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Pharmaceutics
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Nanovaccine Fight against Infectious Diseases
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Nanovaccine Fight against Infectious Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 August 2023) | Viewed by 21509

Special Issue Editor

Dr. Yimei Jia

E-Mail Website
Guest Editor
Human Health Therapeutics, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
Interests: nanotechnology; nanovaccine; adjuvant; nucleic acid; vaccine delivery; biomaterial engineering; targeting; immune response; vaccine formulation; vaccine stability

Special Issue Information

Dear Colleagues,

Infectious diseases are the leading causes of morbidity and mortality. Despite great advances in the field of vaccination, novel and effective vaccines are still needed to prevent diseases such as malaria, tuberculosis, and human immunodeficiency virus, among others. In addition, vaccine development for the immune-compromised population, and for those with pre-existing medical conditions, remains a major challenge. Furthermore, some existing vaccines have unmet needs such as engagement of adaptive immune system, effective control of cytokine release, cold chain handling and storage, and the requirement of multiple administrations.

Nanotechnology-enabled approaches have emerged as promising strategies to overcome the limitations of traditional vaccines and demonstrated tangible impacts on global health. For example, lipid nanoparticles delivered an mRNA vaccine to tackle the COVID-19 pandemic. Emerging nanomaterials (natural or synthetic), including virus-like particles, liposomes, polymeric nanoparticles (NP), self-assembly proteins, or peptide-based NPs have received considerable attention over the past decade as potential carriers to deliver vaccine antigens and adjuvants. Because of their advantages such as enhanced antigen stability, tissue and/or cell targeted delivery, sustained antigen release, and engineering capability onto NP surface, the design of a nanoparticle-based vaccine (nanovaccine) allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development.

The topics discussed in this Special Issue include, but are not limited to:

  • Nanotechnological approaches employed in the areas of prevention of infectious diseases;
  • The design of nanovaccine formulations and processes;
  • Tissue and cell-specific delivery of nanovaccines;
  • Antigen presentation;
  • Stimulation of innate and/or adaptive immune responses;
  • Immunology mechanisms;
  • Nanovaccines for immunopathogenesis;
  • Non-viral vectors for vaccine, vaccine adjuvants, and immunomodulators;
  • Prophylactic vaccines, therapeutic vaccines, and vaccines in bioterrorism.

I look forward to receiving your contributions.

Dr. Yimei Jia
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. Pharmaceutics 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 2900 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

  • nanotechnology
  • nanovaccine
  • vaccine adjuvant
  • vaccine delivery
  • immune responses
  • infection disease
  • nucleic acid
  • vaccine targeting
  • biomaterial engineering
  • vaccine stability

Published Papers (8 papers)

