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Nanoparticles to Co-Deliver Immunopotentiators and Antigens

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

Deadline for manuscript submissions: closed (15 July 2016) | Viewed by 80941

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Special Issue Editor

Prof. Dr. Olga Borges

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Guest Editor

Center for Neurosciences and Cell Biology (CNC), Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
Interests: preparation methods to obtain antigen and/or immunopotentiator-loaded polymeric nanoparticles; physicochemical characterization of the nanoparticles using standardized methods and protocols; interaction studies of the nanoparticles with biological membranes and with immune cells; immunotoxicological tests with nanoparticles; immunization studies and evaluation of the cellular and humoral immune response
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Special Issue Information

Dear Colleagues,

Antigen delivery systems have primarily been used for protecting and gradually delivering antigens, achieving multimeric antigen presentation or simply mimicking the structure of virus. More recently, it has been reported that, in some cases, a direct effect on innate immune system cells is observed such as inflammasome activation, recognition by toll-like receptors, etc. Therefore, a depth and broad knowledge on the modes of action of the adjuvants will enable to better design nanoparticle-based adjuvants with predictable immune regulation. Since antigens should be close associated with adjuvants, a good strategy would be to construct nanoparticles that would be able to co-delivery immunopotentiators and recombinant antigens. Nanoparticles can have inherent immunopotentiator effect, so, the association or encapsulation of a second immunopotentiator will allow to better modulating the immune response, allowing different applications like the development of immunotherapies, or vaccines for chronic diseases.

This special issue of vaccines will cover topics close related with the emerging approaches in immunobioengineering with specific focus on considerations related with the rationale behind the design of an antigen delivery system, including, besides the recombinant antigen, the encapsulation of substances with immunopotentiator effect or for example the link of molecules that would be recognized by antigen presenting cell surface receptors.

Assist. Prof. Olga Borges
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nanoparticles
co-deliver
immunopotentiators
vaccine adjuvants
modulation of the immune response
Adjuvant mechanistic studies

Published Papers (10 papers)

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Research

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3355 KiB

Open AccessArticle

A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant

by Janina Jiang, Guangchao Liu, Valerie A. Kickhoefer, Leonard H. Rome, Lin-Xi Li, Stephen J. McSorley and Kathleen A. Kelly

Vaccines 2017, 5(1), 3; https://doi.org/10.3390/vaccines5010003 - 19 Jan 2017

Cited by 26 | Viewed by 6622

Abstract

Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a C. muridarum challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a Chlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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2527 KiB

Open AccessArticle

Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice

by Elizabeth A. Thoryk, Gokul Swaminathan, Steven Meschino, Kara S. Cox, Marian Gindy, Danilo R. Casimiro and Andrew J. Bett

Vaccines 2016, 4(4), 47; https://doi.org/10.3390/vaccines4040047 - 06 Dec 2016

Cited by 15 | Viewed by 7754

Abstract

A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs) markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg) and Ovalbumin (OVA), respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h. We also evaluated formulations combining antigen, LNP, and aluminum-based adjuvant amorphous aluminum hydroxylphosphate sulfate (MAA) to look for synergistic adjuvant effects. Analyses of antigen-specific B-cell and T-cell responses from immunized mice revealed that the LNPs and antigens must be co-administered—both at the same time and in the same location—in order to boost antigen-specific immune responses. Mixing of antigen with MAA prior to formulation with LNP did not impact the generation of antigen-specific B-cell responses, but drastically reduced the ability of LNPs to boost antigen-specific T-cell responses. Overall, our data demonstrate that the administration of LNPs and vaccine antigen together enables their immune-stimulatory properties. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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2954 KiB

Open AccessArticle

The CD8⁺ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIX^TM Adjuvant

by Francesco Manfredi, Paola Di Bonito, Barbara Ridolfi, Simona Anticoli, Claudia Arenaccio, Chiara Chiozzini, Adriana Baz Morelli and Maurizio Federico

