CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults

Cooper, Curtis; Davis, Heather L.; Angel, Jonathan B.; Morris, Mary L.; Elfer, Sue M; Seguin, Isabelle; Krieg, Arthur Μ.; Cameron, D W

doi:10.1097/01.aids.0000183514.37513.d2

Cited by 179 publications

(138 citation statements)

References 29 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…There are currently phase 2 trials of TLR9 agonists for treatment of chronic hepatitis C, and also as an adjuvant for vaccinations for influenza and anthrax. 33,34 Enhancement for the immune system as a treatment of melanoma and other cancers is also under investigation in human studies. 35 The ability of TLR9 agonists to stimulate a Th1 response and suppress a Th2 response also makes them attractive candidates for therapy in immune diseases that are dependent on a Th2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9

et al. 2007

View full text Add to dashboard Cite

Apoptosis of hepatocytes results in the development of liver fibrosis, but the molecular signals mediating this are poorly understood. Degradation and modification of nuclear DNA is a central feature of apoptosis, and DNA from apoptotic mammalian cells is known to activate immune cells via Toll-like receptor 9 (TLR9). We tested if DNA from apoptotic hepatocytes can induce hepatic stellate cell (HSC) differentiation. Our data show that apoptotic hepatocyte DNA and cytidine-phosphate-guanosine oligonucleotides induced up-regulation of transforming growth factor ␤1 and collagen 1 messenger RNA both in the human HSC line LX-2 and in primary mouse HSCs. These effects were opposed by TLR9 antagonists. We have recently shown that adenosine inhibits HSC chemotaxis, and we now show that apoptotic hepatocyte DNA also inhibits platelet-derived growth factor (PDGF)-mediated HSC chemotaxis.

show abstract

Section: Discussionmentioning

confidence: 99%

Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Furthermore, in a phase I human study in healthy volunteers, addition of CpG to a commercial HBV vaccine that also contains alum induced significantly faster and higher levels of HBV-specific antibodies [37] of significantly enhanced avidity [47]. A subsequent phase II trial in HIV-infected subjects who had failed to respond adequately to previous HBV vaccination produced similar results [36]. All of these features made the CpG/alum adjuvant combination of interest to test with the vaccinia proteins.…”

Section: Discussionmentioning

confidence: 89%

“…In the setting of a smallpox outbreak, this goal would allow safe vaccination of large populations of unexposed but susceptible hosts [32,33]. We selected the adjuvant CpG-ODN, a synthetic toll-like receptor (TLR)-9 agonist [34], which has shown promise as a potent adjuvant to other protein subunit vaccines in various animal models [35,36] as well as in humans [36,37]. We also investigated if this approach would require the addition of a fourth viral protein target.…”

Section: Introductionmentioning

confidence: 99%

A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost

Xiao

Aldaz-Carroll

Ortiz

et al. 2007

Vaccine

104

View full text Add to dashboard Cite

The heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. While subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. Here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. Mice vaccinated with vaccinia virus envelope proteins from the mature virus (MV) and extracellular virus (EV) adjuvanted with CpG-ODN and alum were protected from lethal intranasal challenge with vaccinia virus and the mousespecific ectromelia virus. Organs from mice vaccinated with three proteins (A33, B5 and L1) and then sacrificed after challenge contained significantly lower titers of virus when compared to control groups of mice that were not vaccinated or that received sub-optimal formulations of the vaccine. Sera from groups of mice obtained prior to challenge had neutralizing activity against the MV and also inhibited comet formation indicating anti-EV activity. Long-term partial protection was also seen in mice challenged with vaccinia virus 6 months after initial vaccinations. Thus, this work represents a step toward the development of a practical subunit smallpox vaccine.

show abstract

“…In humans, CPG 7909 has substantially boosted antibody response with Hepatitis B Surface Antigen [17,18] and with AMA1 (Mullen et al, unpublished) and MSP1 42 (Martin et al, unpublished) when these antigens were formulated with alum, but not with the un-adjuvanted influenza vaccine [19]. The mouse data presented in this paper are consistent with these human studies, and both are consistent with studies that show a substantial enhancement of antibody production with CpG covalently linked to the antigen [20].…”

Section: Discussionmentioning

confidence: 99%

“…The addition of CPG 7909 significantly increased antigen-specific antibody titers and enhanced the avidity maturation of IgG1 to hepatitis B surface antigen [9]. In a second Phase 1 trial with Engerix-B ® , CPG 7909 was able to stimulate antibody response in immuno-compromised HIV infected recipients [10]. CPG 7909 is currently being tested in human Phase 1 vaccine trials with several other vaccine candidates, including the malaria antigens Merozoite Surface Protein 1 (MSP1 42) [11] and Apical Membrane Antigen 1 (AMA1) [12], both of which are adsorbed to aluminum hydroxide (Alhydrogel).…”

Section: Introductionmentioning

confidence: 98%

Enhanced antibody production in mice to the malaria antigen AMA1 by CPG 7909 requires physical association of CpG and antigen

Mullen

Aebig

Dobrescu

et al. 2007

Vaccine

View full text Add to dashboard Cite

CpG oligodeoxynucleotides are potent immunostimulants. In this study, CPG 7909 was formulated with the recombinant Plasmodium falciparum protein AMA1-C1 adsorbed to Alhydrogel (aluminum hydroxide) and used to immunize mice. Mice receiving free CPG 7909 in a separate same site injection to the AMA1-C1/Alhydrogel had the same antibody responses as mice receiving AMA1-C1/Alhydrogel alone. For mice immunized with CPG 7909 bound to the AMA1-C1/Alhydrogel formulation, there was a bell shaped CPG 7909 dose response curve with the highest antibody response co-incident with the concentration of CPG 7909 that saturated binding to the Alhydrogel. At a higher CPG 7909 dose where 74% was unbound, there was no enhancement of response over AMA1-C1/Alhydrogel alone. Our results suggest that the adjuvant effects of CpGs are optimal when adsorbed to Alhydrogel and highlight the need for careful characterization of the vaccine formulation.

show abstract

CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults

Cited by 179 publications

References 29 publications

Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9

Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9

A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost

Enhanced antibody production in mice to the malaria antigen AMA1 by CPG 7909 requires physical association of CpG and antigen

Contact Info

Product

Resources

About