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Pharmaceutics
Special Issues
Designing and Developing the Next Generation of Vaccine Adjuvants
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Designing and Developing the Next Generation of Vaccine Adjuvants

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 20796

Special Issue Editors

Dr. Derek T. O'Hagan

E-Mail Website
Guest Editor
GSK, Rockville Center for Vaccines Research, Rockville, MD 20850, USA
Interests: adjuvants; vaccine development
Dr. Rushit N. Lodaya

E-Mail Website
Guest Editor
GSK, Rockville Center for Vaccines Research, Rockville, MD 20850, USA
Interests: adjuvants; vaccine development

Special Issue Information

Dear Colleagues,

Over the past two decades, there have been significant advances in the development of novel vaccine adjuvant formulations, building from an improved understanding of how these adjuvants work, and the key role of ‘delivery’. In addition to the established insoluble aluminum salts and emulsion adjuvants, this past decade also saw the advance of several new adjuvants into clinical development, and even included into licensed products. These recent advances have expanded our understanding on mechanisms of action and have laid the groundwork for the development of new and improved technologies. There have been significant insights into the identification of new and improved agonists, which can be exploited for the rational development of the next generation of adjuvants—particularly if these ligands can be coupled with improved delivery systems to enhance potency, and limit reactogenicity, or safety concerns. This Special Issue on “Designing and Developing the Next Generation of Vaccine Adjuvants” will focus on highlighting key tools for designing and discovering novel vaccine adjuvants as well as discussing advances made in developing adjuvants suitable for clinical evaluation.

Dr. Derek T. O'Hagan
Dr. Rushit N. Lodaya
Guest Editors

Manuscript Submission Information

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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

  • adjuvant systems
  • immune potentiators
  • immunomodulators
  • toll-like receptor (TLR) agonists
  • emulsions
  • aluminum salts
  • nanoparticles
  • polymers

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Published Papers (5 papers)

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Review

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24 pages, 1352 KiB  
Review
Aluminum Adjuvants—‘Back to the Future’
by Donatello Laera, Harm HogenEsch and Derek T. O’Hagan
Pharmaceutics 2023, 15(7), 1884; https://doi.org/10.3390/pharmaceutics15071884 - 4 Jul 2023
Cited by 44 | Viewed by 8573
Abstract
Aluminum-based adjuvants will continue to be a key component of currently approved and next generation vaccines, including important combination vaccines. The widespread use of aluminum adjuvants is due to their excellent safety profile, which has been established through the use of hundreds of [...] Read more.
Aluminum-based adjuvants will continue to be a key component of currently approved and next generation vaccines, including important combination vaccines. The widespread use of aluminum adjuvants is due to their excellent safety profile, which has been established through the use of hundreds of millions of doses in humans over many years. In addition, they are inexpensive, readily available, and are well known and generally accepted by regulatory agencies. Moreover, they offer a very flexible platform, to which many vaccine components can be adsorbed, enabling the preparation of liquid formulations, which typically have a long shelf life under refrigerated conditions. Nevertheless, despite their extensive use, they are perceived as relatively ‘weak’ vaccine adjuvants. Hence, there have been many attempts to improve their performance, which typically involves co-delivery of immune potentiators, including Toll-like receptor (TLR) agonists. This approach has allowed for the development of improved aluminum adjuvants for inclusion in licensed vaccines against HPV, HBV, and COVID-19, with others likely to follow. This review summarizes the various aluminum salts that are used in vaccines and highlights how they are prepared. We focus on the analytical challenges that remain to allowing the creation of well-characterized formulations, particularly those involving multiple antigens. In addition, we highlight how aluminum is being used to create the next generation of improved adjuvants through the adsorption and delivery of various TLR agonists. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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18 pages, 1542 KiB  
Review
Practical Considerations for Next-Generation Adjuvant Development and Translation
by William R. Lykins and Christopher B. Fox
Pharmaceutics 2023, 15(7), 1850; https://doi.org/10.3390/pharmaceutics15071850 - 29 Jun 2023
Cited by 4 | Viewed by 3783
Abstract
Over the last several years, there has been increased interest from academia and the pharmaceutical/biotech industry in the development of vaccine adjuvants for new and emerging vaccine modalities. Despite this, vaccine adjuvant development still has some of the longest timelines in the pharmaceutical [...] Read more.
Over the last several years, there has been increased interest from academia and the pharmaceutical/biotech industry in the development of vaccine adjuvants for new and emerging vaccine modalities. Despite this, vaccine adjuvant development still has some of the longest timelines in the pharmaceutical space, from discovery to clinical approval. The reasons for this are manyfold and range from complexities in translation from animal to human models, concerns about safety or reactogenicity, to challenges in sourcing the necessary raw materials at scale. In this review, we will describe the current state of the art for many adjuvant technologies and how they should be approached or applied in the development of new vaccine products. We postulate that there are many factors to be considered and tools to be applied earlier on in the vaccine development pipeline to improve the likelihood of clinical success. These recommendations may require a modified approach to some of the common practices in new product development but would result in more accessible and practical adjuvant-containing products. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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15 pages, 3888 KiB  
Review
Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations
by Branden Lee, Etsuro Nanishi, Ofer Levy and David J. Dowling
Pharmaceutics 2023, 15(6), 1766; https://doi.org/10.3390/pharmaceutics15061766 - 19 Jun 2023
Cited by 6 | Viewed by 2658
Abstract
Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic [...] Read more.
Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic and mechanistic differences in the immune systems of diverse vulnerable populations, emerging research in precision vaccine discovery and development has explored how to optimize immunizations across the lifespan. Here, we focus on two key elements of precision vaccinology, as applied to epidemic/pandemic response and preparedness, including (a) selecting robust combinations of adjuvants and antigens, and (b) coupling these platforms with appropriate formulation systems. In this context, several considerations exist, including the intended goals of immunization (e.g., achieving immunogenicity versus lessening transmission), reducing the likelihood of adverse reactogenicity, and optimizing the route of administration. Each of these considerations is accompanied by several key challenges. On-going innovation in precision vaccinology will expand and target the arsenal of vaccine components for protection of vulnerable populations. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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Other

