Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses.
Infect Immun
; 76(8): 3439-50, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18474644
ABSTRACT
While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes DeltaactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes DeltaactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes DeltaactA vaccine vector. Thus, recombinant attenuated L. monocytogenes DeltaactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes
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Vacunas Bacterianas
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Factores de Terminación de Péptidos
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Listeria monocytogenes
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Mutación
Límite:
Animals
Idioma:
En
Revista:
Infect Immun
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos