RESUMEN

Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses.

Asunto(s)

Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Hepacivirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Anticuerpos Neutralizantes/biosíntesis , Línea Celular , Reacciones Cruzadas , Mapeo Epitopo , Epítopos/inmunología , Genotipo , Hepacivirus/genética , Hepacivirus/fisiología , Humanos , Inmunogenicidad Vacunal , Ratones , Pruebas de Neutralización , Receptores Virales/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología , Tetraspanina 28/metabolismo , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Internalización del Virus