Vaccines

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Open AccessReview

The Dichotomy of Tumor Exosomes (TEX) in Cancer Immunity: Is It All in the ConTEXt?

by Katherine E. Kunigelis and Michael W. Graner

Vaccines 2015, 3(4), 1019-1051; https://doi.org/10.3390/vaccines3041019 - 17 Dec 2015

Cited by 56 | Viewed by 7593

Exosomes are virus-sized nanoparticles (30–130 nm) formed intracellularly as intravesicular bodies/intralumenal vesicles within maturing endosomes (“multivesicular bodies”, MVBs). If MVBs fuse with the cell’s plasma membrane, the interior vesicles may be released extracellularly, and are termed “exosomes”. The protein cargo of exosomes consists [...] Read more.

Exosomes are virus-sized nanoparticles (30–130 nm) formed intracellularly as intravesicular bodies/intralumenal vesicles within maturing endosomes (“multivesicular bodies”, MVBs). If MVBs fuse with the cell’s plasma membrane, the interior vesicles may be released extracellularly, and are termed “exosomes”. The protein cargo of exosomes consists of cytosolic, membrane, and extracellular proteins, along with membrane-derived lipids, and an extraordinary variety of nucleic acids. As such, exosomes reflect the status and identity of the parent cell, and are considered as tiny cellular surrogates. Because of this closely entwined relationship between exosome content and the source/status of the parental cell, conceivably exosomes could be used as vaccines against various pathologies, as they contain antigens associated with a given disease, e.g., cancer. Tumor-derived exosomes (TEX) have been shown to be potent anticancer vaccines in animal models, driving antigen-specific T and B cell responses, but much recent literature concerning TEX strongly places the vesicles as powerfully immunosuppressive. This dichotomy suggests that the context in which the immune system encounters TEX is critical in determining immune stimulation versus immunosuppression. Here, we review literature on both sides of this immune coin, and suggest that it may be time to revisit the concept of TEX as anticancer vaccines in clinical settings. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Open AccessArticle

Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

by Shigetaka Shimodaira, Kenji Sano, Koichi Hirabayashi, Terutsugu Koya, Yumiko Higuchi, Yumiko Mizuno, Naoko Yamaoka, Miki Yuzawa, Takashi Kobayashi, Kenichi Ito and Tomonobu Koizumi

Vaccines 2015, 3(4), 1004-1018; https://doi.org/10.3390/vaccines3041004 - 11 Dec 2015

Cited by 28 | Viewed by 6130

Abstract

Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1) class I/II peptides-pulsed [...] Read more.

Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 10⁷ DCs with 1–2 KE of OK-432 (streptococcal preparation) in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assays. WT1 expression with human leukocyte antigen (HLA)-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer. Full article

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Open AccessReview

Application of Oral Fluid Assays in Support of Mumps, Rubella and Varicella Control Programs

by Peter A. C. Maple

Vaccines 2015, 3(4), 988-1003; https://doi.org/10.3390/vaccines3040988 - 09 Dec 2015

Cited by 6 | Viewed by 5882

Abstract

Detection of specific viral antibody or nucleic acid produced by infection or immunization, using oral fluid samples, offers increased potential for wider population uptake compared to blood sampling. This methodology is well established for the control of HIV and measles infections, but can [...] Read more.

Detection of specific viral antibody or nucleic acid produced by infection or immunization, using oral fluid samples, offers increased potential for wider population uptake compared to blood sampling. This methodology is well established for the control of HIV and measles infections, but can also be applied to the control of other vaccine preventable infections, and this review describes the application of oral fluid assays in support of mumps, rubella and varicella national immunization programs. In England and Wales individuals with suspected mumps or rubella, based on clinical presentation, can have an oral fluid swab sample taken for case confirmation. Universal varicella immunization of children has led to a drastic reduction of chickenpox in those countries where it is used; however, in England and Wales such a policy has not been instigated. Consequently, in England and Wales most children have had chickenpox by age 10 years; however, small, but significant, numbers of adults remain susceptible. Targeted varicella zoster virus (VZV) immunization of susceptible adolescents offers the potential to reduce the pool of susceptible adults and oral fluid determination of VZV immunity in adolescents is a potential means of identifying susceptible individuals in need of VZV vaccination. The main application of oral fluid testing is in those circumstances where blood sampling is deemed not necessary, or is undesirable, and when the documented sensitivity and specificity of the oral fluid assay methodology to be used is considered sufficient for the purpose intended. Full article

