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Biotechnology and Applied Biochemistry (2001) 33, (47–51) (Printed in Great Britain)

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Repeated administration of hepatitis C virus core-encoding plasmid to mice does not necessarily increase the immune response generated against this antigen

Santiago Dueñas-Carrera*, Liz Alvarez-Lajonchere*, Julio Cesar Alvarez*, Thelvia Ramos†, Dagmara Pichardo* and Juan Morales*

*HCV Department, Vaccine Division, Centro de Ingeniería Genética y Biotecnología, P.O. Box 6162, Havana City, Cuba, and †Centro Nacional de Genética Médica, P.O. Box 6162, Havana City, Cuba

Abbreviations used: CTL, cytotoxic-T-lymphocyte; HCV, hepatitis C virus; PBST, PBS containing 0.05% Tween 20.

¹ To whom correspondence should be addressed (e-mail juan.morales@cigb.edu.cu).

DNA immunization is a promising approach in generating immune responses to infectious pathogens in many different animal models. In an effort to augment the anti-[hepatitis C virus (HCV) core] immune response, generated after DNA immunization, the importance of vaccination regimen regarding dose and boosting was investigated in the present study. Balb/c mice were intramuscularly injected with an expression plasmid encoding a truncated variant comprising amino acids 1–176 of the HCV core protein. The highest anti-core antibody titres (1:3700) were detected in mice inoculated with 50–100 µg of core-encoding plasmid. Additionally, we demonstrated that antibody levels induced by a single injection of DNA could be further increased by boosting with a second injection of DNA three weeks after primary immunization. However, administration of additional doses or lengthening of the resting period between inoculations resulted in similar or even weaker anti-core antibody responses. A similar anti-(HCV core) lymphoproliferative response was also detected in animals that had the highest level of anti-core antibodies. These results indicate that, in clinical trials, vaccination regimen might be a critical factor in generating optimal anti-(HCV core) immune responses after genetic immunization.

Received 5 October 2000; accepted 12 December 2000

Portland Press Ltd © 2001