal protection |
| title_short | Safety and efficacy of live attenuated PEDV vaccines for neonatal protection |
| title_sort | safety and efficacy of live attenuated pedv vaccines for neonatal protection |
| url | https://doi.org/10.1038/s41541-025-01195-w |
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