Advance in Nanoparticles as Vaccine Adjuvants

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 17838

Special Issue Editors


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Guest Editor
Department of Biotechnology, INIA-CSIC, 28040 Madrid, Spain
Interests: viral immunology; innate immunity; adaptive immunity; adjuvants; vaccines; immune pathways; fish immunology; rhabdovirus; virus-host interaction; RNA virus; DNA virus
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Guest Editor
Faculty of Veterinary Medicine, Ludwig Maximilian University of Munich, 80539 München, Germany
Interests: veterinary sciences; viral immunology; virus pathogenesis; vaccines

Special Issue Information

Dear Colleagues,  

Remarkable efforts have been made to develop new and improved vaccines attending antigen’s nature and immune mechanisms involved. To obtain an appropriate humoral and cell-mediated immunity, risk-free and effective vaccines are needed against infectious diseases and tumoral processes. In the last years, nanoparticles have gained much interest in new vaccines generation since they can protect the antigen targets from premature proteolytic degradation, lead to a homogeneous uptake of antigens by immune cells, and facilitating their processing and presentation. Nanoparticles composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes.  This special issue aims to collect recent original research and reviews on nanoparticulate-loaded vaccines attain their nature, formulation, delivery, their safe and efficacy, and induced immune responses to accomplish efficient and long-lasting protection against infectious diseases and tumors. I look forward to receiving your contributions. 

Dr. Eduardo Gomez-Casado
Dr. Sohrab Ahmadivand
Guest Editors

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Keywords

  • nanoparticles
  • adjuvant
  • innate immune response
  • adaptive immune response
  • delivery
  • humoral and cellular mediated immunity
  • infectious diseases
  • tumors

Published Papers (8 papers)

