Aluminium Adjuvants – A Nanomaterial used as Adjuvants in Human Vaccines for Decades

Background:Aluminium salts have been used for decades in vaccines as adjuvants to facilitate the adaptive immune response against co-administered antigens. Two types of aluminium adjuvant are mostly used, aluminium oxyhydroxide and aluminium hydroxyphosphate. Both types of aluminium adjuvant consist of nanoparticles that form loose, micrometre sized aggregates at circumneutral pH.Aluminium adjuvants constitute a well-documented example of administration of nanomaterials to humans with infrequent side effects and a safety record generally regarded as excellent. However, despite its prolonged use in human and veterinary medicine, the mechanisms behind the enhanced response and the immune stimulatory effect are still by and large unknown.Methods:The present paper reviews existing ideas regarding the immunostimulatory effects of aluminium adjuvants, with a focus on the induction of an inflammatory response by cellular stress. Reviewed information was obtained from peer-reviewed scientific papers published in 1988 to date with one exception, a paper published 1931.Results:Cellular stress causes extra cellular signalling of Danger Associated Molecular Patterns (DAMPs) and upon phagocytosis of aluminium adjuvants the cells need to manage the ingested particles.Conclusion:A persistent intracellular accumulation of aluminium adjuvants will be a solid depository of sparingly soluble aluminium salts maintaining a constant concentration of Al3+ions in the cytoplasm and this will affect multiple biochemical processes. The cell will be under constant stress and DAMP signalling will occur and we would like to suggest the maintenance of a constant concentration Al3+ions in the cytoplasm as a general underlying feature of the immune stimulation properties of aluminium adjuvants.

Download Full-text

Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

Journal of Materials Chemistry B ◽

10.1039/d1tb00397f ◽

2021 ◽

Author(s):

Suah Yang ◽

In-Cheol Sun ◽

Hee Sook Hwang ◽

Man Kyu Shim ◽

Hong Yeol Yoon ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Cancer Immunotherapy ◽

Potential Application ◽

Adaptive Immune Response ◽

Immunogenic Cell Death ◽

Living Body ◽

Adaptive Immune ◽

Physical Stimuli ◽

Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

Download Full-text

Toll-like receptors and diabetes: a therapeutic perspective

Clinical Science ◽

10.1042/cs20110357 ◽

2011 ◽

Vol 122 (5) ◽

pp. 203-214 ◽

Cited By ~ 63

Author(s):

Mohan R. Dasu ◽

Sandra Ramirez ◽

Roslyn R. Isseroff

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Adaptive Immune Response ◽

Innate Immune ◽

Undiagnosed Diabetes ◽

Innate Immune Responses ◽

Toll Like Receptors ◽

Adaptive Immune ◽

Molecular Patterns ◽

Therapeutic Perspective

Diabetes is a mutifactorial metabolic disorder that leads to a number of complications. Diabetes is estimated to affect 36 million people in the U.S.A., and the prevalence of diagnosed and undiagnosed diabetes is at 9.3% and continues to rise. Evidence from experimental animal models as well as humans has indicated that systemic inflammation plays a role in the pathophysiological processes of diabetes and is facilitated by innate immune responses. TLRs (Toll-like receptors) are key innate immune receptors that recognize conserved PAMPs (pathogen-associated molecular patterns), induce inflammatory responses essential for host defences and initiate an adaptive immune response. Although TLR expression is increased in a plethora of inflammatory disorders, the effects of metabolic aberrations on TLRs and their role in diabetes and its complications is still emerging. In the present paper, we provide a systematic review on how TLRs play a detrimental role in the pathogenic processes [increased blood sugar, NEFAs (non-esterified ‘free’ fatty acids), cytokines and ROS (reactive oxygen species)] that manifest diabetes. Furthermore, we will highlight some of the therapeutic strategies targeted at decreasing TLRs to abrogate inflammation in diabetes that may eventually result in decreased complications.