Vaccines 2016, 4(4), 42; https://doi.org/10.3390/vaccines4040042 - 09 Nov 2016

Cited by 11 | Viewed by 5255

Abstract

We recently described the induction of an efficient CD8⁺ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8⁺ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8⁺ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting. By considering HPV-E6 as a model of TAA, we found that the in vitro co-administration of engineered exosomes and ISCOMATRIX^TM adjuvant, i.e., an adjuvant composed of purified ISCOPREP^TM saponin, cholesterol, and phospholipids, led to a stronger antigen cross-presentation in both B- lymphoblastoid cell lines ( and monocyte-derived immature dendritic cells compared with that induced by the exosomes alone. Consistently, the co-inoculation in mice of ISCOMATRIX^TM adjuvant and engineered exosomes induced a significant increase of TAA-specific CD8⁺ T cells compared to mice immunized with the exosomes alone. This result holds promise for effective usage of exosomes as well as alternative nanovesicles in anti-tumor therapeutic approaches. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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3387 KiB

Open AccessArticle

Edwardsiella tarda OmpA Encapsulated in Chitosan Nanoparticles Shows Superior Protection over Inactivated Whole Cell Vaccine in Orally Vaccinated Fringed-Lipped Peninsula Carp (Labeo fimbriatus)

by Saurabh Dubey, Kiran Avadhani, Srinivas Mutalik, Sangeetha Madambithara Sivadasan, Biswajit Maiti, Shivani Kallappa Girisha, Moleyur Nagarajappa Venugopal, Stephen Mutoloki, Øystein Evensen, Indrani Karunasagar and Hetron Mweemba Munang′andu

Vaccines 2016, 4(4), 40; https://doi.org/10.3390/vaccines4040040 - 07 Nov 2016

Cited by 35 | Viewed by 6903

Abstract

The use of oral vaccination in finfish has lagged behind injectable vaccines for a long time as oral vaccines fall short of injection vaccines in conferring protective immunity. Biodegradable polymeric nanoparticles (NPs) have shown potential to serve as antigen delivery systems for oral vaccines. In this study the recombinant outer membrane protein A (rOmpA) of Edwardsiella tarda was encapsulated in chitosan NPs (NP-rOmpA) and used for oral vaccination of Labeo fimbriatus. The rOmpA purity was 85%, nanodiameter <500 nm, encapsulation efficiency 60.6%, zeta potential +19.05 mV, and there was an in vitro release of 49% of encapsulated antigen within 48 h post incubation in phosphate-buffered saline. Empty NPs and a non-formulated, inactivated whole cell E. tarda (IWC-ET) vaccine were used as controls. Post-vaccination antibody levels were significantly (p = 0.0458) higher in the NP-rOmpA vaccinated fish (Mean OD₄₅₀ = 2.430) than in fish vaccinated with inactivated whole cell E. tarda (IWC-ET) vaccine (Mean OD₄₅₀ = 1.735), which corresponded with post-challenge survival proportions (PCSP) of 73.3% and 48.28% for the NP-rOmpA and IWC-ET groups, respectively. Serum samples from NP-rOmpA-vaccinated fish had a higher inhibition rate for E. tarda growth on tryptic soy agar (TSA) than the IWC-ET group. There was no significant difference (p = 0.989) in PCSPs between fish vaccinated with empty NPs and the unvaccinated control fish, while serum from both groups showed no detectable antibodies against E. tarda. Overall, these data show that the NP-rOmpA vaccine produced higher antibody levels and had superior protection over the IWC-ET vaccine, showing that encapsulating OmpA in chitosan NPs confer improved protection against E. tarda mortality in L. fimbriatus. There is a need to elucidate the possible adjuvant effects of chitosan NPs and the immunological mechanisms of protective immunity induced by OMPs administered orally to fish. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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1713 KiB

