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Vaccines
Special Issues
Novel Adjuvants and Delivery Systems for Vaccines
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Novel Adjuvants and Delivery Systems for Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Design, Development, and Delivery".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 7720

Special Issue Editors

Dr. Christiane Chbib

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Larkin University, Miami, FL 33169, USA
Interests: vaccines; drug development; adjuvants; nanoparticle; quorum sensing; antibiotics; pre-clinical research
Dr. Mohammad N. Uddin

E-Mail Website
Guest Editor
College of Pharmacy, Mercer University, Atlanta, GA 30341, USA
Interests: vaccines; drug delivery; oral dissolving films
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Novel adjuvants and delivery systems for vaccines improve the quality of vaccine production by enhancing the immune response to a vaccine. Adjuvants can strengthen the immune system's response to the vaccine. Adjuvants have been traditionally used to increase the magnitude of the antibody response to a vaccine based on antibody titer or the ability to prevent infection and can guide the type of adaptive response to produce the most effective form of immunity. It is important to consider the construction of vaccine adjuvant delivery systems for both adjuvant activity and antigen delivery. In this Special Issue, we will explore prospective novel adjuvant approaches to modify innate and adaptive immune responses to ease the development of enhanced prophylactic or therapeutic vaccines. We welcome contributions to vaccine adjuvant advances, immune enhancement mechanisms, rational design, immunostimulatory molecules, emulsions, liposomes, virosomes, and polymers with functional molecules.

Dr. Christiane Chbib
Dr. Mohammad N. Uddin
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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

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

Keywords

  • vaccines
  • drug development
  • adjuvants
  • nanoparticle

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Published Papers (4 papers)

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Research

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16 pages, 2650 KB  
Article
Lipid Nanoparticle-Encapsulated PolyI:C as an Adjuvant Enhances Both Humoral and Cellular Immune Responses to the Hepatitis B Vaccine
by Zhixian Zhao, Bin Wang, Hao Wang, Qiang Zhang, Yunfei Liang and Yuan Liu
Vaccines 2026, 14(5), 397; https://doi.org/10.3390/vaccines14050397 - 29 Apr 2026
Viewed by 449
Abstract
Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine [...] Read more.
Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine performance. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA analog, activates TLR3/RLR pathways to enhance T-cell priming and cellular immunity. However, its utility as a sole adjuvant is limited by rapid nuclease degradation and poor cytosolic delivery. Lipid nanoparticles (LNPs), a mature delivery platform, enable high encapsulation efficiency, efficient cellular uptake, and endosomal escape. Objectives: This study aimed to evaluate the adjuvant effect of LNP-encapsulated PolyI:C (LNP-PolyI:C) on the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. Methods: The colloidal stability of LNP-PolyI:C stored at 2–8 °C for 9 months was monitored using dynamic light scattering (DLS) on a Zetasizer Lab instrument. Serum levels of HBsAg-specific IgG, IgG1, and IgG2a antibodies in immunized Kunming mice were measured by enzyme-linked immunosorbent assay (ELISA). The secretion of HBsAg-specific cytokines by splenocytes was analyzed using flow cytometry and enzyme-linked immunospot (ELISpot) assay. Results: The results demonstrated that the LNP-encapsulated PolyI:C adjuvant significantly increased the secretion of HBsAg-specific IFN-γ, IL-2, and TNF-α by splenocytes, indicating a Th1-biased and cytotoxic T lymphocyte (CTL)-mediated cellular immune response. In addition, this formulation markedly elevated serum titers of HBsAg-specific IgG, IgG1, and IgG2a. Conclusions: These findings underscore the advantages of the LNP-PolyI:C adjuvant in enhancing both humoral and cellular immunity, demonstrating its considerable potential as a novel adjuvant. Full article
(This article belongs to the Special Issue Novel Adjuvants and Delivery Systems for Vaccines)
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16 pages, 2036 KB  
Article
Adjuvanted Protein Vaccines Boost RNA-Based Vaccines for Broader and More Potent Immune Responses
by Jiho Kim, Jenn Davis, Bryan Berube, Malcolm Duthie, Sean A. Gray and Darrick Carter
Vaccines 2025, 13(8), 797; https://doi.org/10.3390/vaccines13080797 - 28 Jul 2025
Cited by 1 | Viewed by 2546
Abstract
Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent [...] Read more.
Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4TM, LiT4QTM, MiT4TM, and AlT4TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article
(This article belongs to the Special Issue Novel Adjuvants and Delivery Systems for Vaccines)
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Review

