Modern Adjuvants and Their Roles in Vaccine Development

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

Deadline for manuscript submissions: 20 February 2025 | Viewed by 7333

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Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
Interests: vaccine adjuvants and delivery platforms
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Dear Colleagues,

As you are aware, there is a lack of safe and potent adjuvants to aid in developing new and improved vaccines. Due to the uniqueness of each disease and the specific types of immune responses to be modulated, various kinds of adjuvants are needed to induce optimal immune responses against a particular disease. Vaccine adjuvants may also need to be tailored for use in different age groups due to the age-related differential immune responses to vaccines. In the past, adjuvant development has mainly relied on empirical experience, and only a few adjuvants have been approved for human use since the first(Alum) was discovered over 90 years ago. Significant advances have been made in the last three decades in understanding how adjuvants work. Modern techniques, such as high-throughput screening and in-silico screening, have also been used to discover novel adjuvants for human use. The last two decades have also seen increased investment in novel adjuvant development. These efforts are expected to accelerate novel adjuvant discovery and development. This Special Issue welcomes submissions of adjuvant discovery and development in diverse types of vaccines (e.g., subunit, mRNA-based) against infectious diseases, cancer, or immune-mediated diseases. This issue also welcomes submissions of adjuvant mechanism studies and explorations of combinatorial adjuvants in vaccine development.

Dr. Xinyuan Chen
Guest Editor

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Keywords

  • vaccine adjuvant
  • mechanism
  • combinatorial adjuvant
  • subunit
  • mRNA
  • vaccine discovery
  • vaccine development

Published Papers (4 papers)

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Research

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15 pages, 3419 KiB  
Article
Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by MF59 and AS03-like Adjuvants
by Jayachandra Reddy Nakkala, Yibo Li, Labone Akter, Xinliang Kang and Xinyuan Chen
Vaccines 2024, 12(5), 531; https://doi.org/10.3390/vaccines12050531 - 13 May 2024
Viewed by 841
Abstract
MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells [...] Read more.
MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms. Full article
(This article belongs to the Special Issue Modern Adjuvants and Their Roles in Vaccine Development)
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13 pages, 2608 KiB  
Article
Harnessing Pentameric Scaffold of Cholera Toxin B (CTB) for Design of Subvirion Recombinant Dengue Virus Vaccine
by Jemin Sung, Yucheol Cheong, Young-Seok Kim, Jina Ahn, Myung Hyun Sohn, Sanguine Byun and Baik-Lin Seong
Vaccines 2024, 12(1), 92; https://doi.org/10.3390/vaccines12010092 - 17 Jan 2024
Cited by 1 | Viewed by 1538
Abstract
Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based [...] Read more.
Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based approach, cholera toxin B (CTB) was harnessed as a structural scaffold for the five-fold symmetry of EDIII. Pivoted by an RNA-mediated chaperone for the protein folding and assembly, CTB-EDIII of dengue serotype 1 (DV1) was successfully produced as soluble pentamers in an E. coli host with a high yield of about 28 mg/L. Immunization of mice with CTB-DV1EDIII elicited increased levels of neutralizing antibodies against infectious viruses compared to the control group immunized with DV1EDIII without CTB fusion. IgG isotype switching into a balanced Th1/Th2 response was also observed, probably triggered by the intrinsic adjuvant activity of CTB. Confirming the immune-enhancing potential of CTB in stabilizing the pentamer assembly of EDIII, this study introduces a low-cost bacterial production platform designed to augment the soluble production of subunit vaccine candidates, particularly those targeting flaviviruses. Full article
(This article belongs to the Special Issue Modern Adjuvants and Their Roles in Vaccine Development)
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13 pages, 2434 KiB  
Article
Ginseng Polysaccharide Enhances the Humoral and Cellular Immune Responses to SARS-CoV-2 RBD Protein Subunit Vaccines
by Jing Zhang, Jing Feng, Yang Huang, Boyan Zhou, Bing Li and Rongxin Zhang
Vaccines 2023, 11(12), 1833; https://doi.org/10.3390/vaccines11121833 - 8 Dec 2023
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Abstract
The COVID-19 pandemic remarkably accelerated vaccine research progress. The role of adjuvants in enhancing vaccine immune intensity and influencing immune types has been considered. Ginseng polysaccharide (GPS) has been demonstrated to have strong immunoregulatory properties. It is important to explore the feasibility of [...] Read more.
The COVID-19 pandemic remarkably accelerated vaccine research progress. The role of adjuvants in enhancing vaccine immune intensity and influencing immune types has been considered. Ginseng polysaccharide (GPS) has been demonstrated to have strong immunoregulatory properties. It is important to explore the feasibility of adding GPS to vaccine adjuvant components to improve the immune response effect of RBD vaccines. Here, we prepared a SARS-CoV-2 RBD antigen using the Escherichia coli expression system and determined that subcutaneous administration of GPS at a dose of 40 mg/kg could effectively activate dendritic cells (DCs) and macrophages (MΦ) in mice. Compared with the RBD group, the RBD+GPS triggered stronger and persistent antibody responses. It is also notable that higher levels of RBD-specific IgG and IgA were distributed in the lungs of RBD+GPS-immunized BALB/c mice. In addition, the RBD+GPS also resulted in lower percentages of IFN-γ+ CD4+ T cells and higher percentages of IFN-γ+ CD8+ T cells and CD8+ Tcm cells. These results suggest that GPS could be a promising vaccine immuno-enhancer for SARS-CoV-2 RBD subunit vaccines to establish stronger systemic and pulmonary mucosal protective immunity. Full article
(This article belongs to the Special Issue Modern Adjuvants and Their Roles in Vaccine Development)
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Review

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28 pages, 2608 KiB  
Review
Advancements in Vaccine Adjuvants: The Journey from Alum to Nano Formulations
by Sivakumar S. Moni, Siddig Ibrahim Abdelwahab, Aamena Jabeen, Mohamed Eltaib Elmobark, Duaa Aqaili, Gassem Ghoal, Bassem Oraibi, Abdulla Mohammed Farasani, Ahmed Ali Jerah, Mahdi Mohammed A. Alnajai and Abdul Majeed Hamad Mohammad Alowayni
Vaccines 2023, 11(11), 1704; https://doi.org/10.3390/vaccines11111704 - 9 Nov 2023
Cited by 4 | Viewed by 3266
Abstract
Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in [...] Read more.
Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in reputable databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. The goal of this review is to provide a thorough analysis of the advances in the field of adjuvant research, to trace the evolution, and to understand the effects of the various adjuvants. Historically, alum was the pioneer in the field of adjuvants because it was the first to be approved for use in humans. It served as the foundation for subsequent research and innovation in the field. As science progressed, research shifted to identifying and exploiting the potential of newer adjuvants. One important area of interest is nano formulations. These advanced adjuvants have special properties that can be tailored to enhance the immune response to vaccines. The transition from traditional alum-based adjuvants to nano formulations is indicative of the dynamism and potential of vaccine research. Innovations in adjuvant research, particularly the development of nano formulations, are a promising step toward improving vaccine efficacy and safety. These advances have the potential to redefine the boundaries of vaccination and potentially expand the range of diseases that can be addressed with this approach. There is an optimistic view of the future in which improved vaccine formulations will contribute significantly to improving global health outcomes. Full article
(This article belongs to the Special Issue Modern Adjuvants and Their Roles in Vaccine Development)
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