RESUMEN
Although DNA vaccines have been shown to elicit potent immune responses in animal models, initial clinical trials in humans have been disappointing, highlighting a need to optimize their immunogenicity. Naked DNA vaccines are usually administered either i.m. or intradermally. The current study shows that immunization with naked DNA by direct injection into a peripheral lymph node enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically relevant CD8(+) cytotoxic T lymphocyte responses. Because injection directly into a lymph node is a rapid and easy procedure in humans, these results have important clinical implications for DNA vaccination.
Asunto(s)
Antígenos Virales/genética , ADN Viral/inmunología , Glicoproteínas/genética , Virus de la Coriomeningitis Linfocítica/genética , Fragmentos de Péptidos/genética , Vacunas de ADN/administración & dosificación , Proteínas Virales/genética , Vacunas Virales/administración & dosificación , Animales , Línea Celular , Epítopos de Linfocito T/genética , Proteínas de Homeodominio/genética , Epítopos Inmunodominantes/genética , Inyecciones Intralinfáticas/métodos , Coriomeningitis Linfocítica/prevención & control , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Plásmidos/inmunología , Linfocitos T Citotóxicos/inmunología , Vacunación , Vacunas de ADN/inmunología , Vacunas Virales/inmunologíaRESUMEN
In this study, we investigated the potential of a DNA vaccine expressing the minimal cytotoxic T lymphocyte (CTL) epitope gp33 of the lymphocytic choriomeningitis virus glycoprotein to protect against infection of a non-lymphoid organ and compared this to protection against a systemic infection. Furthermore, since immune stimulatory sequences have been shown to augment CTL responses, we examined the capacity of CpG DNA to enhance CTL memory. The data show that DNA vaccination with a gp33-based gene construct induced short-lived gp33-specific CTL which protected against a systemic infection but not against a peripheral infection. Immune stimulatory sequences were incapable of either prolonging CTL memory or promoting protection against infection of a peripheral organ.
