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Increased potency of BioThrax anthrax vaccine with the addition of the C-class CpG oligonucleotide adjuvant CPG 10109.

Abstract
The inclusion of an adjuvant, in addition to the existing aluminum hydroxide, in the formulation of the licensed anthrax vaccine BioThrax may have the potential to positively modify immune responses. Some potential desirable outcomes from the inclusion of an additional adjuvant include increased immune response kinetics, increased response rates, more prolonged antibody decay rates, and the ability to use less antigen per dose or fewer doses to achieve immunity. One promising group of adjuvants that is being investigated with a variety of vaccines and which has been shown to cause many of these effects are oligonucleotides which contain unmethylated CpG motifs. The C-class oligonucleotide CPG 10109, constructed of a mixed phosphorothioate/phosphodiester backbone and containing 3 CpG motifs, was added to various dilutions of BioThrax and used in mouse and guinea pig immunogenicity studies. Anti-protective antigen (PA) IgG ELISAs and the anthrax toxin neutralization assay (TNA) were performed on serum samples from both species. Anti-PA IgG and TNA responses were approximately 10-fold higher after a single dose of undiluted or diluted BioThrax upon addition of 100 microg CPG 10109 in the mouse regardless of the route of immunization. Responses were also significantly greater in the guinea pig after receiving CpG-adjuvanted undiluted BioThrax or CpG-adjuvanted BioThrax diluted 1:5, 1:10 or 1:30 compared to those achieved with BioThrax alone. A guinea pig spore challenge study showed that a single injection of BioThrax vaccine diluted 1:10 in the presence of 25 microg CPG 10109 was as protective as undiluted BioThrax, whereas a single injection of BioThrax diluted 1:10 was not protective. Taken together with the results from the immunogenicity studies, these results suggest that a CpG adjuvant could be used to reduce the dose of active ingredient required to elicit a protective response, and could lead to improved immune response kinetics.
AuthorsMili Gu, Paul M Hine, W James Jackson, Lallan Giri, Gary S Nabors
JournalVaccine (Vaccine) Vol. 25 Issue 3 Pg. 526-34 (Jan 05 2007) ISSN: 0264-410X [Print] Netherlands
PMID16973247 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Adjuvants, Immunologic
  • Anthrax Vaccines
  • CPG 10109
  • Immunoglobulin G
  • Immunoglobulin M
  • Oligodeoxyribonucleotides
Topics
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Anthrax (microbiology, prevention & control)
  • Anthrax Vaccines (immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoglobulin G (analysis, biosynthesis)
  • Immunoglobulin M (analysis, biosynthesis)
  • Mice
  • Mice, Inbred DBA
  • Neutralization Tests
  • Oligodeoxyribonucleotides (pharmacology)
  • Survival

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