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Research

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12 pages, 792 KiB  
Article
Polymeric Caffeic Acid Acts as an Antigen Delivery Carrier for Mucosal Vaccine Formulation by Forming a Complex with an Antigenic Protein
by Rui Tada, Yuzuho Nagai, Miki Ogasawara, Momoko Saito, Akihiro Ohshima, Daisuke Yamanaka, Jun Kunisawa, Yoshiyuki Adachi and Yoichi Negishi
Vaccines 2024, 12(5), 449; https://doi.org/10.3390/vaccines12050449 - 23 Apr 2024
Viewed by 756
Abstract
The development of mucosal vaccines, which can generate antigen-specific immune responses in both the systemic and mucosal compartments, has been recognized as an effective strategy for combating infectious diseases caused by pathogenic microbes. Our recent research has focused on creating a nasal vaccine [...] Read more.
The development of mucosal vaccines, which can generate antigen-specific immune responses in both the systemic and mucosal compartments, has been recognized as an effective strategy for combating infectious diseases caused by pathogenic microbes. Our recent research has focused on creating a nasal vaccine system in mice using enzymatically polymerized caffeic acid (pCA). However, we do not yet understand the molecular mechanisms by which pCA stimulates antigen-specific mucosal immune responses. In this study, we hypothesized that pCA might activate mucosal immunity at the site of administration based on our previous findings that pCA possesses immune-activating properties. However, contrary to our initial hypothesis, the intranasal administration of pCA did not enhance the expression of various genes involved in mucosal immune responses, including the enhancement of IgA responses. Therefore, we investigated whether pCA forms a complex with antigenic proteins and enhances antigen delivery to mucosal dendritic cells located in the lamina propria beneath the mucosal epithelial layer. Data from gel filtration chromatography indicated that pCA forms a complex with the antigenic protein ovalbumin (OVA). Furthermore, we examined the promotion of OVA delivery to nasal mucosal dendritic cells (mDCs) after the intranasal administration of pCA in combination with OVA and found that OVA uptake by mDCs was increased. Therefore, the data from gel filtration chromatography and flow cytometry imply that pCA enhances antigen-specific antibody production in both mucosal and systemic compartments by serving as an antigen-delivery vehicle. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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17 pages, 2919 KiB  
Article
Vaccination-Route-Dependent Adjuvanticity of Antigen-Carrying Nanoparticles for Enhanced Vaccine Efficacy
by Chaojun Song, Jinwei Hu, Yutao Liu, Yi Tian, Yupu Zhu, Jiayue Xi, Minxuan Cui, Xiaolei Wang, Bao-Zhong Zhang, Li Fan and Quan Li
Vaccines 2024, 12(2), 125; https://doi.org/10.3390/vaccines12020125 - 26 Jan 2024
Viewed by 1298
Abstract
Vaccination-route-dependent adjuvanticity was identified as being associated with the specific features of antigen-carrying nanoparticles (NPs) in the present work. Here, we demonstrated that the mechanical properties and the decomposability of NP adjuvants play key roles in determining the antigen accessibility and thus the [...] Read more.
Vaccination-route-dependent adjuvanticity was identified as being associated with the specific features of antigen-carrying nanoparticles (NPs) in the present work. Here, we demonstrated that the mechanical properties and the decomposability of NP adjuvants play key roles in determining the antigen accessibility and thus the overall vaccine efficacy in the immune system when different vaccination routes were employed. We showed that soft nano-vaccines were associated with more efficient antigen uptake when administering subcutaneous (S.C.) vaccination, while the slow decomposition of hard nano-vaccines promoted antigen uptake when intravenous (I.V.) vaccination was employed. In comparison to the clinically used aluminum (Alum) adjuvant, the NP adjuvants were found to stimulate both humoral and cellular immune responses efficiently, irrespective of the vaccination route. For vaccination via S.C. and I.V. alike, the NP-based vaccines show excellent protection for mice from Staphylococcus aureus (S. aureus) infection, and their survival rates are 100% after lethal challenge, being much superior to the clinically used Alum adjuvant. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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20 pages, 11158 KiB  
Article
A Thermal-Stable Protein Nanoparticle That Stimulates Long Lasting Humoral Immune Response
by Ten-Tsao Wong, Gunn-Guang Liou and Ming-Chung Kan
Vaccines 2023, 11(2), 426; https://doi.org/10.3390/vaccines11020426 - 13 Feb 2023
