Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults.
Vaccine
; 36(5): 668-674, 2018 01 29.
Article
em En
| MEDLINE
| ID: mdl-29289383
ABSTRACT
BACKGROUND:
Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke.METHODS:
Phase 3 observer-blinded, randomized (21 HBsAg-1018 [HEPLISAV-B™]HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70â¯years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status.RESULTS:
Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (Nâ¯=â¯6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group.CONCLUSION:
Two doses of HBsAg-1018, administered over 4â¯weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24â¯weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier NCT02117934.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vacinas contra Hepatite B
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Receptor Toll-Like 9
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Imunogenicidade da Vacina
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Hepatite B
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Antígenos de Superfície da Hepatite B
Tipo de estudo:
Clinical_trials
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Guideline
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article