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Emerging concepts in the science of vaccine adjuvants.
Pulendran, B, S Arunachalam, P, O'Hagan, DT
Nature reviews. Drug discovery. 2021;(6):454-475
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Abstract
Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.
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Glycophosphopeptical AM3 Food Supplement: A Potential Adjuvant in the Treatment and Vaccination of SARS-CoV-2.
Fernández-Lázaro, D, Fernandez-Lazaro, CI, Mielgo-Ayuso, J, Adams, DP, García Hernández, JL, González-Bernal, J, González-Gross, M
Frontiers in immunology. 2021;:698672
Abstract
The world is currently experiencing the coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-2 (SARS-CoV-2). Its global spread has resulted in millions of confirmed infections and deaths. While the global pandemic continues to grow, the availability of drugs to treat COVID-19 infections remains limited to supportive treatments. Moreover, the current speed of vaccination campaigns in many countries has been slow. Natural substrates with biological immunomodulatory activity, such as glucans, may represent an adjuvant therapeutic agent to treat SARS-CoV-2. AM3, a natural glycophosphopeptical, has previously been shown to effectively slow, with no side effects, the progression of infectious respiratory diseases by regulating effects on innate and adaptive immunity in experimental models. No clinical studies, however, exist on the use of AM3 in SARS-CoV-2 infected patients. This review aims to summarize the beneficial effects of AM3 on respiratory diseases, the inflammatory response, modulation of immune response, and attenuation of muscle. It will also discuss its potential effects as an immune system adjuvant for the treatment of COVID-19 infections and adjuvant for SARS-CoV-2 vaccination.
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Host sphingolipids: Perspective immune adjuvant for controlling SARS-CoV-2 infection for managing COVID-19 disease.
Prakash, H, Upadhyay, D, Bandapalli, OR, Jain, A, Kleuser, B
Prostaglandins & other lipid mediators. 2021;:106504
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Abstract
Sphingolipids are potent bioactive agents involved in the pathogenesis of various respiratory bacterial infections. To date, several sphingolipid derivatives are known, but S1P (Sphingosine-1-phosphate) and Ceramide are the best-studied sphingolipid derivatives in the context of human diseases. These are membrane-bound lipids that influence host-pathogen interactions. Based on these features, we believe that sphingolipids might control SARS-CoV-2 infection in the host. SARS-CoV-2 utilizes the ACE-II receptor (Angiotensin-converting enzyme II receptor) on epithelial cells for its entry and replication. Activation of the ACE-II receptor is indirectly associated with the activation of S1P Receptor 1 signaling which is associated with IL-6 driven fibrosis. This is expected to promote pathological responses during SARS-CoV-2 infection in COVID-19 cases. Given this, mitigating S1P signaling by application of either S1P Lyase (SPL) or S1P analog (Fingolimod / FTY720) seems to be potential approach for controlling these pathological outcomes. However, due to the immunosuppressive nature of FTY720, it can modulate hyper-inflammatory responses and only provide symptomatic relief, which may not be sufficient for controlling the novel COVID-19 infection. Since Th1 effector immune responses are essential for the clearance of infection, we believe that other sphingolipid derivatives like Cermaide-1 Phosphate with antiviral potential and adjuvant immune potential can potentially control SARS-CoV-2 infection in the host by its ability in enhancing autophagy and antigen presentation by DC to promote T cell response which can be helpful in controlling SARS-CoV-2 infection in novel COVID-19 patients.