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33 pages, 1049 KB  
Review
Plant-Based Strategies for Vaccine Development: A Narrative Review of Recombinant Biofactories, Phytochemical Adjuvants, Innovative Delivery Systems, and Insights on Oral and Edible Vaccines
by Kianoosh Najafi, Maryam Jojani, Soroosh Najafi and Giovanni N. Roviello
Vaccines 2026, 14(5), 391; https://doi.org/10.3390/vaccines14050391 - 27 Apr 2026
Viewed by 982
Abstract
Background/Objectives: Vaccination is a critical public health intervention, yet its global implementation is hindered by high production costs and cold-chain requirements. This review aims to evaluate plant-based systems as sustainable, cost-efficient alternatives for vaccine production. Methods: A comprehensive literature search was conducted [...] Read more.
Background/Objectives: Vaccination is a critical public health intervention, yet its global implementation is hindered by high production costs and cold-chain requirements. This review aims to evaluate plant-based systems as sustainable, cost-efficient alternatives for vaccine production. Methods: A comprehensive literature search was conducted across major databases (PubMed, Scopus, Web of Science). The peer-reviewed references were critically assessed, focusing on molecular expression strategies, phytochemical immunomodulators, and plant-mediated oral delivery. Results: Plant and microalgae systems effectively support nuclear, chloroplast, and transient expression of diverse antigens. Furthermore, specific plant-derived compounds were found to act as potent adjuvants and immunostimulants, enhancing the immunogenicity of vaccine formulations. Edible plant tissues also provide a viable platform for oral delivery, reducing the need for extensive purification and refrigerated logistics. Conclusions: Integrating recombinant expression technologies with bioactive plant metabolites offers a flexible and scalable foundation for next-generation vaccines. These biological platforms show promise for addressing some immunization challenges, particularly in low-resource settings. Full article
(This article belongs to the Special Issue Novel Adjuvants and Delivery Systems for Vaccines)
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20 pages, 849 KB  
Review
Exploring the Biological Activities of Ionic Liquids and Their Potential to Develop Novel Vaccine Adjuvants
by Snehitha Akkineni, Mutasem Rawas-Qalaji, Samir A. Kouzi, Christiane Chbib and Mohammad N. Uddin
Vaccines 2025, 13(4), 365; https://doi.org/10.3390/vaccines13040365 - 28 Mar 2025
Cited by 6 | Viewed by 2604
Abstract
Ionic liquids (ILs) are salts with poorly coordinated ions, allowing them to exist in a liquid phase below 100 °C or at room temperature. Therefore, they are best described as room temperature ionic liquids (RTILs). In ionic liquids, the presence of a delocalized [...] Read more.
Ionic liquids (ILs) are salts with poorly coordinated ions, allowing them to exist in a liquid phase below 100 °C or at room temperature. Therefore, they are best described as room temperature ionic liquids (RTILs). In ionic liquids, the presence of a delocalized charge in at least one ion, coupled with an organic component, inhibits the establishment of a stable solid crystal lattice. Due to their flexible properties and several distinctive characteristics, such as high ionic conductivity, high solvation power, thermal stability, low volatility, and recyclability, ILs have been extensively used in chemical industries. In addition to their various other applications, they also hold potential for drug formulation development. Ionic liquids can be used as solubility enhancers, permeability enhancers, stabilizers, targeted delivery inducers, stealth property providers, or bioavailability enhancers. Moreover, ILs hold significant potential in vaccine formulation. Many new vaccines are in the pipeline with different types of antigens; however, the existence of only a limited number of adjuvants hinder their potential use. Thus, developing new, highly effective, low-cost adjuvant preparations is a central interest among formulation scientists. With their unique properties and biological functions, ILs can be highly promising candidates for new types of vaccines. Full article
(This article belongs to the Special Issue Novel Adjuvants and Delivery Systems for Vaccines)
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