(This article belongs to the Special Issue Age-Specific Immune Response to Vaccination)

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Open AccessArticle

Immune Response of Multiparous Hyper-Immunized Sows against Peptides from Non-Structural and Structural Proteins of PRRSV

by Edgar Rascón-Castelo, Alexel Burgara-Estrella, Mónica Reséndiz-Sandoval, Andrés Hernández-Lugo and Jesús Hernández

Vaccines 2015, 3(4), 973-987; https://doi.org/10.3390/vaccines3040973 - 27 Nov 2015

Cited by 4 | Viewed by 5136

Abstract

The purpose of this study was to evaluate the humoral and cellular responses of commercial multiparous and hyper-immunized sows against peptides from non-structural (nsp) and structural proteins of porcine reproductive and respiratory syndrome virus (PRRSV). We selected sows with different numbers of parities [...] Read more.

The purpose of this study was to evaluate the humoral and cellular responses of commercial multiparous and hyper-immunized sows against peptides from non-structural (nsp) and structural proteins of porcine reproductive and respiratory syndrome virus (PRRSV). We selected sows with different numbers of parities from a commercial farm. Management practices on this farm include the use of the MLV commercial vaccine four times per year, plus two vaccinations during the acclimation period. The humoral response was evaluated via the antibody recognition of peptides from nsp and structural proteins, and the cellular response was assessed by measuring the frequency of peptide and PRRSV-specific IFN-gamma-secreting cells (IFNγ-SC). Our results show that sows with six parities have more antibodies against peptides from structural proteins than against peptides from nsp. The analysis of the cellular response revealed that the number of immunizations did not affect the frequency of IFNγ-SC and that the response was stronger against peptides from structural proteins (M protein) than against nsp (nsp2). In summary, these results demonstrate that multiparous, hyper-immunized sows have a stronger immune humoral response to PRRSV structural peptides than nsp, but no differences in IFNγ-SC against the same peptides were observed. Full article

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Open AccessReview

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

by Ivan Y. C. Lin, Thi Thu Hao Van and Peter M. Smooker

Vaccines 2015, 3(4), 940-972; https://doi.org/10.3390/vaccines3040940 - 10 Nov 2015

Cited by 86 | Viewed by 29074

Abstract

Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have [...] Read more.

Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA) are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined. Full article

(This article belongs to the Special Issue Vaccine Delivery)

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Open AccessReview

From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology

by Diana Boraschi and Paola Italiani

Vaccines 2015, 3(4), 930-939; https://doi.org/10.3390/vaccines3040930 - 05 Nov 2015

Cited by 52 | Viewed by 7724

Abstract

In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about [...] Read more.

In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1β. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge), which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Open AccessReview

The Use of Synthetic Carriers in Malaria Vaccine Design

by Liam Powles, Sue D. Xiang, Cordelia Selomulya and Magdalena Plebanski

Vaccines 2015, 3(4), 894-929; https://doi.org/10.3390/vaccines3040894 - 29 Oct 2015

Cited by 22 | Viewed by 10208

Abstract

Malaria vaccine research has been ongoing since the 1980s with limited success. However, recent improvements in our understanding of the immune responses required to combat each stage of infection will allow for intelligent design of both antigens and their associated delivery vaccine vehicles/vectors. [...] Read more.

Malaria vaccine research has been ongoing since the 1980s with limited success. However, recent improvements in our understanding of the immune responses required to combat each stage of infection will allow for intelligent design of both antigens and their associated delivery vaccine vehicles/vectors. Synthetic carriers (also known as vectors) are usually particulate and have multiple properties, which can be varied to control how an associated vaccine interacts with the host, and consequently how the immune response develops. This review comprehensively analyzes both historical and recent studies in which synthetic carriers are used to deliver malaria vaccines. Furthermore, the requirements for a synthetic carrier, such as size, charge, and surface chemistry are reviewed in order to understand the design of effective particle-based vaccines against malaria, as well as providing general insights. Synthetic carriers have the ability to alter and direct the immune response, and a better control of particle properties will facilitate improved vaccine design in the near future. Full article

(This article belongs to the Special Issue Vaccine Delivery)

