Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults.

A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB (®) (Heber Biotec S.A., Havana, Cuba), Euvax-B (®) (LG Chemical Ltd., Seoul, Korea), Hepavax-Gene (®)   (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B (®) (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 -  2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B (®) , Hepavax-Gene (®) , Euvax-B (®) , and Heberbiovac-HB (®) vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB (®) vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and  hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB (®) showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the  four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB (®) . [WHO primary Registry Number: RPCEC00000075].

Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial.

SUMMARY: Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals.

[Impact of an anti-hepatitis B virus (HBV) immunization program in patients undergoing dialysis in Havana, Cuba]. / Impacto del Programa de inmunización anti-virus de hepatitis B (VHB) en pacientes sometidos a diálisis en La Habana, Cuba.

The follow-up of HBV markers in selected high infection risk populations, in patients from the hemodialysis and peritoneal dialysis services was used to assess the effectiveness of a special vaccination program. Viral infection markers were studied in prevalence cross sections of the whole population of patients, and also by recording the reports of clinical cases of hepatitis B occurred during that period in those groups of patients. The prevention program consisted of the vaccination of all patients negative to the viral markers and the indication of vaccination for the new cases during the period of the kidney disease, just before the start of the treatment at the hemodialysis unit; besides all the persons susceptible to infection that had already been included in the program, regardless of the stage of the disease. The results show the benefit of the vaccination in these patients, but it is more effective in the period before the treatment with dialysis where there is a lower possibility of being exposed to the virus and the immune system is still competent. Once the program was established, after a follow up o 6 years, there have been no reports of new cases of hepatitis B and the incidence of the disease has been declining.

[A comparative study between different regimens for administering 2 doses of the Cuban anti-hepatitis B vaccine]. / Estudio comparativo entre diferentes esquemas de administración de 2 dosis con la vacuna cubana antihepatitis B.

A controlled clinical trial, corresponding to stage 2, was conducted in a population of sound adult males aged 18-23 to evaluate the immunogenicity of 5 schedules of Cuban vaccine against hepatitis B (Heberbiovac-HB [correction of Cheberbiovac-HB]). 5 groups were studied: I (control group 0, 1 and 6 months), II (0 and 2 months), III (0 and 4 months), IV (0 and 6 months), and V (0 and 8 months). The results showed no significant differences as regards the percentage of seroprotection of any of the groups of 2 doses compared with the control of 3 doses. It is concluded that between the first and the second dose there may be a period of time from 2 to 6 months with no need to reinitiate the schedule. This information will serve as a basis for a population based study to determine which schedule is the best to be used.

Safety and preliminary immunogenicity of the recombinant outer membrane protein P64k of Neisseria meningitidis in human volunteers.

P64k is a meningococcal protein from Neisseria meningitidis that has been obtained by recombinant DNA technology. Recombinant P64k has been extensively characterized by physicochemical and immunological methods. Lately this protein has been found to act as a versatile immunological carrier for weak antigens in mice. In the present work, a Phase I clinical trial was carried out in healthy volunteers who received three inoculations of either placebo or recombinant P64k (20 or 50 microg). No severe adverse events occurred during the trial. Only mild adverse events in ten volunteers were observed. At 1 month after the third dose, 15 out of 18 volunteers (83.3%) who received the recombinant antigen had a P64k-specific antibody titre > or =1:100, as detected by ELISA. A fourth dose, given 9 months after the third one, elicited a potent booster immune response in P64k vaccinees. Accordingly, these P64k formulations were considered safe and immunogenic in healthy human volunteers.