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Open AccessArticle

Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation

by Monique Richter, Agneta Mewes, Manuela Fritsch, Ute Krügel, Ralf Hoffmann and David Singer

Vaccines 2014, 2(3), 601-623; https://doi.org/10.3390/vaccines2030601 - 29 Jul 2014

Cited by 11 | Viewed by 9066

Abstract

Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235) and an [...] Read more.

Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235) and an immunomodulatory T cell epitope from the tetanus toxin or tuberculosis antigen Ag85B. Importantly, the designed vaccine combining Alzheimer’s disease (AD) specific B cell epitopes with foreign (bacterial) T cell epitopes induced fast immune responses with high IgG₁ titers after prophylactic immunization that subsequently decreased over the observation period. The effectiveness of the immunization was surveyed by evaluating the animal behavior, as well as the pathology in the brain by biochemical and histochemical techniques. Immunized mice clearly lived longer with reduced paralysis than placebo-treated mice. Additionally, they performed significantly better in rotarod and beam walk tests at the age of 20 weeks, indicating that the disease development was slowed down. Forty-eight weeks old vaccinated mice passed the beam walk test significantly better than control animals, which together with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Open AccessArticle

Pleurocidin Peptide Enhances Grouper Anti-Vibrio harveyi Immunity Elicited by Poly(lactide-co-glycolide)-Encapsulated Recombinant Glyceraldehyde-3-phosphate Dehydrogenase

by Shu-Chun Chuang, Wan-Ling Huang, Sau-Wei Kau, Yun-Pei Yang and Chung-Da Yang

Vaccines 2014, 2(2), 380-396; https://doi.org/10.3390/vaccines2020380 - 14 May 2014

Cited by 11 | Viewed by 6900

Abstract

Outer membrane proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are considered immunodominant antigens for eliciting protective immunity against Vibrio harveyi, the main etiological agent of vibriosis in fish. Cationic antimicrobial peptides (AMPs), such as pleurocidin (PLE), play important roles in activating and recruiting [...] Read more.

Outer membrane proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are considered immunodominant antigens for eliciting protective immunity against Vibrio harveyi, the main etiological agent of vibriosis in fish. Cationic antimicrobial peptides (AMPs), such as pleurocidin (PLE), play important roles in activating and recruiting immune cells, thereby contributing to subsequent innate and adaptive immune responses. In the present study, we aimed to use PLE peptide as a potent adjuvant to improve the immunogenicity of V. harveyi recombinant GAPDH (rGAPDH). In order to prepare a controlled-release vaccine, PLE peptide and rGAPDH protein were simultaneously encapsulated into polymeric microparticles made from the biodegradable poly(lactide-co-glycolide) (PLG) polymer. The resulting PLG-encapsulated PLE plus rGAPDH (PLG-PLE/rGAPDH) microparticles, 3.21–6.27 μm in diameter, showed 72%–83% entrapment efficiency and durably released both PLE and rGAPDH for a long 30-day period. Following peritoneal immunization in grouper (Epinephelus coioides), PLG-PLE/rGAPDH microparticles resulted in significantly higher (p < 0.05, nested design) long-lasting GAPDH-specific immunity (serum titers and lymphocyte proliferation) than PLG-encapsulated rGAPDH (PLG-rGAPDH) microparticles. After an experimental challenge of V. harveyi, PLG-PLE/rGAPDH microparticles conferred a high survival rate (85%), which was significantly higher (p < 0.05, chi-square test) than that induced by PLG-rGAPDH microparticles (67%). In conclusion, PLE peptide exhibits an efficacious adjuvant effect to elicit not only improved immunity, but also enhanced protection against V. harveyi in grouper induced by rGAPDH protein encapsulated in PLG microparticles. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Review

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Open AccessReview

Peptide Vaccines for Hypertension and Diabetes Mellitus

by Hironori Nakagami, Hiroshi Koriyama and Ryuichi Morishita

Vaccines 2014, 2(4), 832-840; https://doi.org/10.3390/vaccines2040832 - 26 Nov 2014

Cited by 6 | Viewed by 8912

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Open AccessReview

Schistosome Vaccine Adjuvants in Preclinical and Clinical Research

by Rachel Stephenson, Hong You, Donald P. McManus and Istvan Toth

Vaccines 2014, 2(3), 654-685; https://doi.org/10.3390/vaccines2030654 - 02 Sep 2014

Cited by 24 | Viewed by 7862

Abstract

There is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. The bar to achieve protective efficacy in [...] Read more.