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Open AccessArticle

A Nanoparticle Based Sp17 Peptide Vaccine Exposes New Immuno-Dominant and Species Cross-reactive B Cell Epitopes

by Sue D. Xiang, Qian Gao, Kirsty L. Wilson, Arne Heyerick and Magdalena Plebanski

Vaccines 2015, 3(4), 875-893; https://doi.org/10.3390/vaccines3040875 - 29 Oct 2015

Cited by 9 | Viewed by 5431

Abstract

Sperm protein antigen 17 (Sp17), expressed in primary as well as in metastatic lesions in >83% of patients with ovarian cancer, is a promising ovarian cancer vaccine candidate. Herein we describe the formulation of nanoparticle based vaccines based on human Sp17 (hSp17) sequence [...] Read more.

Sperm protein antigen 17 (Sp17), expressed in primary as well as in metastatic lesions in >83% of patients with ovarian cancer, is a promising ovarian cancer vaccine candidate. Herein we describe the formulation of nanoparticle based vaccines based on human Sp17 (hSp17) sequence derived peptides, and map the immuno-dominant T cell and antibody epitopes induced using such formulations. The primary T and B cell immuno-dominant region within Sp17 was found to be the same when using biocompatible nanoparticle carriers or the conventional “mix-in” pro-inflammatory adjuvant CpG, both mapping to amino acids (aa) 111–142. However, delivery of hSp17_111–142 as a nanoparticle conjugate promoted a number of new properties, changing the dominant antibody isotype induced from IgG2a to IgG1 and the fine specificity of the B cell epitopes within hSp17_111–142, from an immuno-dominant region 134–142 aa for CpG, to region 121–138 aa for nanoparticles. Associated with this change in specificity was a substantial increase in antibody cross-reactivity between mouse and human Sp17. These results indicate conjugation of antigen to nanoparticles can have major effects on fine antigen specificity, which surprisingly could be beneficially used to increase the cross-reactivity of antibody responses. Full article

(This article belongs to the Special Issue Vaccine Delivery)

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Open AccessArticle

A Synthetic Virus-Like Particle Streptococcal Vaccine Candidate Using B-Cell Epitopes from the Proline-Rich Region of Pneumococcal Surface Protein A

by Marco Tamborrini, Nina Geib, Aniebrys Marrero-Nodarse, Maja Jud, Julia Hauser, Celestine Aho, Araceli Lamelas, Armando Zuniga, Gerd Pluschke, Arin Ghasparian and John A. Robinson

Vaccines 2015, 3(4), 850-874; https://doi.org/10.3390/vaccines3040850 - 16 Oct 2015

Cited by 22 | Viewed by 6490

Abstract

Alternatives to the well-established capsular polysaccharide-based vaccines against Streptococcus pneumoniae that circumvent limitations arising from limited serotype coverage and the emergence of resistance due to capsule switching (serotype replacement) are being widely pursued. Much attention is now focused on the development of recombinant [...] Read more.

Alternatives to the well-established capsular polysaccharide-based vaccines against Streptococcus pneumoniae that circumvent limitations arising from limited serotype coverage and the emergence of resistance due to capsule switching (serotype replacement) are being widely pursued. Much attention is now focused on the development of recombinant subunit vaccines based on highly conserved pneumococcal surface proteins and virulence factors. A further step might involve focusing the host humoral immune response onto protective protein epitopes using as immunogens structurally optimized epitope mimetics. One approach to deliver such epitope mimetics to the immune system is through the use of synthetic virus-like particles (SVLPs). SVLPs are made from synthetic coiled-coil lipopeptides that are designed to spontaneously self-assemble into 20–30 nm diameter nanoparticles in aqueous buffer. Multivalent display of epitope mimetics on the surface of SVLPs generates highly immunogenic nanoparticles that elicit strong epitope-specific humoral immune responses without the need for external adjuvants. Here, we set out to demonstrate that this approach can yield vaccine candidates able to elicit a protective immune response, using epitopes derived from the proline-rich region of pneumococcal surface protein A (PspA). These streptococcal SVLP-based vaccine candidates are shown to elicit strong humoral immune responses in mice. Following active immunization and challenge with lethal doses of streptococcus, SVLP-based immunogens are able to elicit significant protection in mice. Furthermore, a mimetic-specific monoclonal antibody is shown to mediate partial protection upon passive immunization. The results show that SVLPs combined with synthetic epitope mimetics may have potential for the development of an effective vaccine against Streptococcus pneumoniae. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Open AccessArticle

