Nanoparticle-Based Vaccines

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (30 June 2015) | Viewed by 92994

Special Issue Editor

Department of Materials Science & Engineering and Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
Interests: nanoparticle vaccines, HIV vaccines, cancer vaccines, cancer immunotherapy

Special Issue Information

Dear Colleagues,

Among the many strategies pursued to enhance the efficacy of subunit vaccines in recent years, the use of synthetic or biologically-derived nanoparticles as a platform for vaccine delivery is an approach which has both demonstrated clinical success and has much potential for further development. Effective virus-like particle and virosome-based vaccines have become successful clinical products, demonstrating proof of concept for these strategies. In preclinical studies, nanoparticle display of antigens has been shown to enhance antigen delivery to lymphoid tissues, promote effective priming of humoral immunity, and to promote cellular immune responses in both small and large animal models. Further, the capacity of nanoparticles to co-deliver molecular adjuvants that optimize the immune response, to regulate the kinetics of antigen exposure, and to direct vaccine uptake to appropriate antigen presenting cells are all important ongoing areas of research. Understanding the multifaceted mechanisms of action of nanoparticle vaccines remains an important ongoing challenge that will enable these technologies to further impact prophylactic and therapeutic vaccine development. This special issue of Vaccines will cover all of these topics relevant to nanoparticle vaccine design.

Prof. Dr. Darrell J. Irvine
Guest Editor

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Keywords

  • synthetic nanoparticles
  • vaccine delivery
  • virus-like particles
  • vaccine adjuvants

Published Papers (10 papers)

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Research

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893 KiB  
Article
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 6427
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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Article
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 5505
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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Article
Chitosan-Poly (I:C)-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines
by Jorge F. Correia-Pinto, Noemi Csaba, John T. Schiller and Maria J. Alonso
Vaccines 2015, 3(3), 730-750; https://doi.org/10.3390/vaccines3030730 - 11 Sep 2015
Cited by 22 | Viewed by 8183
Abstract
The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells [...] Read more.
The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm), a high positive surface charge (>40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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Review
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 55 | Viewed by 7441
Abstract
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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Review
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 7554
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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336 KiB  
Review
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 50 | Viewed by 10893
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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259 KiB  
Review
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 10231
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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432 KiB  
Review
Gas Vesicle Nanoparticles for Antigen Display
by Shiladitya DasSarma and Priya DasSarma
Vaccines 2015, 3(3), 686-702; https://doi.org/10.3390/vaccines3030686 - 07 Sep 2015
Cited by 38 | Viewed by 7617
Abstract
Microorganisms like the halophilic archaeon Halobacterium sp. NRC-1 produce gas-filled buoyant organelles, which are easily purified as protein nanoparticles (called gas vesicles or GVNPs). GVNPs are non-toxic, exceptionally stable, bioengineerable, and self-adjuvanting. A large gene cluster encoding more than a dozen proteins has [...] Read more.
Microorganisms like the halophilic archaeon Halobacterium sp. NRC-1 produce gas-filled buoyant organelles, which are easily purified as protein nanoparticles (called gas vesicles or GVNPs). GVNPs are non-toxic, exceptionally stable, bioengineerable, and self-adjuvanting. A large gene cluster encoding more than a dozen proteins has been implicated in their biogenesis. One protein, GvpC, found on the exterior surface of the nanoparticles, can accommodate insertions near the C-terminal region and results in GVNPs displaying the inserted sequences on the surface of the nanoparticles. Here, we review the current state of knowledge on GVNP structure and biogenesis as well as available studies on immunogenicity of pathogenic viral, bacterial, and eukaryotic proteins and peptides displayed on the nanoparticles. Recent improvements in genetic tools for bioengineering of GVNPs are discussed, along with future opportunities and challenges for development of vaccines and other applications. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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427 KiB  
Review
Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy
by Yuchen Fan and James J. Moon
Vaccines 2015, 3(3), 662-685; https://doi.org/10.3390/vaccines3030662 - 27 Aug 2015
Cited by 205 | Viewed by 20002
Abstract
Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes [...] Read more.
Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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Review
Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants
by Marie-Ève Lebel, Karine Chartrand, Denis Leclerc and Alain Lamarre
Vaccines 2015, 3(3), 620-637; https://doi.org/10.3390/vaccines3030620 - 05 Aug 2015
Cited by 55 | Viewed by 8046
Abstract
Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; [...] Read more.
Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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