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Vaccine. 2018 May 3;36(19):2604-2611. doi: 10.1016/j.vaccine.2018.03.067. Epub 2018 Apr 5.

Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults.

Author information

1
Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States.
2
University of Texas-Southwestern Medical Center, 5939 Harry Hines Blvd #935, Dallas, TX 75235, United States.
3
Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: sjackson@alkahest.com.
4
Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: rjanssen@dynavax.com.

Abstract

BACKGROUND:

Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV-B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine.

METHODS:

A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24.

RESULTS:

Post-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups.

CONCLUSION:

HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.

KEYWORDS:

Hepatitis B vaccine; NCT00435812; NCT01005407; NCT02117934; Safety; Toll-like receptor 9

PMID:
29628151
DOI:
10.1016/j.vaccine.2018.03.067
[Indexed for MEDLINE]
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