Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats
Felid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- dele...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/2/163 |
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| author | Yao Lee Roger K. Maes John M. Kruger Matti Kiupel Kim S. Giessler Gisela Soboll Hussey |
| author_facet | Yao Lee Roger K. Maes John M. Kruger Matti Kiupel Kim S. Giessler Gisela Soboll Hussey |
| author_sort | Yao Lee |
| collection | DOAJ |
| description | Felid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- deletion mutants (gE-TK- and PK-) using bacterial artificial chromosome (BAC) mutagenesis and shown safety and immunogenicity in vitro. Here, we compare the safety and efficacy of a prime boost FeHV-1 gE-TK- and FeHV-1 PK- vaccination regimen with commercial vaccination in cats. Cats in the vaccination groups were vaccinated at 3-week intervals and all cats were challenge infected 3 weeks after the last vaccination. Evaluations included clinical signs, nasal shedding, virus neutralizing antibodies (VN), cytokine mRNA gene expression, post-mortem histology and detection of latency establishment. Vaccination with gE-TK- and PK- mutants was safe and resulted in significantly reduced clinical disease scores, pathological changes, viral nasal shedding, and viral DNA in the trigeminal ganglia (the site of latency) following infection. Both mutants induced VN antibodies and interferons after immunization. In addition, after challenge infection, we observed a reduction of IL-1β expression, and modulation of TNFα, TGFβ and IL10 expression. In conclusion, this study shows the merits of using FeHV-1 deletion mutants for prevention of FeHV-1 infection in cats. |
| first_indexed | 2024-03-09T03:54:54Z |
| format | Article |
| id | doaj.art-bfc2cba4693f49cb9c4c653c50d0b7f7 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:54:54Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bfc2cba4693f49cb9c4c653c50d0b7f72023-12-03T14:22:58ZengMDPI AGViruses1999-49152021-01-0113216310.3390/v13020163Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in CatsYao Lee0Roger K. Maes1John M. Kruger2Matti Kiupel3Kim S. Giessler4Gisela Soboll Hussey5Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USADepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USAFelid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- deletion mutants (gE-TK- and PK-) using bacterial artificial chromosome (BAC) mutagenesis and shown safety and immunogenicity in vitro. Here, we compare the safety and efficacy of a prime boost FeHV-1 gE-TK- and FeHV-1 PK- vaccination regimen with commercial vaccination in cats. Cats in the vaccination groups were vaccinated at 3-week intervals and all cats were challenge infected 3 weeks after the last vaccination. Evaluations included clinical signs, nasal shedding, virus neutralizing antibodies (VN), cytokine mRNA gene expression, post-mortem histology and detection of latency establishment. Vaccination with gE-TK- and PK- mutants was safe and resulted in significantly reduced clinical disease scores, pathological changes, viral nasal shedding, and viral DNA in the trigeminal ganglia (the site of latency) following infection. Both mutants induced VN antibodies and interferons after immunization. In addition, after challenge infection, we observed a reduction of IL-1β expression, and modulation of TNFα, TGFβ and IL10 expression. In conclusion, this study shows the merits of using FeHV-1 deletion mutants for prevention of FeHV-1 infection in cats.https://www.mdpi.com/1999-4915/13/2/163Felid herpesvirus-1glycoprotein E (gE)thymidine kinase (TK)serine/threonine protein kinase (PK)vaccinationcats |
| spellingShingle | Yao Lee Roger K. Maes John M. Kruger Matti Kiupel Kim S. Giessler Gisela Soboll Hussey Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats Viruses Felid herpesvirus-1 glycoprotein E (gE) thymidine kinase (TK) serine/threonine protein kinase (PK) vaccination cats |
| title | Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats |
| title_full | Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats |
| title_fullStr | Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats |
| title_full_unstemmed | Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats |
| title_short | Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats |
| title_sort | safety and efficacy of felid herpesvirus 1 deletion mutants in cats |
| topic | Felid herpesvirus-1 glycoprotein E (gE) thymidine kinase (TK) serine/threonine protein kinase (PK) vaccination cats |
| url | https://www.mdpi.com/1999-4915/13/2/163 |
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