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Research

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18 pages, 3157 KiB  
Article
Lipid–Polymer Hybrid Nanoparticles for mRNA Delivery to Dendritic Cells: Impact of Lipid Composition on Performance in Different Media
by Lena Kliesch, Simon Delandre, Aljoscha Gabelmann, Marcus Koch, Kai Schulze, Carlos A. Guzmán, Brigitta Loretz and Claus-Michael Lehr
Pharmaceutics 2022, 14(12), 2675; https://doi.org/10.3390/pharmaceutics14122675 - 01 Dec 2022
Cited by 2 | Viewed by 2320
Abstract
To combine the excellent transfection properties of lipids with the high stability of polymeric nanoparticles, we designed a hybrid system with a polymeric core surrounded by a shell of different lipids. The aim is to use this technology for skin vaccination purposes where [...] Read more.
To combine the excellent transfection properties of lipids with the high stability of polymeric nanoparticles, we designed a hybrid system with a polymeric core surrounded by a shell of different lipids. The aim is to use this technology for skin vaccination purposes where the transfection of dendritic cells is crucial. Based on a carrier made of PLGA and the positively charged lipid DOTMA, we prepared a panel of nanocarriers with increasing amounts of the zwitterionic phospholipid DOPE in the lipid layer to improve their cell tolerability. We selected a nomenclature accordingly with numbers in brackets to represent the used mol% of DOPE and DOTMA in the lipid layer, respectively. We loaded mRNA onto the surface and assessed the mRNA binding efficacy and the degree of protection against RNases. We investigated the influence of the lipid composition on the toxicity, uptake and transfection in the dendritic cell line DC 2.4 challenging the formulations with different medium supplements like fetal calf serum (FCS) and salts. After selecting the most promising candidate, we performed an immune stimulation assay with primary mouse derived dendritic cells. The experiments showed that all tested lipid–polymer nanoparticles (LPNs) have comparable hydrodynamic parameters with sizes between 200 and 250 nm and are able to bind mRNA electrostatically due to their positive zetapotential (20–40 mV for most formulations). The more of DOPE we add, the more free mRNA we find and the better the cellular uptake reaching approx. 100% for LPN(60/40)–LPN(90/10). This applies for all tested formulations leading to LPN(70/30) with the best performance, in terms of 67% of live cells with protein expression. In that case, the supplements of the medium did not influence the transfection efficacy (56% vs. 67% (suppl. medium) for live cells and 63% vs. 71% in total population). We finally confirmed this finding using mouse derived primary immune cells. We can conclude that a certain amount of DOTMA in the lipid coating of the polymer core is essential for complexation of the mRNA, but the zwitterionic phospholipid DOPE is also important for the particles’ performance in supplemented media. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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14 pages, 3167 KiB  
Article
Evaluation of Adjuvant Activity and Bio-Distribution of Archaeosomes Prepared Using Microfluidic Technology
by Yimei Jia, Gerard Agbayani, Vandana Chandan, Umar Iqbal, Renu Dudani, Hui Qian, Zygmunt Jakubek, Kenneth Chan, Blair Harrison, Lise Deschatelets, Bassel Akache and Michael J. McCluskie
Pharmaceutics 2022, 14(11), 2291; https://doi.org/10.3390/pharmaceutics14112291 - 26 Oct 2022
Cited by 3 | Viewed by 1682
Abstract
Archaeosomes, composed of sulfated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. They have classically been prepared using a thin-film hydration method with an average particle size of 100–200 [...] Read more.
Archaeosomes, composed of sulfated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. They have classically been prepared using a thin-film hydration method with an average particle size of 100–200 nm. In this study, we developed methods to generate SLA archaeosomes at different sizes, i.e., 30 nm and 100 nm, via microfluidic mixing technology and evaluated their physicochemical characteristics, as well as adjuvant activity and in vivo biodistribution in mice. Archaeosomes, prepared using thin-film and microfluidic mixing techniques, had similar nanostructures and physicochemical characteristics, with both appearing stable during the course of this study when stored at 4 °C or 37 °C. They also demonstrated similar adjuvant activity when admixed with ovalbumin antigen and used to immunize mice, generating