RESUMEN

BACKGROUND: Previous studies have shown that two doses of an investigational hepatitis B vaccine consisting of hepatitis B surface antigen combined with an immunostimulatory phosphorothioate oligodeoxyribonucleotide adjuvant (HBV-ISS) given 8 weeks apart provides seroprotection sooner than 3 doses of a licensed hepatitis B vaccine over 24 weeks. A more rapid schedule with a 4-week interval could provide earlier protection and potentially greater compliance. METHODS: In this randomized, double-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 or 0 and 8 weeks; saline placebo was given at week 8 for the 0-4 schedule and at week 4 for the 0-8 schedule). Adverse events were collected after each dose. Antibodies were measured at 0, 4, 8, 12, and 32 weeks. RESULTS: Participants were randomized to the 0-4 (n=18) or 0-8 (n=23) weeks schedule. Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections. By 4 weeks post-dose-2, 94.1% of 0-4 and 100% of 0-8 recipients had protective antibody levels; geometric mean concentrations were 244 mIU/mL and 3217 mIU/mL respectively. By 32 weeks, the difference in antibody concentration had decreased (GMC 439 mIU/mL vs. 863 mIU/mL, respectively; p=0.04). CONCLUSIONS: A 0-4 weeks, two-dose regimen of HBV-ISS was well-tolerated and induced an antibody response that was similar to a 0-8 weeks schedule.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Oligodesoxirribonucleótidos/administración & dosificación , Adulto , Femenino , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/química , Vacunas contra Hepatitis B/administración & dosificación , Humanos , Masculino , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/inmunología , Oligonucleótidos Fosforotioatos/administración & dosificación , Adulto Joven

RESUMEN

BACKGROUND: Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3. METHODS: Healthy, seronegative 18-28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year. RESULTS: Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87 mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B recipients had protective levels (GMC 1603 versus 2.40 mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B after both doses (74-77% compared to 34-58%; p

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Antígenos de Superficie de la Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Oligonucleótidos/administración & dosificación , Tionucleótidos/administración & dosificación , Adolescente , Adulto , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/efectos adversos , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Humanos , Masculino