Induction of cytotoxic T lymphocyte responses against hepatitis delta virus antigens which protect against tumor formation in mice.

The cellular immune response is a crucial defense mechanism against hepatotropic viruses and in chronic viral hepatitis prevention. Moreover, hepatitis delta virus (HDV) immunogenicity may be an important component in the development of prophylactic and therapeutic vaccines. Therefore, we evaluated the immunogenicity of the small (HDAg) or large delta antigen (LHDAg) to be used as a DNA-based vaccine. We immunized different mouse haplotypes, determined cellular immune responses, and tested protection of animals against tumor formation using syngeneic tumor cells stably expressing the delta antigens. Both LHDAg and HDAg primed CD4+ and CD8+ T cell immunity against both forms of delta antigens. CD8+ T cell frequencies were about 1% and antigen-specific CD8+ T cells remained detectable directly ex vivo for at least 35 days post-injection. No anti-delta antibody responses could be detected despite multiple detection systems and varied immunization approaches. We observed protection against syngeneic tumor formation and growth in mice immunized with DNA plasmids encoding secreted or intracellular forms of HDAg and LHDAg but not with recombinant HDAg establishing the generation of significant cellular immunity in vivo. Both CD4+ and CD8+ T cells were required for antitumoral activity as determined by in vivo T cell depletion experiments. The results indicate that DNA-based immunization with genes encoding LHDAg and HDAg induces strong T cell responses and, therefore, is an attractive approach for the construction of therapeutic and prophylactic T cell vaccines against HDV.

[Field trial of the Cuban recombinant vaccine against hepatitis B (Heberbiovac HB). Study in newborn infants born to AgsHB+ mothers]. / Ensayo de campo de la vacuna recombinante cubana contra la hepatitis B (Heberbiovac HB). Estudio en recién nacidos hijos de madres AgsHB+.

A study was conducted on 106 newborns, whose AgsHB positive mothers received active protection against hepatitis B (83 with the Cuban-produced Heberbiovac HB vaccine and 23 with the Engerix-B vaccine manufactured by S. Kline as control group, following the scheme 0, 1 and 2 months with the first dose administered in the first 12 hours after birth. Samples were taken to study virus B markers at birth (umbilical cord) after 30, 60, 90 and 180 days. Laboratory determinations were carried out by the ELISA technique with diagnostic kits from the firm Organon Tecknica. Ten or more IU/L of anti-HBs present in serum was considered as the lowest protective level. Children were classified according to the AgeHB present in mothers, AgsHB in the umbilical cord and the concentration of Ags HB in maternal serum. 100% of the children who received the control vaccine showed serological evidence of seroconversion to anti HBs with protective titres, and the values of the geometric mean of the titres of antibodies were statistically significant (p < 0.01) in all the extractions, favoring the Cuban vaccine. The efficacy of the two preparations used in this research work was 100%. This study makes it possible to report on a recombinant vaccine against hepatitis B (Heberbiovac HB) which represents the first vaccine of this type produced in Latin America, the efficacy of which was proved in the field trial.