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Advances in the Use of Nanoparticles for Vaccine Platform Development

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Adjuvants".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 17801

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Prof. Dr. Imran Saleem

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School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
Interests: nanomedicine; nanoparticle toxicology; nanocarriers for pulmonary/nasal delivery (small molecules and macromolecules/vaccines); smart responsive nanocarriers
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Vaccination has been successful in the prevention, management, and treatment of communicable and some non-communicable diseases worldwide. With the greater understanding of immunology and advancements in molecular biology, the development of new vaccine candidates, such as nucleic acids (mRNA/DNA), or the incorporation of only certain components of pathogens (subunit vaccines) have resulted in more effective vaccines inducing specific immune responses, with reduced side effects. However, the new-generation vaccines also induce lower immunogenicity. Hence, nanoparticle-based formulations, such as polymeric, virosomes, and lipid nanoparticles, help in the induction of sufficient immune responses. These nanoparticle vaccine platform delivery systems protect vaccine candidates, improve stability, prevent degradation, and offer adjuvant properties enhancing immunogenicity and targeting antigen presenting cells (APCs). Furthermore, they help in eliciting innate, humoral, cellular, or mucosal immune response and can be administered through various routes. As we develop these nanoparticle-based vaccine delivery systems, there are also advancements in the methods of reproducible and scalable manufacture. Moreover, activation of dendritic cells, tumor immunotherapy, and use of biomimetic nanoparticles open new possibilities for the fight against infectious diseases, cancer, and other complex diseases.

This Special Issue welcomes original research and review articles focusing on the preclinical and clinical development of advanced nanoparticle delivery systems composed of liposomes and lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, inorganic nanoparticles, virus-like particles, self-assembled proteins, biomimetic nanoparticles, and other nanoparticles, including carbon-based nanoparticles (carbon nanotubes and graphenes) to trigger specific immune responses and immunological memory for human and veterinary use.

Prof. Dr. Imran Saleem
Guest Editor

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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.

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Keywords

nanoparticles
vaccine
immunotherapy
subunit vaccine
RNA vaccine
adjuvant
nanotechnology

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Published Papers (8 papers)

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Research

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19 pages, 1650 KiB

Open AccessArticle

Evaluating Nanoparticulate Vaccine Formulations for Effective Antigen Presentation and T-Cell Proliferation Using an In Vitro Overlay Assay

by Dedeepya Pasupuleti, Priyal Bagwe, Amarae Ferguson, Mohammad N. Uddin, Martin J. D’Souza and Susu M. Zughaier

Vaccines 2024, 12(9), 1049; https://doi.org/10.3390/vaccines12091049 - 13 Sep 2024

Viewed by 953

Abstract

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates’ ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay’s effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel^® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay’s potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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20 pages, 6664 KiB

Open AccessArticle

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model

by Sarthak Shah, Parth Patel, Amarae Ferguson, Priyal Bagwe, Akanksha Kale, Emmanuel Adediran, Revanth Singh, Tanisha Arte, Dedeepya Pasupuleti, Mohammad N. Uddin and Martin D’Souza

Vaccines 2024, 12(7), 720; https://doi.org/10.3390/vaccines12070720 - 28 Jun 2024

Viewed by 1306

Abstract

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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14 pages, 1374 KiB

Open AccessCommunication

Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice

by Srinivasa Reddy Bonam, Nicholas C. Hazell, Mano Joseph Mathew, Yuejin Liang, Xuxiang Zhang, Zhi Wei, Mohamad-Gabriel Alameh, Drew Weissman and Haitao Hu

Vaccines 2024, 12(5), 543; https://doi.org/10.3390/vaccines12050543 - 15 May 2024

Cited by 1 | Viewed by 2832

Abstract

The COVID-19 pandemic has raised the standard regarding the current vaccine development pace, as several messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines have proved their ability to induce strong immunogenicity and protective efficacy. We developed 1-methylpseudouridine-containing mRNA-LNP vaccines, expressing either the more conserved SARS-CoV-2 nucleoprotein (mRNA-N) or spike protein (mRNA-S), both based on the prototypic viral sequences. When combining both mRNA-S and mRNA-N together (mRNA-S+N), the vaccine showed high immunogenicity and broad protection against different SARS-CoV-2 variants, including wildtype, Delta, BA.1, BA.5, and BQ.1. To better understand the mechanisms behind this broad protection obtained by mRNA-S+N, we analyzed innate and adaptive immune parameters following vaccination in mice. Compared to either mRNA-S or mRNA-N alone, mice vaccinated with mRNA-S+N exhibited an increase in the innate immune response, as depicted by the higher cytokine (IL-6 and chemokine (MCP-1) levels. In addition, lymph node immunophenotyping showed the maturation and activation of dendritic cells and natural killer cells, respectively. To understand the adaptive immune response, RNA-Seq analyses of the lung and spleen samples of the vaccinated mice were performed in parallel and revealed a stronger immune gene-expression profile in the lung than that in the spleen. Compared to mRNA-S alone, mRNA-S+N vaccination elicited higher levels of expression for genes involved in multiple immune pathways, including T cells, cytokine signaling, antigen presentation, B cells, and innate immunity. Together, our studies provide immunological insights into the mechanisms of broad protection conferred by dual mRNA vaccination against SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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20 pages, 1821 KiB

Open AccessArticle

Characterization of the Efficacy of a Split Swine Influenza A Virus Nasal Vaccine Formulated with a Nanoparticle/STING Agonist Combination Adjuvant in Conventional Pigs

by Veerupaxagouda Patil, Juan F. Hernandez-Franco, Ganesh Yadagiri, Dina Bugybayeva, Sara Dolatyabi, Ninoshkaly Feliciano-Ruiz, Jennifer Schrock, Raksha Suresh, Juliette Hanson, Hadi Yassine, Harm HogenEsch and Gourapura J. Renukaradhya

