New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.

<h4>Background</h4>New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated...

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Autores principales:	Teresa Rodríguez-Calvo, Samuel Ojosnegros, Marta Sanz-Ramos, Juan García-Arriaza, Cristina Escarmís, Esteban Domingo, Noemí Sevilla
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc7d2d16b7054ae9a4643a4776f2d019
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spelling	oai:doaj.org-article:fc7d2d16b7054ae9a4643a4776f2d0192021-12-02T20:22:01ZNew vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.1932-620310.1371/journal.pone.0010414https://doaj.org/article/fc7d2d16b7054ae9a4643a4776f2d0192010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20454676/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260).<h4>Principal finding</h4>Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV.<h4>Conclusions</h4>The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms.Teresa Rodríguez-CalvoSamuel OjosnegrosMarta Sanz-RamosJuan García-ArriazaCristina EscarmísEsteban DomingoNoemí SevillaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10414 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teresa Rodríguez-Calvo Samuel Ojosnegros Marta Sanz-Ramos Juan García-Arriaza Cristina Escarmís Esteban Domingo Noemí Sevilla New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
description	<h4>Background</h4>New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260).<h4>Principal finding</h4>Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV.<h4>Conclusions</h4>The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms.
format	article
author	Teresa Rodríguez-Calvo Samuel Ojosnegros Marta Sanz-Ramos Juan García-Arriaza Cristina Escarmís Esteban Domingo Noemí Sevilla
author_facet	Teresa Rodríguez-Calvo Samuel Ojosnegros Marta Sanz-Ramos Juan García-Arriaza Cristina Escarmís Esteban Domingo Noemí Sevilla
author_sort	Teresa Rodríguez-Calvo
title	New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
title_short	New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
title_full	New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
title_fullStr	New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
title_full_unstemmed	New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
title_sort	new vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fc7d2d16b7054ae9a4643a4776f2d019
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New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.

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