Cited by 2 | Viewed by 2075
Abstract
A thermally stable vaccine platform is considered the missing piece of vaccine technology. In this article, we reported the creation of a novel protein nanoparticle and assessed its ability to withstand extended high temperature incubation while stimulating a long-lasting humoral immune response. This [...] Read more.
A thermally stable vaccine platform is considered the missing piece of vaccine technology. In this article, we reported the creation of a novel protein nanoparticle and assessed its ability to withstand extended high temperature incubation while stimulating a long-lasting humoral immune response. This protein nanoparticle was assembled from a fusion protein composed of an amphipathic helical peptide derived from the M2 protein of the H5N1 influenza virus (AH3) and a superfolder green fluorescent protein (sfGFP). Its proposed structure was modeled according to transmission electronic microscope (TEM) images of protein nanoparticles. From this proposed protein model, we created a mutant with two gain-of-function mutations that work synergistically on particle stability. A protein nanoparticle assembled from this gain-of-function mutant is able to remove a hydrophobic patch from its surface. This gain-of-function mutant also contributes to the higher thermostability of protein nanoparticles and stimulates a long lasting humoral immune response after a single immunization. This assembled nanoparticle showed increasing particle stability at higher temperatures and salt concentrations. This novel protein nanoparticle may serve as a thermally-stable platform for vaccine development. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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13 pages, 1955 KiB  
Article
The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines
by Jieru Yang, Jennifer C. Boer, Mattaka Khongkow, Sarunya Phunpee, Zeinab G. Khalil, Sahra Bashiri, Cyril Deceneux, Georgia Goodchild, Waleed M. Hussein, Robert J. Capon, Uracha Ruktanonchai, Magdalena Plebanski, Istvan Toth and Mariusz Skwarczynski
Vaccines 2023, 11(2), 305; https://doi.org/10.3390/vaccines11020305 - 30 Jan 2023
Cited by 2 | Viewed by 1806
Abstract
Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number [...] Read more.
Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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18 pages, 3456 KiB  
Article
Immune Enhancement of Nanoparticle-Encapsulated Ginseng Stem-Leaf Saponins on Porcine Epidemic Diarrhea Virus Vaccine in Mice
by Fei Su, Lihua Xu, Yin Xue, Wei Xu, Junxing Li, Bin Yu, Shiyi Ye and Xiufang Yuan
Vaccines 2022, 10(11), 1810; https://doi.org/10.3390/vaccines10111810 - 27 Oct 2022
Cited by 5 | Viewed by 1848
Abstract
Porcine epidemic diarrhea virus (PEDV) causes severe enteric disease in pigs, particularly neonatal piglets. Current vaccines do not provide complete protection against PEDV. Ginseng stem-leaf saponins (GSLS), a promising oral adjuvant candidate, can improve intestinal immune responses in poultry and mice. However, its [...] Read more.
Porcine epidemic diarrhea virus (PEDV) causes severe enteric disease in pigs, particularly neonatal piglets. Current vaccines do not provide complete protection against PEDV. Ginseng stem-leaf saponins (GSLS), a promising oral adjuvant candidate, can improve intestinal immune responses in poultry and mice. However, its low stability limits further use. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable nanoparticle, has been widely used in biomedicine for stable and targeted drug delivery. In this study, we developed GSLS-PLGA nanoparticles (GSLS-NPs) and evaluated the mucosal adjuvant efficacy in vitro and in vivo. GSLS-NPs significantly enhanced antigen internalization and pro-inflammatory cytokine secretion by DC2.4 cells. Mice orally administered GSLS-NPs before intramuscular inoculation generated CD11b+CD8α and CD11bCD103+ dendritic cells in the spleen and draining mesenteric lymph nodes, respectively, which are the types mainly responsible for antigen presentation. Additionally, enhanced neutralizing and non-neutralizing antibody responses and expanded activities of specific effector and memory CD4+ and CD8+ T cells were also observed in mice immunized with PEDV vaccines plus GSLS-NPs compared to mice receiving the vaccines alone. Furthermore, GSLS-NPs showed a good safety profile and presented great advantages over GSLS aqueous solution. Collectively, our results highlight the potential of GSLS-NPs as a mucosal adjuvant and provide an attractive vaccination strategy for combatting PEDV. Further study is required to evaluate the efficacy of this mucosal adjuvant in swine. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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Review