equivalent antigen-specific immune responses. Archaeosomes, labeled with CellVueTM NIR815, had an equivalent biodistribution with both sizes, namely the highest signal at the injection site at 24 h post injection, followed by liver, spleen and inguinal lymph node. The presence of SLA archaeosomes of either size helped to retain OVA antigen (OVA-Cy5.5) longer at the injection site than unadjuvanted OVA. Overall, archaeosomes of two sizes (30 nm and 100 nm) prepared using microfluidic mixing maintained similar physicochemical properties, adjuvant activity and biodistribution of antigen, in comparison to those compared by the conventional thin film hydration method. This suggests that microfluidics based approaches could be applied to generate consistently sized archaeosomes for use as a vaccine adjuvant. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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22 pages, 3077 KiB  
Article
Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine
by Kristopher K. Short, Stephanie K. Lathrop, Clara J. Davison, Haley A. Partlow, Johnathan A. Kaiser, Rebekah D. Tee, Elizabeth B. Lorentz, Jay T. Evans and David J. Burkhart
Pharmaceutics 2022, 14(7), 1455; https://doi.org/10.3390/pharmaceutics14071455 - 12 Jul 2022
Cited by 3 | Viewed by 2885
Abstract
A diversity of vaccines is necessary to reduce the mortality and morbidity of SARS-CoV-2. Vaccines must be efficacious, easy to manufacture, and stable within the existing cold chain to improve their availability around the world. Recombinant protein subunit vaccines adjuvanted with squalene-based emulsions [...] Read more.
A diversity of vaccines is necessary to reduce the mortality and morbidity of SARS-CoV-2. Vaccines must be efficacious, easy to manufacture, and stable within the existing cold chain to improve their availability around the world. Recombinant protein subunit vaccines adjuvanted with squalene-based emulsions such as AS03™ and MF59™ have a long and robust history of safe, efficacious use with straightforward production and distribution. Here, subunit vaccines were made with squalene-based emulsions containing novel, synthetic toll-like receptor (TLR) agonists, INI-2002 (TLR4 agonist) and INI-4001 (TLR7/8 agonist), using the recombinant receptor-binding domain (RBD) of SARS-CoV-2 S protein as an antigen. The addition of the TLR4 and TLR7/8 agonists, alone or in combination, maintained the formulation characteristics of squalene-based emulsions, including a sterile filterable droplet size (<220 nm), high homogeneity, and colloidal stability after months of storage at 4, 25, and 40 °C. Furthermore, the addition of the TLR agonists skewed the immune response from Th2 towards Th1 in immunized C57BL/6 mice, resulting in an increased production of IgG2c antibodies and a lower antigen-specific production of IL-5 with a higher production of IFNγ by lymphocytes. As such, incorporating TLR4 and TLR7/8 agonists into emulsions leveraged the desirable formulation and stability characteristics of emulsions and can induce Th1-type humoral and cell-mediated immune responses to combat the continued threat of SARS-CoV-2. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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19 pages, 3992 KiB  
Article
Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes
by Dominik Damm, Ehsan Suleiman, Hannah Theobald, Jannik T. Wagner, Mirjam Batzoni, Bianca Ahlfeld (née Kohlhauser), Bernd Walkenfort, Jens-Christian Albrecht, Jidnyasa Ingale, Lifei Yang, Mike Hasenberg, Richard T. Wyatt, Karola Vorauer-Uhl, Klaus Überla and Vladimir Temchura
Pharmaceutics 2022, 14(7), 1385; https://doi.org/10.3390/pharmaceutics14071385 - 30 Jun 2022
Cited by 3 | Viewed by 1961
Abstract
Functionalization of experimental HIV-1 virus-like particle vaccines with heterologous T helper epitopes (T helper VLPs) can modulate the humoral immune response via intrastructural help (ISH). Current advances in the conjugation of native-like HIV-1 envelope trimers (Env) onto liposomes and encapsulation of peptide epitopes [...] Read more.