Download Full-text

Host–pathogen interactions in the critically ill

10.1093/med/9780199600830.003.0306 ◽

2016 ◽

Author(s):

Guillaume Geri ◽

Jean-Paul Mira

Keyword(s):

Immune Response ◽

Genetic Variability ◽

Adaptive Immune Response ◽

Genomic Analysis ◽

Initial Contact ◽

Adaptive Immune ◽

Cytokines And Chemokines ◽

Pathogen Diversity ◽

Host Genetic ◽

Molecular Patterns

Infection by a pathogenic micro-organism triggers a coordinated activation of both innate and adaptive immune responses. The innate immune response quickly triggers an antimicrobial response that will initiate development of a pathogen-specific, long-lasting adaptive immune response. Accurate recognition of microbial-associated molecular patterns by pattern-recognition receptors (PRRs) is the cornerstone of this immediate response. Most studied PRRs are Toll-like receptors (TLRs) and their kinase signalling cascades that activate nuclear transcription factors, and induce gene expression and cytokine production. Deficiencies or genetic variability in these different signalling pathways may lead to recurrent pyogenic infections and severe invasive diseases. After initial contact between the host and pathogen, numerous factors mediate the inflammatory response, as pro-inflammatory cytokines and chemokines. Apart from host genetic variability, pathogen diversity also influences the phenotypic features of various infectious diseases. Genomic analysis may assist in the development of targeted therapies or new therapeutic strategies based on both patient and microorganism genotype.

Download Full-text

Toll-like receptors as a therapeutic target in cancer, infections and inflammatory diseases

Immunotherapy ◽

10.2217/imt-2019-0096 ◽

2020 ◽

Vol 12 (5) ◽

pp. 311-322

Author(s):

Lizdany Flórez-Álvarez ◽

Lanie Ruiz-Perez ◽

Natalia Taborda ◽

Juan C Hernandez

Keyword(s):

Immune Response ◽

Immune Responses ◽

Inflammatory Diseases ◽

Adaptive Immune Response ◽

Treatment Strategies ◽

Toll Like Receptors ◽

Tumor Treatment ◽

Special Report ◽

Adaptive Immune ◽

Molecular Patterns

Toll-like receptors (TLRs) are widely expressed pattern recognition receptors that bind to conserved molecular patterns expressed by pathogens and damaged cells. After recognition, activated TLRs induce the expression of various proinflammatory and antiviral molecules. Thus, TLRs are potential targets for treatment strategies aimed at boosting the adaptive immune response to vaccines, controlling infections, enhancing immune responses during tumor treatment and attenuating immune responses in inflammatory disorders. This Special Report examines the potential of TLRs as targets for the treatment of cancer, infections and inflammatory diseases. Here, we make a particular emphasis on molecules capable of modulating TLRs and their therapeutic applications.

Download Full-text

Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2019.21.1/vaharoutunian ◽

2019 ◽

Vol 21 (1) ◽

pp. 7-19 ◽

Cited By ~ 1

Keyword(s):

Alzheimer Disease ◽

Cognitive Aging ◽

Oldest Old ◽

Adaptive Immune Response ◽

Effector T Cells ◽

Immune Defense ◽

Supporting Evidence ◽

Therapeutic Approaches ◽

Related Data ◽

Adaptive Immune

Multifaceted evidence supports the hypothesis that inflammatory-immune mechanisms contribute to Alzheimer disease (AD) neuropathology and genetic association of several immune specific genes (TREM2, CR1, and CD33) suggests that maladaptive immune responses may be pivotal drivers of AD pathogenesis. We reviewed microglia-related data from postmortem AD studies and examined supporting evidence from AD animal models to answer the following questions: i) What is the temporal sequence of immune activation in AD progression and what is its impact on cognition? ii) Are there discordant, "primed", microglia responses in AD vs successful cognitive aging? iii) Does central nervous system (CNS) repair in aging depend on recruitment of the elements of cellular adaptive immune response such as effector T cells, and can the recruitment of systemic immune cells ameliorate AD neuropathology? iv) How effective are the immune-system-based therapeutic approaches currently employed for the treatment of AD?

Download Full-text