Novel Adjuvants: The Immunoregulation Effect, Molecular Mechanisms, and Utilization

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About this Research Topic

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Background

Adjuvants are vaccine components that enhance the magnitude, breadth, and durability of the immune response. Most modern vaccines are designed to have limited vaccine antigens, such as components of pathogenic microorganisms and recombinant molecules (proteins or nucleic acids) in order to reduce the risk of side effects. To compensate for the low efficacy resulting from the limited immunogenicity of antigens, many vaccine products are required to contain effective adjuvants. Following its introduction in the 1920s, there are only the alum and other five adjuvants licensed for human vaccination although their molecular mechanisms by which these adjuvants work remain only partially understood.

Nowadays, the latest understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is increasingly facilitating the exploration and development of stronger and better adjuvants for both animal and human vaccines. Recent basic advances inspire that tissue damage, different forms of cell death, and metabolic and nutrient sensors could be employed to modulate the innate immune system to activate adaptive immunity. Moreover, novel conceptual discoveries in systems biology highlight the molecular networks driving immune response to vaccines (‘systems vaccinology’), which provide the mechanistic insights and guidance to speed up the vaccine discovery and development process. This will satisfy the urgent need for control of new emerging infectious diseases, such as Covid-19 and tuberculosis.

The goal of this Research Topic on adjuvants is to provide a forum to promote the academic exchange about research on the regulation of activation of innate immunity, adaptive immune response process, immune memory, and immunoprotection of animals and humans to vaccination by use of adjuvants. It focuses on revealing how to explore the novel adjuvants, discussing their potential effects on vaccinations, and highlighting how to develop safer and more competent adjuvants. Based on the latest immunology advances and system vaccinology, we welcome manuscripts in the following subtopics:

1. Stimulation of immune cells by new molecules from the Danger model and their derivatives, including agonists of PRRs, damage-associated molecular patterns (DAMPs), and cell death via necroptosis or pyroptosis as well as other stress signals such as amino acid starvation (via ancient stress and nutrient-sensing pathways). The possible synergic effects among these stimuli on Toll-like receptors (TLRs), innate PRRs (such as retinoic acid-inducible gene I (RIG-I) and other RNA sensors), DNA sensors (such as stimulator of interferon genes (STING) protein), C-type lectins, nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and cytosolic receptors —such as NLRP3.

2. Approaches of targeting DCs/APCs to promote uptake of antigens, activation of adaptive competent immune cells.

3. Use of the molecular networks and insights from systems vaccinology acquire more accurate and comprehensive regulation of innate and adaptive immune responses to result in stronger immunity and longer protection duration, such as designing novel adjuvants, metabolites, small molecules immune potentiators (SMIPs), synthetic ligands and cytokines allowing targeting subsets of adaptive competent immune cells and precision modulation and orchestrating continuous education to B and T cells, which lead to better proliferation, differentiation and maturation of immune memory and effectors to induce sustained protective immunity.

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