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20 pages, 2277 KiB  
Review
Efficiency of Chitosan Nanocarriers in Vaccinology for Mucosal Immunization
by Salvatore Calogero Gaglio, Massimiliano Perduca, Donato Zipeto and Giuseppe Bardi
Vaccines 2023, 11(8), 1333; https://doi.org/10.3390/vaccines11081333 - 6 Aug 2023
Cited by 1 | Viewed by 1789
Abstract
The mucosal barrier constitutes a huge surface area, close to 40 m2 in humans, located mostly in the respiratory, gastrointestinal and urogenital tracts and ocular cavities. It plays a crucial role in tissue interactions with the microbiome, dietary antigens and other environmental [...] Read more.
The mucosal barrier constitutes a huge surface area, close to 40 m2 in humans, located mostly in the respiratory, gastrointestinal and urogenital tracts and ocular cavities. It plays a crucial role in tissue interactions with the microbiome, dietary antigens and other environmental materials. Effective vaccinations to achieve highly protective mucosal immunity are evolving strategies to counteract several serious diseases including tuberculosis, diphtheria, influenzae B, severe acute respiratory syndrome, Human Papilloma Virus infection and Acquired Immune Deficiency Syndrome. Interestingly, one of the reasons behind the rapid spread of severe acute respiratory syndrome coronavirus 2 variants has been the weakness of local immunization at the level of the respiratory mucosa. Mucosal vaccines can outperform parenteral vaccination as they specifically elicit protective mucosal immune responses blocking infection and transmission. In this scenario, chitosan-based nanovaccines are promising adjuvants-carrier systems that rely on the ability of chitosan to cross tight junctions and enhance particle uptake due to chitosan-specific mucoadhesive properties. Indeed, chitosan not only improves the adhesion of antigens to the mucosa promoting their absorption but also shows intrinsic immunostimulant abilities. Furthermore, by finely tuning the colloidal properties of chitosan, it can provide sustained antigen release to strongly activate the humoral defense. In the present review, we agnostically discuss the potential reasons why chitosan-based vaccine carriers, that efficiently elicit strong immune responses in experimental setups and in some pre-clinical/clinical studies, are still poorly considered for therapeutic formulations. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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22 pages, 2956 KiB  
Review
Nanoparticle-Based Adjuvants and Delivery Systems for Modern Vaccines
by Brankica Filipić, Ivana Pantelić, Ines Nikolić, Dragomira Majhen, Zorica Stojić-Vukanić, Snežana Savić and Danina Krajišnik
Vaccines 2023, 11(7), 1172; https://doi.org/10.3390/vaccines11071172 - 29 Jun 2023
Cited by 9 | Viewed by 3033
Abstract
Ever since the development of the first vaccine, vaccination has had the great impact on global health, leading to the decrease in the burden of numerous infectious diseases. However, there is a constant need to improve existing vaccines and develop new vaccination strategies [...] Read more.
Ever since the development of the first vaccine, vaccination has had the great impact on global health, leading to the decrease in the burden of numerous infectious diseases. However, there is a constant need to improve existing vaccines and develop new vaccination strategies and vaccine platforms that induce a broader immune response compared to traditional vaccines. Modern vaccines tend to rely on certain nanotechnology platforms but are still expected to be readily available and easy for large-scale manufacturing and to induce a durable immune response. In this review, we present an overview of the most promising nanoadjuvants and nanoparticulate delivery systems and discuss their benefits from tehchnological and immunological standpoints as well as their objective drawbacks and possible side effects. The presented nano alums, silica and clay nanoparticles, nanoemulsions, adenoviral-vectored systems, adeno-associated viral vectors, vesicular stomatitis viral vectors, lentiviral vectors, virus-like particles (including bacteriophage-based ones) and virosomes indicate that vaccine developers can now choose different adjuvants and/or delivery systems as per the requirement, specific to combatting different infectious diseases. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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39 pages, 2503 KiB  
Review
Vaccination Strategies Based on Bacterial Self-Assembling Proteins as Antigen Delivery Nanoscaffolds
by Félix Lamontagne, Vinay Khatri, Philippe St-Louis, Steve Bourgault and Denis Archambault
Vaccines 2022, 10(11), 1920; https://doi.org/10.3390/vaccines10111920 - 13 Nov 2022
Cited by 7 | Viewed by 3119
Abstract
Vaccination has saved billions of human lives and has considerably reduced the economic burden associated with pandemic and endemic infectious diseases. Notwithstanding major advancements in recent decades, multitude diseases remain with no available effective vaccine. While subunit-based vaccines have shown great potential to [...] Read more.
Vaccination has saved billions of human lives and has considerably reduced the economic burden associated with pandemic and endemic infectious diseases. Notwithstanding major advancements in recent decades, multitude diseases remain with no available effective vaccine. While subunit-based vaccines have shown great potential to address the safety concerns of live-attenuated vaccines, their limited immunogenicity remains a major drawback that still needs to be addressed for their use fighting infectious illnesses, autoimmune disorders, and/or cancer. Among the adjuvants and delivery systems for antigens, bacterial proteinaceous supramolecular structures have recently received considerable attention. The use of bacterial proteins with self-assembling properties to deliver antigens offers several advantages, including biocompatibility, stability, molecular specificity, symmetrical organization, and multivalency. Bacterial protein nanoassemblies closely simulate most invading pathogens, acting as an alarm signal for the immune system to mount an effective adaptive immune response. Their nanoscale architecture can be precisely controlled at the atomic level to produce a variety of nanostructures, allowing for infinite possibilities of organized antigen display. For the bottom-up design of the proteinaceous antigen delivery scaffolds, it is essential to understand how the structural and physicochemical properties of the nanoassemblies modulate the strength and polarization of the immune responses. The present review first describes the relationships between structure and the generated immune responses, before discussing potential and current clinical applications. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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