Open AccessArticle

Ag85A DNA Vaccine Delivery by Nanoparticles: Influence of the Formulation Characteristics on Immune Responses

by Johanna Poecheim, Christophe Barnier-Quer, Nicolas Collin and Gerrit Borchard

Vaccines 2016, 4(3), 32; https://doi.org/10.3390/vaccines4030032 - 12 Sep 2016

Cited by 17 | Viewed by 5351

Abstract

The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios of pDNA with cationic trimethyl chitosan (TMC) nanoparticles were characterized for their morphology and physicochemical characteristics (size, zeta potential, loading efficiency and pDNA release profile) applied in vitro for cellular uptake studies and in vivo, to determine the dose-dependent effects of pDNA on immune responses. A selected pDNA/TMC nanoparticle formulation was optimized by the incorporation of muramyl dipeptide (MDP) as an immunostimulatory agent. Cellular uptake investigations in vitro showed saturation to a maximum level upon the increase in the pDNA/TMC nanoparticle ratio, correlating with increasing Th1-related antibody responses up to a definite pDNA dose applied. Moreover, TMC nanoparticles induced clear polarization towards a Th1 response, indicated by IgG2c/IgG1 ratios above unity and enhanced numbers of antigen-specific IFN-γ producing T-cells in the spleen. Remarkably, the incorporation of MDP in TMC nanoparticles provoked a significant additional increase in T-cell-mediated responses induced by pDNA. In conclusion, pDNA-loaded TMC nanoparticles are capable of provoking strong Th1-type cellular and humoral immune responses, with the potential to be further optimized by the incorporation of MDP. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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Graphical abstract

746 KiB

Open AccessArticle

Aeromonas hydrophila OmpW PLGA Nanoparticle Oral Vaccine Shows a Dose-Dependent Protective Immunity in Rohu (Labeo rohita)

by Saurabh Dubey, Kiran Avadhani, Srinivas Mutalik, Sangeetha Madambithara Sivadasan, Biswajit Maiti, Joydeb Paul, Shivani Kallappa Girisha, Moleyur Nagarajappa Venugopal, Stephen Mutoloki, Øystein Evensen, Indrani Karunasagar and Hetron Mweemba Munang’andu

Vaccines 2016, 4(2), 21; https://doi.org/10.3390/vaccines4020021 - 01 Jun 2016

Cited by 54 | Viewed by 8250

Abstract

Aeromonas hydrophila is a Gram-negative bacterium that causes high mortality in different fish species and at different growth stages. Although vaccination has significantly contributed to the decline of disease outbreaks in aquaculture, the use of oral vaccines has lagged behind the injectable vaccines due to lack of proven efficacy, that being from primary immunization or by use of boost protocols. In this study, the outer membrane protein W (OmpW) of A. hydrophila was cloned, purified, and encapsulated in poly d,l-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) for oral vaccination of rohu (Labeo rohita Hamilton). The physical properties of PLGA NPs encapsulating the recombinant OmpW (rOmpW) was characterized as having a diameter of 370–375 nm, encapsulation efficiency of 53% and −19.3 mV zeta potential. In vitro release of rOmpW was estimated at 34% within 48 h of incubation in phosphate-buffered saline. To evaluate the efficacy of the NP-rOmpW oral vaccine, two antigen doses were orally administered in rohu with a high antigen (HiAg) dose that had twice the amount of antigens compared to the low antigen (LoAg) dose. Antibody levels obtained after vaccination showed an antigen dose dependency in which fish from the HiAg group had higher antibody levels than those from the LoAg group. The antibody levels corresponded with post challenge survival proportions (PCSPs) and relative percent survival (RPS) in which the HiAg group had a higher PCSP and RPS than the LoAg group. Likewise, the ability to inhibit A. hydrophila growth on trypticase soy agar (TSA) by sera obtained from the HiAg group was higher than that from the LoAg group. Overall, data presented here shows that OmpW orally administered using PLGA NPs is protective against A. hydrophila infection with the level of protective immunity induced by oral vaccination being antigen dose-dependent. Future studies should seek to optimize the antigen dose and duration of oral immunization in rohu in order to induce the highest protection in vaccinated fish. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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Review