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9 pages, 990 KiB  
Opinion
Head-to-Head Comparison of Novel Vaccine Technologies Comes with a Minefield of Challenges
by Dennis Christensen
Pharmaceutics 2024, 16(1), 12; https://doi.org/10.3390/pharmaceutics16010012 - 20 Dec 2023
Cited by 1 | Viewed by 1847
Abstract
Modern vaccine development is having a golden period, with a variety of novel subunit technologies being introduced into clinical development in recent years. This opens the opportunity to find the best platform to use for novel vaccine antigen candidates through head-to-head comparative studies. [...] Read more.
Modern vaccine development is having a golden period, with a variety of novel subunit technologies being introduced into clinical development in recent years. This opens the opportunity to find the best platform to use for novel vaccine antigen candidates through head-to-head comparative studies. Seldom appreciated is, however, the fact that these different technologies often do not have the same optimal antigen dose ratio, prime-boost regime and peak timepoint for measuring immunity. Instead, the preclinical studies that make the basis for platform selection use standard protocols not optimized for individual vaccines and fail to make selection on an informed basis. Here, I discuss the opportunities we have to optimize vaccine platform technologies through a better understanding of vaccine priming kinetics, the optimal antigen dose and sampling time and location. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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17 pages, 2256 KiB  
Perspective
Next-Generation Adjuvants: Applying Engineering Methods to Create and Evaluate Novel Immunological Responses
by Jeremiah Y. Kim, Matthew G. Rosenberger, Nakisha S. Rutledge and Aaron P. Esser-Kahn
Pharmaceutics 2023, 15(6), 1687; https://doi.org/10.3390/pharmaceutics15061687 - 8 Jun 2023
Cited by 6 | Viewed by 3053
Abstract
Adjuvants are a critical component of vaccines. Adjuvants typically target receptors that activate innate immune signaling pathways. Historically, adjuvant development has been laborious and slow, but has begun to accelerate over the past decade. Current adjuvant development consists of screening for an activating [...] Read more.
Adjuvants are a critical component of vaccines. Adjuvants typically target receptors that activate innate immune signaling pathways. Historically, adjuvant development has been laborious and slow, but has begun to accelerate over the past decade. Current adjuvant development consists of screening for an activating molecule, formulating lead molecules with an antigen, and testing this combination in an animal model. There are very few adjuvants approved for use in vaccines, however, as new candidates often fail due to poor clinical efficacy, intolerable side effects, or formulation limitations. Here, we consider new approaches using tools from engineering to improve next-generation adjuvant discovery and development. These approaches will create new immunological outcomes that will be evaluated with novel diagnostic tools. Potential improved immunological outcomes include reduced vaccine reactogenicity, tunable adaptive responses, and enhanced adjuvant delivery. Evaluations of these outcomes can leverage computational approaches to interpret “big data” obtained from experimentation. Applying engineering concepts and solutions will provide alternative perspectives, further accelerating the field of adjuvant discovery. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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