Development of a challenge-protective vaccine concept by modification of the viral RNA-dependent RNA polymerase of canine distemper virus.
J Virol
; 81(24): 13649-58, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17898047
ABSTRACT
We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a "quick response" in vaccine development against well-known and "new" viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
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RNA Polimerase Dependente de RNA
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Vacinas Atenuadas
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Vacinas Virais
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Proteínas de Fluorescência Verde
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Cinomose
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Vírus da Cinomose Canina
Limite:
Animals
Idioma:
En
Revista:
J Virol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Reino Unido