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1231 KiB

Open AccessReview

Harnessing Nanoparticles for Immunomodulation and Vaccines

by Ariane C. Gomes, Mona Mohsen and Martin F. Bachmann

Vaccines 2017, 5(1), 6; https://doi.org/10.3390/vaccines5010006 - 14 Feb 2017

Cited by 115 | Viewed by 9593

Abstract

The first successful use of nanoparticles (NPs) for vaccination was reported almost 40 years ago with a virus-like particle-based vaccine against Hepatitis B. Since then, the term NP has been expanded to accommodate a large number of novel nano-sized particles engineered from a range of materials. The great interest in NPs is likely not only a result of the two successful vaccines against hepatitis B and Human Papilloma Virus (HPV) that use this technology, but also due to the versatility of those small-sized particles, as indicated by the wide range of applications reported so far, ranging from medicinal and cosmetics to purely technical applications. In this review, we will focus on the use of NPs, especially virus-like particles (VLPs), in the field of vaccines and will discuss their employment as vaccines, antigen display platforms, adjuvants and drug delivery systems. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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1315 KiB

Open AccessReview

Synthetic Biodegradable Microparticle and Nanoparticle Vaccines against the Respiratory Syncytial Virus

by Patricia A. Jorquera and Ralph A. Tripp

Vaccines 2016, 4(4), 45; https://doi.org/10.3390/vaccines4040045 - 02 Dec 2016

Cited by 27 | Viewed by 8158

Abstract

Synthetic biodegradable microparticle and nanoparticle platform technology provides the opportunity to design particles varying in composition, size, shape and surface properties for application in vaccine development. The use of particle vaccine formulations allows improvement of antigen stability and immunogenicity while allowing targeted delivery and slow release. This technology has been design to develop novel vaccines against the respiratory syncytial virus (RSV), the leading cause of lower respiratory tract infection in infants. In the last decade, several nano- and micro-sized RSV vaccine candidates have been developed and tested in animal models showing promising results. This review provides an overview of recent advances in prophylactic particle vaccines for RSV and the multiple factors that can affect vaccine efficacy. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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2203 KiB

Open AccessReview

Replicon RNA Viral Vectors as Vaccines

by Kenneth Lundstrom

Vaccines 2016, 4(4), 39; https://doi.org/10.3390/vaccines4040039 - 07 Nov 2016

Cited by 58 | Viewed by 12159

Abstract

Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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2163 KiB

Open AccessReview

Biodegradable Polymeric Nanoparticles-Based Vaccine Adjuvants for Lymph Nodes Targeting

by Alice Gutjahr, Capucine Phelip, Anne-Line Coolen, Claire Monge, Anne-Sophie Boisgard, Stéphane Paul and Bernard Verrier

Vaccines 2016, 4(4), 34; https://doi.org/10.3390/vaccines4040034 - 12 Oct 2016

Cited by 102 | Viewed by 10150

Abstract

Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations. In this review, we describe the properties of different polymer-based (e.g., poly lactic-co-glycolic acid, poly lactic acid …) particulate adjuvants as innovative systems, capable of co-delivering immunopotentiators and antigens. We point out how these nanoparticles enhance the delivery of antigens, and how their physicochemical properties modify their uptake by antigen-presenting cells and their migration into lymph nodes. We describe why polymeric nanoparticles increase the persistence into lymph nodes and promote a mature immune response. We also emphasize how nanodelivery directs the response to a specific antigen and allows the induction of a cytotoxic immune response, essential for the fight against intracellular pathogens or cancer. Finally, we highlight the interest of the association between polymer-based vaccines and immunopotentiators, which can potentiate the effect of the molecule by directing it to the appropriate compartment and reducing its toxicity. Full article

(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)

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