Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model
Congenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) vaccine strategy demons...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/4/760 |
| _version_ | 1797443231660638208 |
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| author | K. Yeon Choi Nadia S. El-Hamdi Alistair McGregor |
| author_facet | K. Yeon Choi Nadia S. El-Hamdi Alistair McGregor |
| author_sort | K. Yeon Choi |
| collection | DOAJ |
| description | Congenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) vaccine strategy demonstrated complete protection against congenital GPCMV (22122 strain) and required neutralizing antibodies to various viral glycoprotein complexes. This included gB, essential for all cell types, and the pentamer complex (PC) for infection of non-fibroblast cells. All GPCMV research has utilized prototype strain 22122 limiting the translational impact, as numerous human CMV strains exist allowing re-infection and congenital CMV despite convalescent immunity. A novel GPCMV strain isolate (designated TAMYC) enabled vaccine cross strain protection studies. A GPCMV DISC (PC+) vaccine (22122 strain) induced a comprehensive immune response in animals, but vaccinated animals challenged with the TAMYC strain virus resulted in sustained viremia and the virus spread to target organs (liver, lung and spleen) with a significant viral load in the salivary glands. Protection was better than natural convalescent immunity, but the results fell short of previous DISC vaccine sterilizing immunity against the homologous 22122 virus challenge, despite a similarity in viral glycoprotein sequences between strains. The outcome suggests a limitation of the current DISC vaccine design against heterologous infection. |
| first_indexed | 2024-03-09T12:53:01Z |
| format | Article |
| id | doaj.art-85dcdb7ef6f54922bbc3ddd9272666d7 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:53:01Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-85dcdb7ef6f54922bbc3ddd9272666d72023-11-30T22:03:49ZengMDPI AGViruses1999-49152022-04-0114476010.3390/v14040760Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig ModelK. Yeon Choi0Nadia S. El-Hamdi1Alistair McGregor2Department Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX 77807, USACongenital cytomegalovirus (CMV) is a leading cause of disease in newborns and a vaccine is a high priority. The guinea pig is the only small animal model for congenital CMV but requires guinea pig cytomegalovirus (GPCMV). Previously, a disabled infectious single cycle (DISC) vaccine strategy demonstrated complete protection against congenital GPCMV (22122 strain) and required neutralizing antibodies to various viral glycoprotein complexes. This included gB, essential for all cell types, and the pentamer complex (PC) for infection of non-fibroblast cells. All GPCMV research has utilized prototype strain 22122 limiting the translational impact, as numerous human CMV strains exist allowing re-infection and congenital CMV despite convalescent immunity. A novel GPCMV strain isolate (designated TAMYC) enabled vaccine cross strain protection studies. A GPCMV DISC (PC+) vaccine (22122 strain) induced a comprehensive immune response in animals, but vaccinated animals challenged with the TAMYC strain virus resulted in sustained viremia and the virus spread to target organs (liver, lung and spleen) with a significant viral load in the salivary glands. Protection was better than natural convalescent immunity, but the results fell short of previous DISC vaccine sterilizing immunity against the homologous 22122 virus challenge, despite a similarity in viral glycoprotein sequences between strains. The outcome suggests a limitation of the current DISC vaccine design against heterologous infection.https://www.mdpi.com/1999-4915/14/4/760guinea pigcytomegalovirusglycoproteinsneutralizing antibodycongenital CMVpentamer complex |
| spellingShingle | K. Yeon Choi Nadia S. El-Hamdi Alistair McGregor Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model Viruses guinea pig cytomegalovirus glycoproteins neutralizing antibody congenital CMV pentamer complex |
| title | Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model |
| title_full | Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model |
| title_fullStr | Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model |
| title_full_unstemmed | Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model |
| title_short | Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model |
| title_sort | cross strain protection against cytomegalovirus reduces disc vaccine efficacy against cmv in the guinea pig model |
| topic | guinea pig cytomegalovirus glycoproteins neutralizing antibody congenital CMV pentamer complex |
| url | https://www.mdpi.com/1999-4915/14/4/760 |
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