Nanoparticles to Improve the Efficacy of Vaccines

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 53653

Special Issue Editors


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Guest Editor
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul 08826, Korea
Interests: nanoparticle; nanotechnology; adjuvant; nanovaccinology; polymeric vaccine
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea
Interests: vaccine; adjuvant; immunological memory; innate and adaptive immunity; dendritic cells; cross-presentation; immunometabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Vaccination is a process of introducing (foreign) antigenic material(s) to activate a host immune system to develop inflammatory responses followed by adaptive immunity against a pathogen or cancer. It has been a key strategy to control diseases and has contributed a great deal to improving the quality of life of humans and animals. Despite the presence of successful vaccines, many diseases including severe acute respiratory syndrome (SARS), Ebola virus disease, Zika virus disease, middle eastern respiratory syndrome coronavirus (MERS-CoV) disease, dengue fever, Marburg disease, malaria, and tuberculosis are in need of effective vaccines together with qualified adjuvants. While traditional adjuvants such as alum have been exclusively employed clinically to promote humoral responses, recent development in adjuvant research identified by various potential pathogen-associated molecular patterns (i.e. CpG-ODN, Poly(I:C), and cyclic dinucleotides), a few chemical compounds (i.e. imiquimod and resiquimod), as well as other molecular agonists of toll-like receptors are known to induce strong immune responses.

In the last decade, advancements in material science have opened up a new era of innovative strategies for vaccine design. Moreover, materials science has been widely adopted for vaccine development for strong humoral and cellular immune responses. To evoke appropriate immune responses in humans and animals after vaccination, it is necessary to induce not only innate but also adaptive immunity. As vaccine development pushes toward less immunogenic components such as peptide-based or sub-unit vaccines because of side effects and a life-threatening risk of live attenuated vaccine, strategies to boost both innate and adaptive immune responses are increasingly needed.

Recently attention has been directed toward the utilization of nanomaterials as a part of vaccine formulation as the following: (1) delivery vehicles, (2) vaccine adjuvant, (3) increase of the sparing effect, (4) targeted delivery, (5) stabilization, and (6) slow release. Attention has also been directed toward manomaterials, modified to trigger specific immune responses, liposomes and lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, inorganic nanoparticles, virus-like particles, self-assembled proteins, and other nanoparticles including carbon-based nanoparticles (carbon nanotubes and graphenes). The modification of such nanomaterials is known to provide a functional and stable interface for different applications for vaccination.

In this Special Issue, entitled ‘Nanoparticles to Improve the Efficacy of Vaccines’, we would like to bring the reader’s attention to advanced platforms and technologies for vaccination using nanomaterials to achieve the best outcomes in terms of the efficacy of vaccinations and immunological memory.

Prof. Dr. Chong-Su Cho
Prof. Dr. Cheol-Heui Yun
Guest Editors

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Keywords

  • Vaccine
  • Nanoparticle
  • Nanotechnology
  • Adjuvant
  • Nanovaccinology
  • Polymeric vaccine
  • Immune cell targeting
  • Peptide vaccine
  • DNA vaccine

Published Papers (10 papers)

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Editorial

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4 pages, 177 KiB  
Editorial
Nanoparticles to Improve the Efficacy of Vaccines
by Cheol-Heui Yun and Chong-Su Cho
Pharmaceutics 2020, 12(5), 418; https://doi.org/10.3390/pharmaceutics12050418 - 02 May 2020
Cited by 7 | Viewed by 2021
Abstract
This editorial aims to summarize the nine scientific papers that contributed to the Special Issue entitled ‘Nanoparticles to Improve the Efficacy of Vaccines’. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)