Functionalization of experimental HIV-1 virus-like particle vaccines with heterologous T helper epitopes (T helper VLPs) can modulate the humoral immune response via intrastructural help (ISH). Current advances in the conjugation of native-like HIV-1 envelope trimers (Env) onto liposomes and encapsulation of peptide epitopes into these nanoparticles renders this GMP-scalable liposomal platform a feasible alternative to VLP-based vaccines. In this study, we designed and analyzed customizable Env-conjugated T helper liposomes. First, we passively encapsulated T helper peptides into a well-characterized liposome formulation displaying a dense array of Env trimers on the surface. We confirmed the closed pre-fusion state of the coupled Env trimers by immunogold staining with conformation-specific antibodies. These peptide-loaded Env-liposome conjugates efficiently activated Env-specific B cells, which further induced proliferation of CD4+ T cells by presentation of liposome-derived peptides on MHC-II molecules. The peptide encapsulation process was then quantitatively improved by an electrostatically driven approach using an overall anionic lipid formulation. We demonstrated that peptides delivered by liposomes were presented by DCs in secondary lymphoid organs after intramuscular immunization of mice. UFO (uncleaved prefusion optimized) Env trimers were covalently coupled to peptide-loaded anionic liposomes by His-tag/NTA(Ni) interactions and EDC/Sulfo-NHS crosslinking. EM imaging revealed a moderately dense array of well-folded Env trimers on the liposomal surface. The conformation was verified by liposomal surface FACS. Furthermore, anionic Env-coupled T helper liposomes effectively induced Env-specific B cell activation and proliferation in a comparable range to T helper VLPs. Taken together, we demonstrated that T helper VLPs can be substituted with customizable and GMP-scalable liposomal nanoparticles as a perspective for future preclinical and clinical HIV vaccine applications. The functional nanoparticle characterization assays shown in this study can be applied to other systems of synthetic nanoparticles delivering antigens derived from various pathogens. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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14 pages, 2446 KiB  
Article
Freeze-Drying of a Capsid Virus-like Particle-Based Platform Allows Stable Storage of Vaccines at Ambient Temperature
by Kara-Lee Aves, Christoph M. Janitzek, Cyrielle E. Fougeroux, Thor G. Theander and Adam F. Sander
Pharmaceutics 2022, 14(6), 1301; https://doi.org/10.3390/pharmaceutics14061301 - 18 Jun 2022
Cited by 3 | Viewed by 2490
Abstract
The requirement of an undisrupted cold chain during vaccine distribution is a major economic and logistical challenge limiting global vaccine access. Modular, nanoparticle-based platforms are expected to play an increasingly important role in the development of the next-generation vaccines. However, as with most [...] Read more.
The requirement of an undisrupted cold chain during vaccine distribution is a major economic and logistical challenge limiting global vaccine access. Modular, nanoparticle-based platforms are expected to play an increasingly important role in the development of the next-generation vaccines. However, as with most vaccines, they are dependent on the cold chain in order to maintain stability and efficacy. Therefore, there is a pressing need to develop thermostable formulations that can be stored at ambient temperature for extended periods without the loss of vaccine efficacy. Here, we investigate the compatibility of the Tag/Catcher AP205 capsid virus-like particle (cVLP) vaccine platform with the freeze-drying process. Tag/Catcher cVLPs can be freeze-dried under diverse buffer and excipient conditions while maintaining their original biophysical properties. Additionally, we show that for two model cVLP vaccines, including a clinically tested SARS-CoV-2 vaccine, freeze-drying results in a product that once reconstituted retains the structural integrity and immunogenicity of the original material, even following storage under accelerated heat stress conditions. Furthermore, the freeze-dried SARS-CoV-2 cVLP vaccine is stable for up to 6 months at ambient temperature. Our study offers a potential solution to overcome the current limitations associated with the cold chain and may help minimize the need for low-temperature storage. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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20 pages, 1559 KiB  
Article
Peptide-Based Vaccine against SARS-CoV-2: Peptide Antigen Discovery and Screening of Adjuvant Systems
by Ahmed O. Shalash, Armira Azuar, Harrison Y. R. Madge, Naphak Modhiran, Alberto A. Amarilla, Benjamin Liang, Alexander A. Khromykh, Waleed M. Hussein, Keith J. Chappell, Daniel Watterson, Paul R. Young, Mariusz Skwarczynski and Istvan Toth
Pharmaceutics 2022, 14(4), 856; https://doi.org/10.3390/pharmaceutics14040856 - 13 Apr 2022
Cited by 4 | Viewed by 2160
Abstract
