RESUMEN
Despite improved hepatitis C virus (HCV) treatments, vaccines remain an effective and economic option for curtailing the epidemic. Mosaic protein HCV genotype 1 vaccine candidates designed to address HCV diversity were immunogenic in mice. They elicited stronger T-cell responses to NS3-NS4a and E1-E2 proteins than did natural strains, as assessed with vaccine-matched peptides.
Asunto(s)
Hepacivirus/inmunología , Hepatitis C/inmunología , Linfocitos T/inmunología , Vacunas contra Hepatitis Viral/inmunología , Animales , Anticuerpos Antivirales/inmunología , Hepacivirus/genética , Hepatitis C/prevención & control , Ratones , Ratones Endogámicos BALB C , Vacunación , Vacunas Sintéticas , Proteínas del Envoltorio Viral/inmunología , Vacunas contra Hepatitis Viral/administración & dosificación , Vacunas contra Hepatitis Viral/genética , Proteínas no Estructurales Virales/inmunologíaRESUMEN
Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.
