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Peptide Vaccines for Hypertension and Diabetes Mellitus.

Nakagami H, Koriyama H, Morishita R - Vaccines (Basel) (2014)

Bottom Line: However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines.Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4.In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus.

View Article: PubMed Central - PubMed

Affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University, Fukui University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan. nakagami@cgt.med.osaka-u.ac.jp.

ABSTRACT
Vaccines are commonly used as a preventive medicine for infectious diseases worldwide; however, the trial for an amyloid beta vaccine against Alzheimer's disease will open a new concept in vaccination. In case of therapeutic vaccines for cancer, their targets are usually specific antigens in cancer cells, allowing activated cytotoxic T cells (CTLs) to attach and remove the antigen-presenting cancer cells. In our therapeutic vaccines against hypertension, the target is angiotensin II (Ang II) and induced anti-Ang II antibodies could efficiently ameliorate high blood pressure. Similarly, we developed the therapeutic vaccine against DPP4 for diabetes mellitus. However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines. Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4. In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus.

No MeSH data available.


Related in: MedlinePlus

Conceptual schematic of therapeutic vaccine. (Step1) The antigen-presenting cells (APCs) (the antigen, i.e., Ang II or DPP4, in this case is known as a hapten) phagocytose the antigen-KLH conjugate and present a T-cell epitope of KLH to T-cells through the major histocompatibility complex (MHC). T-cells recognize it through T-cell receptors and become activated. (Step2) B-cells specifically recognizing the target antigen differentiate into plasmacytes and proliferate with the help of activated T-cells. Then, B-cells produce anti-angiotensin II (Ang II) or DPP4 antibody.
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vaccines-02-00832-f001: Conceptual schematic of therapeutic vaccine. (Step1) The antigen-presenting cells (APCs) (the antigen, i.e., Ang II or DPP4, in this case is known as a hapten) phagocytose the antigen-KLH conjugate and present a T-cell epitope of KLH to T-cells through the major histocompatibility complex (MHC). T-cells recognize it through T-cell receptors and become activated. (Step2) B-cells specifically recognizing the target antigen differentiate into plasmacytes and proliferate with the help of activated T-cells. Then, B-cells produce anti-angiotensin II (Ang II) or DPP4 antibody.

Mentions: We show the concept of our therapeutic vaccine in Figure 1. Stable and sufficient antibody production requires helper T-cell activation to assist in the polyclonal expansion of B-cells; therefore, antigens must contain both B-cell and T-cell epitopes. As we want to avoid T-cell epitopes from our target molecule, immunogenic molecules (i.e., KLH) are conjugated with the antigen. Consequently, T-cells would be activated by KLH, instead of the epitopes of our target molecule. We need to confirm that antibodies against our target molecule (i.e., Angiotensin II) are successfully induced after immunization with our target molecule, thereby confirming the existence of a B-cell epitope on our target molecule. As for T-cell epitopes, we will perform T-cell proliferation assays and ELISPOT assays, which may indicate to us the responsiveness of T-cells to our target molecule. Ang II-KLH has been used as an Ang II peptide vaccine in mice. The results indicated that Ang II-KLH and KLH induced T-cell activation but Ang II did not, which means that KLH contains a T-cell epitope, but Ang II does not [23]. Importantly, the sources of T-cell epitopes and B-cell epitopes can be different. This situation is reflected in the relationship between a hapten and its carrier, in which the hapten has the only B-cell epitope and the carrier possesses the T-cell epitope. Based on this mechanism for our therapeutic vaccine system, autoimmune diseases caused by cytotoxic T-cells can be avoided.


Peptide Vaccines for Hypertension and Diabetes Mellitus.

Nakagami H, Koriyama H, Morishita R - Vaccines (Basel) (2014)

Conceptual schematic of therapeutic vaccine. (Step1) The antigen-presenting cells (APCs) (the antigen, i.e., Ang II or DPP4, in this case is known as a hapten) phagocytose the antigen-KLH conjugate and present a T-cell epitope of KLH to T-cells through the major histocompatibility complex (MHC). T-cells recognize it through T-cell receptors and become activated. (Step2) B-cells specifically recognizing the target antigen differentiate into plasmacytes and proliferate with the help of activated T-cells. Then, B-cells produce anti-angiotensin II (Ang II) or DPP4 antibody.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494253&req=5

vaccines-02-00832-f001: Conceptual schematic of therapeutic vaccine. (Step1) The antigen-presenting cells (APCs) (the antigen, i.e., Ang II or DPP4, in this case is known as a hapten) phagocytose the antigen-KLH conjugate and present a T-cell epitope of KLH to T-cells through the major histocompatibility complex (MHC). T-cells recognize it through T-cell receptors and become activated. (Step2) B-cells specifically recognizing the target antigen differentiate into plasmacytes and proliferate with the help of activated T-cells. Then, B-cells produce anti-angiotensin II (Ang II) or DPP4 antibody.
Mentions: We show the concept of our therapeutic vaccine in Figure 1. Stable and sufficient antibody production requires helper T-cell activation to assist in the polyclonal expansion of B-cells; therefore, antigens must contain both B-cell and T-cell epitopes. As we want to avoid T-cell epitopes from our target molecule, immunogenic molecules (i.e., KLH) are conjugated with the antigen. Consequently, T-cells would be activated by KLH, instead of the epitopes of our target molecule. We need to confirm that antibodies against our target molecule (i.e., Angiotensin II) are successfully induced after immunization with our target molecule, thereby confirming the existence of a B-cell epitope on our target molecule. As for T-cell epitopes, we will perform T-cell proliferation assays and ELISPOT assays, which may indicate to us the responsiveness of T-cells to our target molecule. Ang II-KLH has been used as an Ang II peptide vaccine in mice. The results indicated that Ang II-KLH and KLH induced T-cell activation but Ang II did not, which means that KLH contains a T-cell epitope, but Ang II does not [23]. Importantly, the sources of T-cell epitopes and B-cell epitopes can be different. This situation is reflected in the relationship between a hapten and its carrier, in which the hapten has the only B-cell epitope and the carrier possesses the T-cell epitope. Based on this mechanism for our therapeutic vaccine system, autoimmune diseases caused by cytotoxic T-cells can be avoided.

Bottom Line: However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines.Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4.In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus.

View Article: PubMed Central - PubMed

Affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University, Fukui University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan. nakagami@cgt.med.osaka-u.ac.jp.

ABSTRACT
Vaccines are commonly used as a preventive medicine for infectious diseases worldwide; however, the trial for an amyloid beta vaccine against Alzheimer's disease will open a new concept in vaccination. In case of therapeutic vaccines for cancer, their targets are usually specific antigens in cancer cells, allowing activated cytotoxic T cells (CTLs) to attach and remove the antigen-presenting cancer cells. In our therapeutic vaccines against hypertension, the target is angiotensin II (Ang II) and induced anti-Ang II antibodies could efficiently ameliorate high blood pressure. Similarly, we developed the therapeutic vaccine against DPP4 for diabetes mellitus. However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines. Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4. In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus.

No MeSH data available.


Related in: MedlinePlus