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Development of the CpG Adjuvant 1018: A Case Study.
- Source :
-
Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2017; Vol. 1494, pp. 15-27. - Publication Year :
- 2017
-
Abstract
- The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides containing unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-containing oligonucleotide sequence termed 1018 through preclinical and clinical testing as an adjuvant for immunization against hepatitis B virus (HBV). 1018 is a short (22-mer) oligonucleotide sequence containing CpG motifs active in both rodents and primates. Preclinical testing of hepatitis B surface antigen (HBsAg) + 1018 in comparison to HBsAg + alum demonstrated induction of substantially higher antibody titers and a favorable safety profile for 1018. Most importantly, clinical studies with HBsAg vaccination consistently demonstrate more rapid induction of protective antibody titers with 1018 compared to alum in all populations studied, including groups that are harder to immunize such as the elderly and immunocompromised individuals. These studies represent the basis for use of the CpG-motif-containing oligonucleotide 1018 as an improved adjuvant for HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-B <superscript>™</superscript> ) is currently in late-stage clinical testing for prophylactic immunization against HBV.
- Subjects :
- Animals
Humans
Mice
Toll-Like Receptor 9 agonists
Toll-Like Receptor 9 immunology
Adjuvants, Immunologic chemistry
Adjuvants, Immunologic pharmacokinetics
Hepatitis B Surface Antigens chemistry
Hepatitis B Surface Antigens immunology
Hepatitis B Surface Antigens pharmacology
Hepatitis B Vaccines chemistry
Hepatitis B Vaccines immunology
Hepatitis B Vaccines pharmacology
Immunization
Immunogenicity, Vaccine
Oligodeoxyribonucleotides chemistry
Oligodeoxyribonucleotides immunology
Oligodeoxyribonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6029
- Volume :
- 1494
- Database :
- MEDLINE
- Journal :
- Methods in molecular biology (Clifton, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 27718183
- Full Text :
- https://doi.org/10.1007/978-1-4939-6445-1_2