Toward Precision Adjuvants: Optimizing Science and Safety
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Purpose Of Review: The gradual replacement of inactivated whole cell and live attenuated vaccines with subunit vaccines has generally reduced reactogenicity but in many cases also immunogenicity. Although only used when necessary, adjuvants can be key to vaccine dose/antigen-sparing, broadening immune responses to variable antigens, and enhancing immunogenicity in vulnerable populations with distinct immunity. Licensed vaccines contain an increasing variety of adjuvants, with a growing pipeline of adjuvanted vaccines under development.
Recent Findings: Most adjuvants, including Alum, Toll-like receptor agonists and oil-in-water emulsions, activate innate immunity thereby altering the quantity and quality of an adaptive immune response. Adjuvants activate leukocytes, and induce mediators (e.g., cytokines, chemokines, and prostaglandin-E2) some of which are biomarkers for reactogenicity, that is, induction of local/systemic side effects. Although there have been safety concerns regarding a hypothetical risk of adjuvants inducing auto-immunity, such associations have not been established. As immune responses vary by population (e.g., age and sex), adjuvant research now incorporates principles of precision medicine. Innovations in adjuvant research include use of human in vitro models, immuno-engineering, novel delivery systems, and systems biology to identify biomarkers of safety and adjuvanticity.
Summary: Adjuvants enhance vaccine immunogenicity and can be associated with reactogenicity. Novel multidisciplinary approaches hold promise to accelerate and de-risk targeted adjuvant discovery and development. VIDEO ABSTRACT: http://links.lww.com/MOP/A53.
A synthetic cyclic peptide for promoting antigen presentation and immune activation.
Zhang J, Madge H, Mahmoud A, Lu L, Wang W, Huang W NPJ Vaccines. 2025; 10(1):9.
PMID: 39809901 PMC: 11733015. DOI: 10.1038/s41541-024-01050-4.
Singhal A, Taksande K Cureus. 2024; 16(9):e69880.
PMID: 39439610 PMC: 11494027. DOI: 10.7759/cureus.69880.
Rappuoli R, Alter G, Pulendran B Cell. 2024; 187(19):5171-5194.
PMID: 39303685 PMC: 11736809. DOI: 10.1016/j.cell.2024.07.021.
Soni D, Borriello F, Scott D, Feru F, DeLeon M, Brightman S Sci Adv. 2024; 10(27):eadg3747.
PMID: 38959314 PMC: 11221515. DOI: 10.1126/sciadv.adg3747.
Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro.
Schuller S, Barman S, Mendez-Giraldez R, Soni D, Daley J, Baden L Commun Biol. 2024; 7(1):709.
PMID: 38851856 PMC: 11162429. DOI: 10.1038/s42003-024-06390-4.