The SARS-CoV-2 virus has caused a global crisis, resulting in 0.5 billion infections and over 6 million deaths as of March 2022. Fortunately, infection and hospitalization rates were curbed due to the rollout of DNA and mRNA vaccines. However, the efficacy of these [...] Read more.
The SARS-CoV-2 virus has caused a global crisis, resulting in 0.5 billion infections and over 6 million deaths as of March 2022. Fortunately, infection and hospitalization rates were curbed due to the rollout of DNA and mRNA vaccines. However, the efficacy of these vaccines significantly drops a few months post immunization, from 88% down to 47% in the case of the Pfizer BNT162 vaccine. The emergence of variant strains, especially delta and omicron, have also significantly reduced vaccine efficacy. We propose peptide vaccines as a potential solution to address the inadequacies of the current vaccines. Peptide vaccines can be easily modified to target emerging strains, have greater stability, and do not require cold-chain storage. We screened five peptide fragments (B1–B5) derived from the SARS-CoV-2 spike protein to identify neutralizing B-cell peptide antigens. We then investigated adjuvant systems for efficient stimulation of immune responses against the most promising peptide antigens, including liposomal formulations of polyleucine (L10) and polymethylacrylate (PMA), as well as classical adjuvants (CFA and MF59). Immune efficacy of formulations was evaluated using competitive ELISA, pseudovirion neutralization, and live virus neutralization assays. Unfortunately, peptide conjugation to L10 and PMA dramatically altered the secondary structure, resulting in low antibody neutralization efficacy. Of the peptides tested, only B3 administered with CFA or MF59 was highly immunogenic. Thus, a peptide vaccine relying on B3 may provide an attractive alternative to currently marketed vaccines. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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22 pages, 6813 KiB  
Article
Designing Stable Bacillus anthracis Antigens with a View to Recombinant Anthrax Vaccine Development
by Ekaterina M. Ryabchevskaya, Dmitriy L. Granovskiy, Ekaterina A. Evtushenko, Peter A. Ivanov, Olga A. Kondakova, Nikolai A. Nikitin and Olga V. Karpova
Pharmaceutics 2022, 14(4), 806; https://doi.org/10.3390/pharmaceutics14040806 - 06 Apr 2022
Cited by 5 | Viewed by 3687
Abstract
Anthrax is a disease caused by Bacillus anthracis that affects mammals, including humans. Recombinant B. anthracis protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability due to proteolysis and deamidation. Here, [...] Read more.
Anthrax is a disease caused by Bacillus anthracis that affects mammals, including humans. Recombinant B. anthracis protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability due to proteolysis and deamidation. Here, for the first time, two modification variants leading to full-size rPA stabilisation have been implemented simultaneously, through deamidation-prone asparagine residues substitution and by inactivation of proteolysis sites. Obtained modified rPA (rPA83m) has been demonstrated to be stable in various temperature conditions. Additionally, rPA1+2 containing PA domains I and II and rPA3+4 containing domains III and IV, including the same modifications, have been shown to be stable as well. These antigens can serve as the basis for a vaccine, since the protective properties of PA can be attributed to individual PA domains. The stability of each of three modified anthrax antigens has been considerably improved in compositions with tobacco mosaic virus-based spherical particles (SPs). rPA1+2/rPA3+4/rPA83m in compositions with SPs have maintained their antigenic specificity even after 40 days of incubation at +37 °C. Considering previously proven adjuvant properties and safety of SPs, their compositions with rPA83m/rPA1+2/rPA3+4 in any combinations might be suitable as a basis for new-generation anthrax vaccines. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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Review

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27 pages, 2508 KiB  
Review
Nanovaccines against Viral Infectious Diseases
by Wen Tzuen Heng, Jia Sheng Yew and Chit Laa Poh
Pharmaceutics 2022, 14(12), 2554; https://doi.org/10.3390/pharmaceutics14122554 - 22 Nov 2022
Cited by 7 | Viewed by 2802
Abstract
Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of [...] Read more.
Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed. Full article
(This article belongs to the Special Issue Nanovaccine Fight against Infectious Diseases)
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