Research

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18 pages, 3351 KiB  
Article
Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant
by Hyeong-Jun Park, Hae Li Ko, Dong-Hoon Won, Da-Bin Hwang, Yoo-Sub Shin, Hye-Won Kwak, Hye-Jung Kim, Jun-Won Yun and Jae-Hwan Nam
Pharmaceutics 2019, 11(9), 464; https://doi.org/10.3390/pharmaceutics11090464 - 07 Sep 2019
Cited by 10 | Viewed by 3849
Abstract
Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we [...] Read more.
Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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12 pages, 4018 KiB  
Article
Influenza Virus-Like Particles Presenting both Toxoplasma gondii ROP4 and ROP13 Enhance Protection against T. gondii Infection
by Hae-Ji Kang, Su-Hwa Lee, Min-Ju Kim, Ki-Back Chu, Dong-Hun Lee, Manika Chopra, Hyo-Jick Choi, Hyunwoo Park, Hui Jin and Fu-Shi Quan
Pharmaceutics 2019, 11(7), 342; https://doi.org/10.3390/pharmaceutics11070342 - 16 Jul 2019
Cited by 20 | Viewed by 3644
Abstract
Rhoptry organelle proteins (ROPs) secreted by Toxoplasma gondii (T. gondii) play a critical role during parasite invasion into host cells. In this study, virus-like particles (VLPs) vaccines containing ROP4 and/or ROP13 together with influenza M1 were generated. ROP4+ROP13 VLPs were produced [...] Read more.
Rhoptry organelle proteins (ROPs) secreted by Toxoplasma gondii (T. gondii) play a critical role during parasite invasion into host cells. In this study, virus-like particles (VLPs) vaccines containing ROP4 and/or ROP13 together with influenza M1 were generated. ROP4+ROP13 VLPs were produced by combining ROP4 VLPs with ROP13 VLPs, and ROP(4 + 13) VLPs by co-infecting insect cells with recombinant baculovirus expressing ROP4 or ROP13. Mice intranasally immunized with ROP(4 + 13) VLPs showed significantly higher levels of IgG, IgG1, IgG2a and IgA antibody responses in sera compared to ROP4+ROP13VLPs. Upon challenge infection by oral route, mice immunized with ROP(4 + 13) VLPs elicited higher levels of IgG and IgA antibody responses in fecal, urine, intestine and vaginal samples as well as CD4+ T, CD8+ T cells, and germinal center B cell responses compared to other type of vaccines, ROP4 VLPs, ROP13 VLPs, and ROP4+ROP13 VLPs. ROP(4 + 13) VLPs vaccination showed a significant decrease in the size and number of cyst in the brain and less body weight loss compared to combination ROP4+ROP13 VLPs upon challenge infection with T. gondii ME49. These results indicated that the ROP(4 + 13) VLPs vaccination provided enhanced protection against T. gondii infection compared to ROP4+ROP13 VLPs, providing an important insight into vaccine design strategy for T. gondii VLPs vaccines. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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15 pages, 2912 KiB  
Article
Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
by Cornelia Barnowski, Nicole Kadzioch, Dominik Damm, Huimin Yan and Vladimir Temchura
Pharmaceutics 2019, 11(5), 204; https://doi.org/10.3390/pharmaceutics11050204 - 01 May 2019
Cited by 14 | Viewed by 4108
Abstract
The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is [...] Read more.
The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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Review