There is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. The bar to achieve protective efficacy in humans was set at a consistent induction of 40% protection or better by the World Health Organisation (WHO), and although this is a modest goal, it is yet to be reached with the six most promising schistosomiasis vaccine candidates (Sm28GST, IrV5, Sm14, paramyosin, TPI, and Sm23). Adjuvant selection has a large impact on the effectiveness of the vaccine, and the use of adjuvants to aid in the stimulation of the immune system is a critical step and a major variable affecting vaccine development. In addition to a comprehensive understanding of the immune system, level of protection and the desired immune response required, there is also a need for a standardised and effective adjuvant formulation. This review summarises the status of adjuvants that have been or are being employed in schistosomiasis vaccine development focusing on immunisation outcomes at preclinical and clinical stages. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Strategy for Designing a Synthetic Tumor Vaccine: Multi-Component, Multivalency and Antigen Modification

by Zhi-Hua Huang, Zhan-Yi Sun, Yue Gao, Pu-Guang Chen, Yan-Fang Liu, Yong-Xiang Chen and Yan-Mei Li

Vaccines 2014, 2(3), 549-562; https://doi.org/10.3390/vaccines2030549 - 15 Jul 2014

Cited by 9 | Viewed by 6915

Abstract

Synthetic tumor vaccines have been proven to be promising for cancer immunotherapy. However, the limitation of the specificity and efficiency of the synthetic tumor vaccines need further improvements. To overcome these difficulties, additional tumor-associated targets need to be identified, and optimized structural designs [...] Read more.

Synthetic tumor vaccines have been proven to be promising for cancer immunotherapy. However, the limitation of the specificity and efficiency of the synthetic tumor vaccines need further improvements. To overcome these difficulties, additional tumor-associated targets need to be identified, and optimized structural designs of vaccines need to be elaborated. In this review, we summarized the main strategies pursued in the design of synthetic tumor vaccines, such as multi-component, multivalency, antigen modification and other possible ways to improve the efficiency of synthetic tumor vaccines. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Open AccessReview

Peptide Dose and/or Structure in Vaccines as a Determinant of T Cell Responses

by Graham R. Leggatt

Vaccines 2014, 2(3), 537-548; https://doi.org/10.3390/vaccines2030537 - 02 Jul 2014

Cited by 10 | Viewed by 6853

Abstract

While T cells recognise the complex of peptide and major histocompatibility complex (MHC) at the cell surface, changes in the dose and/or structure of the peptide component can have profound effects on T cell activation and function. In addition, the repertoire of T [...] Read more.

While T cells recognise the complex of peptide and major histocompatibility complex (MHC) at the cell surface, changes in the dose and/or structure of the peptide component can have profound effects on T cell activation and function. In addition, the repertoire of T cells capable of responding to any given peptide is variable, but broader than a single clone. Consequently, peptide parameters that affect the interaction between T cells and peptide/MHC have been shown to select particular T cell clones for expansion and this impacts on clearance of disease. T cells with high functional avidity are selected on low doses of peptide, while low avidity T cells are favoured in high peptide concentrations. Altering the structure of the peptide ligand can also influence the selection and function of peptide-specific T cell clones. In this review, we will explore the evidence that the choice of peptide dose or the structure of the peptide are critical parameters in an effective vaccine designed to activate T cells. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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692 KiB

Open AccessReview

Peptide Vaccine: Progress and Challenges

by Weidang Li, Medha D. Joshi, Smita Singhania, Kyle H. Ramsey and Ashlesh K. Murthy

Vaccines 2014, 2(3), 515-536; https://doi.org/10.3390/vaccines2030515 - 02 Jul 2014

Cited by 475 | Viewed by 25066

Abstract

Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load [...] Read more.

Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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Open AccessReview

Therapeutic Vaccine Strategies against Human Papillomavirus

by Hadeel Khallouf, Agnieszka K. Grabowska and Angelika B. Riemer

Vaccines 2014, 2(2), 422-462; https://doi.org/10.3390/vaccines2020422 - 13 Jun 2014

Cited by 54 | Viewed by 10716

Abstract

High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose [...] Read more.

High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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