Vaccines 2023, 11(11), 1707; https://doi.org/10.3390/vaccines11111707 - 10 Nov 2023

Cited by 1 | Viewed by 2011

Abstract

Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Intranasal (IN) vaccination has the potential to reduce flu infection. We investigated the efficacy of split SwIAV H1N2 antigens adsorbed with a plant origin nanoparticle adjuvant [Nano11–SwIAV] or in combination with a STING agonist ADU-S100 [NanoS100–SwIAV]. Conventional pigs were vaccinated via IN and challenged with a heterologous SwIAV H1N1-OH7 or 2009 H1N1 pandemic virus. Immunologically, in NanoS100–SwIAV vaccinates, we observed enhanced frequencies of activated monocytes in the blood of the pandemic virus challenged animals and in tracheobronchial lymph nodes (TBLN) of H1N1-OH7 challenged animals. In both groups of the virus challenged pigs, increased frequencies of IL-17A⁺ and CD49d⁺IL-17A⁺ cytotoxic lymphocytes were observed in Nano11–SwIAV vaccinates in the draining TBLN. Enhanced frequency of CD49d⁺IFNγ⁺ CTLs in the TBLN and blood of both the Nano11-based SwIAV vaccinates was observed. Animals vaccinated with both Nano11-based vaccines had upregulated cross-reactive secretory IgA in the lungs and serum IgG against heterologous and heterosubtypic viruses. However, in NanoS100–SwIAV vaccinates, a slight early reduction in the H1N1 pandemic virus and a late reduction in the SwIAV H1N1-OH7 load in the nasal passages were detected. Hence, despite vast genetic differences between the vaccine and both the challenge viruses, IN vaccination with NanoS100–SwIAV induced antigen-specific moderate levels of cross-protective immune responses. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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14 pages, 3296 KiB

Open AccessArticle

Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens

by Moustafa T. Mabrouk, Asmaa A. Zidan, Nihal Aly, Mostafa T. Mohammed, Fadi Ghantous, Michael S. Seaman, Jonathan F. Lovell and Mahmoud L. Nasr

Vaccines 2023, 11(11), 1655; https://doi.org/10.3390/vaccines11111655 - 28 Oct 2023

Cited by 2 | Viewed by 2369

Abstract

The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin–phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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16 pages, 2996 KiB

Open AccessArticle

Synthesis and Optimization of Next-Generation Low-Molecular-Weight Pentablock Copolymer Nanoadjuvants

by Alaric C. Siddoway, Brianna M. White, Balaji Narasimhan and Surya K. Mallapragada

Vaccines 2023, 11(10), 1572; https://doi.org/10.3390/vaccines11101572 - 9 Oct 2023

Cited by 1 | Viewed by 1487

Abstract

Polymeric nanomaterials such as Pluronic^®-based pentablock copolymers offer important advantages over traditional vaccine adjuvants and have been increasingly investigated in an effort to develop more efficacious vaccines. Previous work with Pluronic^® F127-based pentablock copolymers, functionalized with poly(diethyl aminoethyl methacrylate) (PDEAEM) blocks, demonstrated adjuvant capabilities through the antigen presentation and crosslinking of B cell receptors. In this work, we describe the synthesis and optimization of a new family of low-molecular-weight Pluronic^®-based pentablock copolymer nanoadjuvants with high biocompatibility and improved adjuvanticity at low doses. We synthesized low-molecular-weight Pluronic^® P123-based pentablock copolymers with PDEAEM blocks and investigated the relationship between polymer concentration, micellar size, and zeta potential, and measured the release kinetics of a model antigen, ovalbumin, from these nanomaterials. The Pluronic^® P123-based pentablock copolymer nanoadjuvants showed higher biocompatibility than the first-generation Pluronic^® F127-based pentablock copolymer nanoadjuvants. We assessed the adjuvant capabilities of the ovalbumin-containing Pluronic^® P123-based pentablock copolymer-based nanovaccines in mice, and showed that animals immunized with these nanovaccines elicited high antibody titers, even when used at significantly reduced doses compared to Pluronic^® F127-based pentablock copolymers. Collectively, these studies demonstrate the synthesis, self-assembly, biocompatibility, and adjuvant properties of a new family of low-molecular-weight Pluronic^® P123-based pentablock copolymer nanomaterials, with the added benefits of more efficient renal clearance, high biocompatibility, and enhanced adjuvanticity at low polymer concentrations. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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19 pages, 3643 KiB

Open AccessArticle

Combined Live Oral Priming and Intramuscular Boosting Regimen with Rotarix^® and a Nanoparticle-Based Trivalent Rotavirus Vaccine Evaluated in Gnotobiotic Pig Models of G4P[6] and G1P[8] Human Rotavirus Infection

by Casey Hensley, Charlotte Nyblade, Peng Zhou, Viviana Parreño, Ashwin Ramesh, Annie Frazier, Maggie Frazier, Sarah Garrison, Ariana Fantasia-Davis, Ruiqing Cai, Peng-Wei Huang, Ming Xia, Ming Tan and Lijuan Yuan

Vaccines 2023, 11(5), 927; https://doi.org/10.3390/vaccines11050927 - 2 May 2023

Cited by 2 | Viewed by 2600

Abstract

Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S₆₀-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix^® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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Review

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22 pages, 1379 KiB

Open AccessReview

An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer

by Yang Lin, Xuehua Chen, Ke Wang, Li Liang and Hongxia Zhang

Vaccines 2024, 12(7), 727; https://doi.org/10.3390/vaccines12070727 - 29 Jun 2024

Cited by 2 | Viewed by 2426

Abstract

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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