Layer-By-Layer Nanoparticle Vaccines Carrying the G Protein CX3C Motif Protect against RSV Infection and Disease

by Patricia A. Jorquera, Katie E. Oakley, Thomas J. Powell, Naveen Palath, James G. Boyd and Ralph A. Tripp

Vaccines 2015, 3(4), 829-849; https://doi.org/10.3390/vaccines3040829 - 12 Oct 2015

Cited by 21 | Viewed by 5560

Abstract

Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to [...] Read more.

Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to the RSV G glycoprotein CX3C motif, mediates virus clearance and decreases leukocyte trafficking to the lungs of RSV-infected mice. In this study, we show that vaccination with layer-by-layer nanoparticles (LbL-NP) carrying the G protein CX3C motif induces blocking antibodies that prevent the interaction of the RSV G protein with the fractalkine receptor (CX3CR1) and protect mice against RSV replication and disease pathogenesis. Peptides with mutations in the CX3C motif induced antibodies with diminished capacity to block G protein-CX3CR1 binding. Passive transfer of these anti-G protein antibodies to mice infected with RSV improved virus clearance and decreased immune cell trafficking to the lungs. These data suggest that vaccination with LbL-NP loaded with the CX3C motif of the RSV G protein can prevent manifestations of RSV disease by preventing the interaction between the G protein and CX3CR1 and recruitment of immune cells to the airways. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Open AccessReview

Cell Membrane-Coated Nanoparticles As an Emerging Antibacterial Vaccine Platform

by Pavimol Angsantikul, Soracha Thamphiwatana, Weiwei Gao and Liangfang Zhang

Vaccines 2015, 3(4), 814-828; https://doi.org/10.3390/vaccines3040814 - 06 Oct 2015

Cited by 51 | Viewed by 10990

Abstract

Nanoparticles have demonstrated unique advantages in enhancing immunotherapy potency and have drawn increasing interest in developing safe and effective vaccine formulations. Recent technological advancement has led to the discovery and development of cell membrane-coated nanoparticles, which combine the rich functionalities of cellular membranes [...] Read more.

Nanoparticles have demonstrated unique advantages in enhancing immunotherapy potency and have drawn increasing interest in developing safe and effective vaccine formulations. Recent technological advancement has led to the discovery and development of cell membrane-coated nanoparticles, which combine the rich functionalities of cellular membranes and the engineering flexibility of synthetic nanomaterials. This new class of biomimetic nanoparticles has inspired novel vaccine design strategies with strong potential for modulating antibacterial immunity. This article will review recent progress on using cell membrane-coated nanoparticles for antibacterial vaccination. Specifically, two major development strategies will be discussed, namely (i) vaccination against virulence factors through bacterial toxin sequestration; and (ii) vaccination against pathogens through mimicking bacterial antigen presentation. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Open AccessReview

Micelle-Based Adjuvants for Subunit Vaccine Delivery

by Thomas Trimaille and Bernard Verrier

Vaccines 2015, 3(4), 803-813; https://doi.org/10.3390/vaccines3040803 - 25 Sep 2015

Cited by 50 | Viewed by 10300

Abstract

In the development of subunit vaccines with purified or recombinant antigens for cancer and infectious diseases, the design of improved and safe adjuvants able to efficiently target the antigen presenting cells, such as dendritic cells, represents a crucial challenge. Nanoparticle-based antigen delivery systems [...] Read more.

In the development of subunit vaccines with purified or recombinant antigens for cancer and infectious diseases, the design of improved and safe adjuvants able to efficiently target the antigen presenting cells, such as dendritic cells, represents a crucial challenge. Nanoparticle-based antigen delivery systems have been identified as an innovative strategy to improve the efficacy of subunit vaccines. Among them, self-assembled micellar nanoparticles from amphiphilic (macro)molecules have recently emerged as promising candidates. In this short review, we report on the recent research findings highlighting the versatility and potential of such systems in vaccine delivery. Full article

(This article belongs to the Special Issue Nanoparticle-Based Vaccines)

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Vaccines, Volume 3, Issue 4 (December 2015) – 12 articles , Pages 803-1051

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