Co-administration of a CpG adjuvant (VaxImmuneTM, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice

Thomas, Lawrence J.; Hammond, Russell A.; Forsberg, Eric M.; Geoghegan-Barek, Kathleen; Karalius, Brad; Marsh, Henry C.; Rittershaus, Charles W.

doi:10.4161/hv.5.2.6521

Cited by 28 publications

(12 citation statements)

References 19 publications

(27 reference statements)

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“…The use of vaccines targeting self-antigens has recently been reported for cancer [2], rheumatoid arthritis [1], Alzheimer’s disease [3]–[12], [25], [26], hypertension [6], [13], [14], and dyslipidemia [35]. Because safe and effective drug therapies have already been established for several of these conditions, adverse vaccine effects should be carefully considered, especially in hypertension and dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

et al. 2013

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Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer’s disease in addition to infectious diseases. However, before use in the clinical setting, vaccines targeting self-antigens must be demonstrated to be effective and safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation in response to self. Although the vaccine targeting angiotensin II (Ang II) is efficient in rodents and humans, little is known regarding the immunological activation and safety of the vaccine. In this study, we evaluated the efficiency and safety of an Ang II peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet hemocyanin (KLH) successfully induced the production of anti-Ang II antibody, which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang II itself did not activate T cells, as assessed by the proliferation and lymphokine production of T cells in immunized mice, whereas KLH activated T cells. In an Ang II-infused model, the non-immunized mice showed high blood pressure (BP), whereas the immunized mice (Ang II-KLH) showed a significant decrease in systolic BP, accompanied by significant reductions in cardiac hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not elevated even after the administration of large amounts of Ang II, indicating that Ang II itself boosted antibody production, most likely due to less activation of T cells. In addition, no accumulation of inflammatory cells was observed in immunized mice, because endogenous Ang II would not activate T cells after immunization with Ang II-KLH. Taken together, these data indicate that vaccines targeting Ang II might be effective to decrease high BP and prevent cardiovascular complications without severe side effects.

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Section: Discussionmentioning

confidence: 99%

Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

et al. 2013

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“…In this study, titers of anti-apo(a) antibody were only observed in the apo(a) group, and this immunization led to a Th1-biased immune response. Vaccination against self-antigens has been recently reported in the treatment of cancer32, rheumatoid arthritis33, Alzheimer's disease934353637383940414243, hypertension114445, and dyslipidemia46. The adverse effects of vaccination should be carefully considered, especially in hypertension and dyslipidemia, because safe and effective drug therapies have been already established.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Neointima Formation through DNA Vaccination for Apolipoprotein(a): A New Therapeutic Strategy for Lipoprotein(a)

Kyutoku

Nakagami

Kuroda

et al. 2013

Sci Rep

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Lipoprotein(a) [Lp(a)] is an unique lipoprotein consisting of the glycoprotein apolipoprotein(a) [apo(a)] in low-density lipoprotein. Although Lp(a) is a well-known independent risk factor for cardiovascular disease; however, there is no drugs to decrease plasma Lp(a) level. Thus, to inhibit the biological activity of Lp(a), we developed DNA vaccine for apo(a) by the targeting to the selected 12 hydrophilic amino acids in the kringle-4 type 2 domain of apo(a). Hepatitis B virus core protein was used as an epitope carrier to enhance the immunogenicity. Intramuscular immunization with apo(a) vaccine resulted in the significant inhibition of neointima formation in carotid artery ligation model using Lp(a) transgenic mice, associated with anti-apo(a) antibody and decrease in vascular Lp(a) deposition. Overall, this study provided the first evidence that the pro-atherosclerotic actions of Lp(a) could be prevented by DNA vaccine directed against apo(a), suggesting a novel therapeutic strategy to treat cardiovascular diseases related to high Lp(a).

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“…CETP vaccines are still under development, although early reports suggested that antibody titers were too low to achieve sufficient CETP inhibition [105]. More recently, the immunogenicity of CETP vaccines could be increased by co-administration of a CpG adjuvant in preclinical models [106]. Administration of antisense deoxynucleotides was studied in small animal models and led to increased HDL levels and reduced atherosclerosis compared to experimental controls [30].…”

Section: Cetp Inhibitorsmentioning

confidence: 99%

“…Dalcetrapib increased HDL and demonstrated a favorable safety profile in a phase II study, and no changes in vital signs including blood pressure have been observed [106,107]. A phase III trial to evaluate the effects of 600 mg dalcetrapib compared with a placebo on mortality and morbidity in approximately 15,600 high-risk patients considered to have stable CHD after recent cardiovascular events is currently in progress (The dal-HEART Program: Dalcetrapip HDL Evaluation, Atherosclerosis and Reverse Cholesterol Transport; ClinicalTrials.gov identifier NCT00658515).…”

Section: Cetp Inhibitorsmentioning

confidence: 99%

Cholesteryl ester transfer protein and its inhibition

Weber

Bischoff

Schmeck

et al. 2010

Cell. Mol. Life Sci.

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Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from the atheroprotective high density lipoprotein (HDL) to the proatherogenic low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) leading to lower levels of HDL but raising the levels of proatherogenic LDL and VLDL. Inhibition of CETP is considered a potential approach to treat dyslipidemia. However, discussions regarding the role of CETP-mediated lipid transfer in the development of atherosclerosis and CETP inhibition as a potential strategy for prevention of atherosclerosis have been controversial. Although many animal studies support the hypothesis that inhibition of CETP activity may be beneficial, negative phase III studies on clinical endpoints with the CETP inhibitor torcetrapib challenged the future perspectives of CETP inhibitors as potential therapeutic agents. The review provides an update on current understanding of the molecular mechanisms involved in CETP activity and its inhibition.

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Co-administration of a CpG adjuvant (VaxImmuneTM, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice

Cited by 28 publications

References 19 publications

Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

Inhibition of Neointima Formation through DNA Vaccination for Apolipoprotein(a): A New Therapeutic Strategy for Lipoprotein(a)

Cholesteryl ester transfer protein and its inhibition

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