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29 pages, 5900 KiB  
Review
Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies
by Michael Lim, Abu Zayed Md Badruddoza, Jannatul Firdous, Mohammad Azad, Adnan Mannan, Taslim Ahmed Al-Hilal, Chong-Su Cho and Mohammad Ariful Islam
Pharmaceutics 2020, 12(1), 30; https://doi.org/10.3390/pharmaceutics12010030 - 01 Jan 2020
Cited by 80 | Viewed by 10298
Abstract
DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide [...] Read more.
DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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21 pages, 2714 KiB  
Review
The Role of Nanovaccine in Cross-Presentation of Antigen-Presenting Cells for the Activation of CD8+ T Cell Responses
by Cheol Gyun Kim, Yoon-Chul Kye and Cheol-Heui Yun
Pharmaceutics 2019, 11(11), 612; https://doi.org/10.3390/pharmaceutics11110612 - 15 Nov 2019
Cited by 56 | Viewed by 5981
Abstract
Explosive growth in nanotechnology has merged with vaccine development in the battle against diseases caused by bacterial or viral infections and malignant tumors. Due to physicochemical characteristics including size, viscosity, density and electrostatic properties, nanomaterials have been applied to various vaccination strategies. Nanovaccines, [...] Read more.
Explosive growth in nanotechnology has merged with vaccine development in the battle against diseases caused by bacterial or viral infections and malignant tumors. Due to physicochemical characteristics including size, viscosity, density and electrostatic properties, nanomaterials have been applied to various vaccination strategies. Nanovaccines, as they are called, have been the subject of many studies, including review papers from a material science point of view, although a mode of action based on a biological and immunological understanding has yet to emerge. In this review, we discuss nanovaccines in terms of CD8+ T cell responses, which are essential for antiviral and anticancer therapies. We focus mainly on the role and mechanism, with particular attention to the functional aspects, of nanovaccines in inducing cross-presentation, an unconventional type of antigen-presentation that activates CD8+ T cells upon administration of exogenous antigens, in dendritic cells followed by activation of antigen-specific CD8+ T cell responses. Two major intracellular mechanisms that nanovaccines harness for cross-presentation are described; one is endosomal swelling and rupture, and the other is membrane fusion. Both processes eventually allow exogenous vaccine antigens to be exported from phagosomes to the cytosol followed by loading on major histocompatibility complex class I, triggering clonal expansion of CD8+ T cells. Advancement of nanotechnology with an enhanced understanding of how nanovaccines work will contribute to the design of more effective and safer nanovaccines. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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27 pages, 5114 KiB  
Review
Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials
by Veena Vijayan, Adityanarayan Mohapatra, Saji Uthaman and In-Kyu Park
Pharmaceutics 2019, 11(10), 534; https://doi.org/10.3390/pharmaceutics11100534 - 14 Oct 2019
Cited by 75 | Viewed by 7868
Abstract
The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable [...] Read more.
The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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20 pages, 1918 KiB  
Review
Application of ZnO-Based Nanocomposites for Vaccines and Cancer Immunotherapy
by Prashant Sharma, Na-Yoon Jang, Jae-Won Lee, Bum Chul Park, Young Keun Kim and Nam-Hyuk Cho
Pharmaceutics 2019, 11(10), 493; https://doi.org/10.3390/pharmaceutics11100493 - 26 Sep 2019
Cited by 34 | Viewed by 4774
Abstract
Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in [...] Read more.
Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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16 pages, 1705 KiB  
Review
Norovirus Capsid Protein-Derived Nanoparticles and Polymers as Versatile Platforms for Antigen Presentation and Vaccine Development
by Ming Tan and Xi Jiang
Pharmaceutics 2019, 11(9), 472; https://doi.org/10.3390/pharmaceutics11090472 - 12 Sep 2019
Cited by 22 | Viewed by 4739
Abstract
Major viral structural proteins interact homotypically and/or heterotypically, self-assembling into polyvalent viral capsids that usually elicit strong host immune responses. By taking advantage of such intrinsic features of norovirus capsids, two subviral nanoparticles, 60-valent S60 and 24-valent P24 nanoparticles, as well [...] Read more.
Major viral structural proteins interact homotypically and/or heterotypically, self-assembling into polyvalent viral capsids that usually elicit strong host immune responses. By taking advantage of such intrinsic features of norovirus capsids, two subviral nanoparticles, 60-valent S60 and 24-valent P24 nanoparticles, as well as various polymers, have been generated through bioengineering norovirus capsid shell (S) and protruding (P) domains, respectively. These nanoparticles and polymers are easily produced, highly stable, and extremely immunogenic, making them ideal vaccine candidates against noroviruses. In addition, they serve as multifunctional platforms to display foreign antigens, self-assembling into chimeric nanoparticles or polymers as vaccines against different pathogens and illnesses. Several chimeric S60 and P24 nanoparticles, as well as P domain-derived polymers, carrying different foreign antigens, have been created and demonstrated to be promising vaccine candidates against corresponding pathogens in preclinical animal studies, warranting their further development into useful vaccines. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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22 pages, 1379 KiB  
Review
Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies
by Rossella Sartorius, Luciana D’Apice, Antonella Prisco and Piergiuseppe De Berardinis
Pharmaceutics 2019, 11(9), 437; https://doi.org/10.3390/pharmaceutics11090437 - 01 Sep 2019
Cited by 29 | Viewed by 5570
Abstract
The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other [...] Read more.
The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, our laboratory focused its efforts in the study of antigen delivery strategies based on the filamentous bacteriophage ‘fd’, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses. We showed that fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently, we described the display of immunologically active lipids. In this review, we will provide an overview of the reported applications of the bacteriophage carriers and describe the advantages of exploiting this technology for delivery strategies. Full article
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
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